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1
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Boiko JR, Hill GR. Chronic Graft-versus-host Disease: Immune Insights, Therapeutic Advances, and Parallels for Solid Organ Transplantation. Transplantation 2025; 109:955-966. [PMID: 39682018 PMCID: PMC12097962 DOI: 10.1097/tp.0000000000005298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
Chronic graft-versus-host disease (cGVHD) remains a frequent and morbid outcome of allogeneic hematopoietic cell transplantation (HCT), in which the donor-derived immune system attacks healthy recipient tissue. Preceding tissue damage mediated by chemoradiotherapy and alloreactive T cells compromise central and peripheral tolerance mechanisms, leading to aberrant donor T cell and germinal center B cell differentiation, culminating in pathogenic macrophage infiltration and differentiation in target tissue, with ensuant fibrosis. This process results in a heterogeneous clinical syndrome with significant morbidity and mortality, frequently requiring prolonged therapy. In this review, we discuss the processes that interrupt immune tolerance, the subsequent clinical manifestations, and new FDA-approved therapeutic approaches that have been born from a greater understanding of disease pathogenesis in preclinical systems, linking to parallel processes following solid organ transplantation.
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Affiliation(s)
- Julie R. Boiko
- Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
- Department of Pediatrics, University of Washington, Seattle, WA
| | - Geoffrey R. Hill
- Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
- Department of Medicine, University of Washington, Seattle, WA
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Beer SA, Blättel J, Reuß K, Maier CP, Faul C, Vogel W, Bethge W, Lengerke C. Long-term patient-reported outcomes following allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2025; 60:617-624. [PMID: 40011659 PMCID: PMC12061752 DOI: 10.1038/s41409-025-02540-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 01/22/2025] [Accepted: 02/18/2025] [Indexed: 02/28/2025]
Abstract
Therapeutic progress has improved the overall survival of patients treated with allogeneic hematopoietic cell transplantation (alloHCT). Thus, the impact on quality of life (QoL) becomes increasingly relevant. However, QoL is not monitored regularly in clinical practice, and most trials stop QoL assessments early post-alloHCT, missing long-term dynamics. To address this knowledge gap, we conducted a cross-sectional survey of 214 adult alloHCT recipients (average age 53 y, 42.5% female, median follow-up 56 months) to evaluate QoL using patient-reported outcome measurements (PROMs), spanning a period from 30 days to over 10 years post-transplant. Participants completed the EORTC QLQ-C30 and FACT-BMT at a single follow-up timepoint to investigate QoL-related factors. Comparing long-term follow-up patients (beyond year 3, n = 125) with short-term follow-up patients (day 30 to month 12, n = 89) shows significantly better long-term QoL outcomes (P = 0.016). However, PROM symptom scales indicate moderate fatigue and insomnia rates in long-term survivors. Better QoL was associated with male gender, lower ECOG, RIC conditioning, no relapse, no ongoing immunosuppression and full-time work. Summarized, while we observe encouraging long-term outcomes, our data suggest that QoL recovery remain highly individual. We strongly recommend the use of PROMs to enhance our understanding of long-term survivorship post-alloHCT.
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Affiliation(s)
- Sina Alexandra Beer
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
| | - Johanna Blättel
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
| | - Kristina Reuß
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
| | - Claus-Philipp Maier
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
- Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tübingen, Tübingen, Germany
| | - Christoph Faul
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
| | - Wichard Vogel
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
| | - Wolfgang Bethge
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
| | - Claudia Lengerke
- Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
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Vovk N, Urek M, Cankar K, Nemeth L. Oral Health-Related Quality of Life After Allogeneic Bone Marrow Transplant-A Cross-Sectional Study. Healthcare (Basel) 2025; 13:561. [PMID: 40077124 PMCID: PMC11899322 DOI: 10.3390/healthcare13050561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/27/2025] [Accepted: 03/02/2025] [Indexed: 03/14/2025] Open
Abstract
Objectives: The aim of this study was to evaluate the oral health-related quality of life of patients with chronic graft-versus-host disease. Methods: A total of 22 patients with graft-versus-host disease aged 45.05 ± 14.66 years were enrolled in a single-centre cross-sectional study. Data from questionnaires on general health and diet, clinical examinations, and salivary tests were used to assess caries risks using the Cariogram computer programme. The Slovenian version of the Oral Health Impact Profile Questionnaire (OHIP-SVN) was used to determine the oral health-related quality of life. Results: Compared to healthy individuals, patients with chronic graft-versus-host disease had a lower oral health-related quality of life and a lower stimulated salivary flow rate (in both cases p < 0.001). The OHIP summary score correlated with stimulated salivary pH (R = 0.4916, p = 0.0277) and caries risk (R = 0.5420, p = 0.0111). Conclusions: In conclusion, our results confirm that cGVHD has a negative impact on oral health-related quality of life due to lower stimulated salivary pH and elevated caries risk (reduced salivary pH, flow rate, buffering capacity, and elevated Streptococcus mutans and Lactobacillus bacteria count). These findings emphasise the importance of a comprehensive assessment of oral health and preventive care in patients with cGVHD and suggest that the integration of clinical and quality of life measures could lead to improved patient care strategies.
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Affiliation(s)
- Nina Vovk
- Department of Dental Diseases and Normal Dental Morphology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;
| | - Manca Urek
- Dental Center Osovnikar, 4220 Škofja Loka, Slovenia;
| | - Ksenija Cankar
- Institute of Physiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;
| | - Lidija Nemeth
- Department of Dental Diseases and Normal Dental Morphology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;
- Division of Stomatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
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Albanyan O, Elmariah H, Kalos D, Kim J, Faramand R, Sallman D, Mishra A, Sweet K, Perez L, Ochoa-Bayona J, Nieder M, Komrokji R, Lancet J, Fernandez H, Nishihori T, Pidala J, Anasetti C, Bejanyan N. Melphalan Dose in Combination With Fludarabine Affects Gastrointestinal Toxicity and Graft-Versus-Host Disease After Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndromes. Transplant Cell Ther 2024; 30:1090.e1-1090.e10. [PMID: 39147136 DOI: 10.1016/j.jtct.2024.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 07/21/2024] [Accepted: 08/07/2024] [Indexed: 08/17/2024]
Abstract
Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m2 (Mel-100, n = 62) versus 140 mg/m2 (Mel-140, n = 283) in combination with Flu. Median age at allo-HCT was 66 years and median follow-up was 36.5 months. For Mel-100 versus Mel-140 groups, any grade gastrointestinal (GI) toxicity rates were 40.3% versus 67.8% (P < .001), day 100 grade II to IV acute graft-versus-host disease (GVHD) rates were 21.0% versus 43.1% (P = .001) and 2-year chronic GVHD rates were 17.4% versus 27.1% (P = .033). In multivariable analysis, Mel-140 resulted in higher risks of GI toxicity (HR = 1.83, P = .013), grade II to IV acute GVHD (HR=2.35, P = .003), and moderate/severe chronic GVHD (HR = 3.13, P = .007). Total Mel dose had no independent impact on oral mucositis, nonrelapse mortality, relapse, relapse-free survival, and overall survival. While independent validation of our observation is warranted, our findings support using Mel-100 in combination with Flu to minimize allo-HCT toxicities and morbidities related to GVHD.
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Affiliation(s)
- Omar Albanyan
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida; Department of Hematology and Stem Cell Transplant, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Hany Elmariah
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Denise Kalos
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida
| | - Jongphil Kim
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida
| | - Rawan Faramand
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - David Sallman
- Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida
| | - Asmita Mishra
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Kendra Sweet
- Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida
| | - Lia Perez
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Jose Ochoa-Bayona
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Michael Nieder
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Rami Komrokji
- Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida
| | - Jeffery Lancet
- Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida
| | - Hugo Fernandez
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Taiga Nishihori
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Joseph Pidala
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Claudio Anasetti
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida
| | - Nelli Bejanyan
- Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida.
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5
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Visintini C, Lucchetta C, Venturini M, Mansutti I, Chiappinotto S, Patriarca F, Palese A. Perspective on oral medication adherence among patients with acute graft-versus-host disease: a qualitative descriptive study. Support Care Cancer 2024; 32:633. [PMID: 39230629 PMCID: PMC11374915 DOI: 10.1007/s00520-024-08825-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 08/18/2024] [Indexed: 09/05/2024]
Abstract
PURPOSE Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD. METHODS A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed. RESULTS Participants aged 25-74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: "Transiting from an external obligation to a habit"; "Being in the middle between the negative and positive effects of the IMMs"; "Failure to systematically respect the rules"; and "Adopting personal strategies to become adherent". After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules. CONCLUSIONS MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients' MA to IMMs.
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Affiliation(s)
- Chiara Visintini
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Montpellier's Street, 1, 00133, Rome, Italy.
- Haematology and Stem Cell Transplantation Unit, Udine University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.
| | - Chiara Lucchetta
- Oncology Unit, Udine University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | | | - Irene Mansutti
- Department of Medicine, University of Udine, Udine, Italy
| | | | - Francesca Patriarca
- Haematology and Stem Cell Transplantation Unit, Udine University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
- Department of Medicine, University of Udine, Udine, Italy
| | - Alvisa Palese
- Department of Medicine, University of Udine, Udine, Italy
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Lahijani S, Rueda-Lara M, McAndrew N, Nelson AM, Guo M, Knight JM, Wiener L, Miran DM, Gray TF, Keane EP, Yek MH, Sannes TS, Applebaum AJ, Fank P, Babu P, Pozo-Kaderman C, Amonoo HL. A Biobehavioral Perspective on Caring for Allogeneic Hematopoietic Stem Cell Transplant Survivors with Graft-Versus-Host Disease. Transplant Cell Ther 2024; 30:S493-S512. [PMID: 39370233 DOI: 10.1016/j.jtct.2024.05.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 05/25/2024] [Indexed: 10/08/2024]
Abstract
Among the potential complications of allogeneic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) is common and associated with significant physical and psychosocial symptom burden. Despite substantial advances in GVHD treatment, the global immune suppression that frequently accompanies GVHD treatment also contributes to high rates of physical and emotional suffering and mortality. The complex manifestations of GVHD and its treatment warrant a multidisciplinary team-based approach to managing patients' multi-organ system comorbidities. A biobehavioral framework can enhance our understanding of the complex association between medications, physical symptoms, and psychosocial distress in patients with GVHD. Hence, for this perspective, we highlight the importance of addressing both the physical and psychosocial needs experienced by patients with GVHD and provide guidance on how to approach and manage those symptoms and concerns as part of comprehensive cancer care.
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Affiliation(s)
- Sheila Lahijani
- Department of Psychiatry, Stanford University School of Medicine and Stanford Cancer Center Psychosocial Oncology Program, Stanford, California
| | - Maria Rueda-Lara
- Department of Psychiatry, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Natalie McAndrew
- School of Nursing, College of Health Professions and Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin; Department of Patient Care Research, Froedtert & The Medical College of Wisconsin, Froedtert Hospital, Milwaukee, Wisconsin
| | - Ashley M Nelson
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Michelle Guo
- Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts
| | - Jennifer M Knight
- Departments of Psychiatry, Medicine, and Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Lori Wiener
- Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland
| | - Damien M Miran
- Harvard Medical School, Boston, Massachusetts; Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Tamryn F Gray
- Harvard Medical School, Boston, Massachusetts; Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts; Phyllis F. Cantor Center for Research in Nursing and Patient Care Services, Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Stem Cell Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Palliative Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Emma P Keane
- Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts
| | - Ming Hwei Yek
- Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Timothy S Sannes
- Department of Psychiatry, UMass Chan Medical School, Worcester, Massachusetts; UMass Memorial Cancer Center, Worcester, Massachusetts
| | - Allison J Applebaum
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Patricia Fank
- Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, Illinois
| | - Pallavi Babu
- Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, Illinois
| | - Cristina Pozo-Kaderman
- Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Hermioni L Amonoo
- Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts; Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts.
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7
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Hamilton BK, Williams P, Galvin J, Turnbull J, Yu J. Disability Associated with Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: Analysis of a Cross-Sectional US Patient Survey. Oncol Ther 2024; 12:451-464. [PMID: 38918341 PMCID: PMC11333386 DOI: 10.1007/s40487-024-00288-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 06/12/2024] [Indexed: 06/27/2024] Open
Abstract
INTRODUCTION Chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT) is associated with poor health-related quality of life (HRQoL) and functional status. However, few studies have evaluated chronic GVHD-related disability and specific activity limitations from a patient perspective. The objective of this analysis was to assess physical, cognitive, and work disability, and describe factors predictive of disability in patients with chronic GVHD in the potentially employable general workforce. METHODS The cross-sectional, online, Living With Chronic GVHD Patient Survey was administered in 2020 to adult US patients who reported an active chronic GVHD diagnosis (i.e., within the previous 5 years) following HSCT. Data included demographics, diagnosis, work status, chronic GVHD symptoms per the Lee Symptom Scale (LSS), and effects on daily living activities. Descriptive and correlational analyses informed composite disability definitions: (1) severe cognitive disability, (2) severe physical disability, and (3) work disability. RESULTS Of 137 respondents with GVHD included in this analysis, 47.0% reported severe cognitive disability, and approximately two-thirds each reported severe physical disability (67.4%) and work disability (62.8%). Chronic GVHD severity/duration, symptoms (Lee Symptom Scale), and number of transplant specialists consulted were associated with all types of disability (univariable analyses). Severe cognitive disability was associated with the number of transplant specialists consulted, severe physical disability with female sex, and work disability with nonwhite race. CONCLUSIONS In this analysis, we found that the presence of specific symptoms and the number of transplant specialists consulted were associated with all types of severe disability; female sex was predictive of severe physical disability and nonwhite race of work disability. These findings add to the understanding of chronic GVHD-associated disability, suggest a need for improved social support for patients, and highlight potential indicators for those most in need.
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Affiliation(s)
- Betty K Hamilton
- Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, USA.
| | | | | | | | - Jingbo Yu
- Incyte Corporation, Wilmington, DE, USA
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8
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El-Jawahri A, Webb JA, Breffni H, Zimmermann C. Integrating Palliative Care and Hematologic Malignancies: Bridging the Gaps for Our Patients and Their Caregivers. Am Soc Clin Oncol Educ Book 2024; 44:e432196. [PMID: 38768404 DOI: 10.1200/edbk_432196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Patients with hematologic malignancies (HMs) struggle with immense physical and psychological symptom burden, which negatively affect their quality of life (QOL) throughout the continuum of illness. These patients are often faced with substantial prognostic uncertainty as they navigate their illness course, which further complicates their medical decision making, especially at the end of life (EOL). Consequently, patients with HM often endure intensive medical care at the EOL, including frequent hospitalization and intensive care unit admissions, and they often die in the hospital. Our EOL health care delivery models are not well suited to meet the unique needs of patients with HMs. Although studies have established the role of specialty palliative care for improving QOL and EOL outcomes in patients with solid tumors, numerous disease-, clinician-, and system-based barriers prevail, limiting the integration of palliative care for patients with HMs. Nonetheless, multiple studies have emerged over the past decade identifying the role of palliative care integration in patients with various HMs, resulting in improvements in patient-reported QOL, symptom burden, and psychological distress, as well as EOL care. Importantly, these studies have also identified active components of specialty palliative care interventions, including strategies to promote adaptive coping especially in the face of prognostic uncertainty. Future work can leverage the knowledge gained from specialty palliative care integration to develop and test primary palliative care interventions by training clinicians caring for patients with HMs to incorporate these strategies into their clinical practice.
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Affiliation(s)
- Areej El-Jawahri
- Massachusetts General Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Jason A Webb
- Knight Cancer Institute, Oregon Health and Sciences University, Portland, Oregon
| | - Hannon Breffni
- Princess Margaret Cancer Centre, Toronto, Ontario, Canada
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9
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Pattipaka T, Sarp S, Nakhaei P, Güneş S. Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program. Bone Marrow Transplant 2024; 59:637-646. [PMID: 38361117 PMCID: PMC11073975 DOI: 10.1038/s41409-024-02207-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 01/03/2024] [Accepted: 01/10/2024] [Indexed: 02/17/2024]
Abstract
The ruxolitinib compassionate use (CU) program offered ruxolitinib to patients ≥2 years of age with confirmed steroid-resistant acute or chronic graft-versus-host disease (aGvHD and cGvHD, respectively). Data from 1180 patients (n = 775, 370 and 35 with cGvHD, aGvHD, and non-specified GvHD, respectively) were analyzed. Most patients had severe cGvHD (56%) or stage III/IV aGvHD (70%) disease and had previously received corticosteroids ( > 80%); ruxolitinib was requested primarily as a second-/third-line option. Patients <12 and ≥12 years old most often received the recommended ruxolitinib doses (5 mg twice daily [BID] and 10 mg BID, respectively); however, 23% and 30% of ≥12 year olds with cGvHD and aGvHD, respectively, received the lower dose of 5 mg BID. Notably, corticosteroid usage decreased with ruxolitinib treatment; at the initial ruxolitinib request, 81% and 91% of patients with cGvHD and aGvHD, respectively, were receiving corticosteroids whereas at resupply, 62% and 64%, respectively, were receiving corticosteroids. Eighty two percent of evaluable patients with cGvHD had a complete or partial response to treatment and 56% of evaluable patients with aGvHD had a best response of grade 0/I. These findings demonstrate the rapid and positive effects of ruxolitinib in patients with GvHD in a real-world setting.
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Affiliation(s)
| | | | - Peyman Nakhaei
- Novartis Pharmaceuticals Canada Inc, Montreal, QC, Canada
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10
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Miyashita E, Sugihara N, Tanaka M, Iwasaki H, Monna-Oiwa M, Isobe M, Kato S, Takahashi S, Nannya Y, Tsuru Y, Konuma T. Prevalence and factors of polypharmacy among disease-free survivors of adults after allogeneic hematopoietic cell transplantation. Leuk Lymphoma 2024; 65:516-520. [PMID: 38149869 DOI: 10.1080/10428194.2023.2298698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/19/2023] [Indexed: 12/28/2023]
Affiliation(s)
- Eita Miyashita
- Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Nozomi Sugihara
- Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Miho Tanaka
- Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hiromi Iwasaki
- Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Maki Monna-Oiwa
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Masamichi Isobe
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Seiko Kato
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satoshi Takahashi
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yasuhito Nannya
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yukari Tsuru
- Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Takaaki Konuma
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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11
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Aldoss I, Clark MC, Wang X, Forman SJ. Leveraging CD19CAR T cells early in the treatment of older patients with B-ALL: are we there yet? Leuk Lymphoma 2024; 65:440-448. [PMID: 38179704 DOI: 10.1080/10428194.2023.2298712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/19/2023] [Indexed: 01/06/2024]
Abstract
Older adults (≥55 years old) with B-cell acute lymphoblastic leukemia (B-ALL) have dismal outcomes with standard chemotherapy as the result of low treatment efficacy and considerable risks for treatment-related morbidity and mortality. There has been a recent success with the introduction of novel therapies, such as blinatumomab and inotuzumab, in the frontline therapeutic paradigm in older adults with B-ALL. However, these agents have their own challenges including the limited durability of remission, the need for additional concurrent chemotherapy and the prolonged course of treatment, and limited efficacy in the setting of extramedullary disease. Here, we hypothesize that the incorporation of chimeric antigen receptor (CAR) T cell therapy as a consolidation treatment in older adults with B-cell ALL in their first complete remission is the ideal setting to advance treatment outcomes by reducing treatment toxicity, enhancing remission durability, and expanding the use of this effective therapy in this age population.
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Affiliation(s)
- Ibrahim Aldoss
- Hematological Malignancies Research Institute, Duarte, CA, USA
- Gehr Family Center for Leukemia Research, Duarte, CA, USA
- Department of Hematology/Hematopoietic Cell Transplantation, Duarte, CA, USA
| | - Mary Caroline Clark
- Hematological Malignancies Research Institute, Duarte, CA, USA
- Department of Clinical and Translational Project Development, Duarte, CA, USA
| | - Xiuli Wang
- Hematological Malignancies Research Institute, Duarte, CA, USA
- T Cell Therapeutic Research Laboratories, City of Hope, Duarte, CA, USA
| | - Stephen Joel Forman
- Hematological Malignancies Research Institute, Duarte, CA, USA
- Department of Hematology/Hematopoietic Cell Transplantation, Duarte, CA, USA
- T Cell Therapeutic Research Laboratories, City of Hope, Duarte, CA, USA
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12
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Konuma T, Yamasaki S, Ishiyama K, Mizuno S, Hayashi H, Uchida N, Shimabukuro M, Tanaka M, Kuriyama T, Onizuka M, Ishiwata K, Sawa M, Tanaka T, Ohigashi H, Fujiwara SI, Matsuoka KI, Ota S, Nishida T, Kanda Y, Fukuda T, Atsuta Y, Nakasone H, Yanada M. Comparison of Allogeneic Transplant Outcomes Between Matched Sibling Donors and Alternative Donors in Patients Over 50 Years of Age with Acute Myeloid Leukemia: 8/8 Allele-Matched Unrelated Donors and Unrelated Cord Blood Provide Better Leukemia-Free Survival Compared with Matched Sibling Donors During Nonremission Status. Transplant Cell Ther 2024; 30:215.e1-215.e18. [PMID: 38081415 DOI: 10.1016/j.jtct.2023.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/11/2023] [Accepted: 12/06/2023] [Indexed: 01/01/2024]
Abstract
Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic cell transplantation (HCT). The increased availability of alternative donor sources has broadened donor types for older patients without HLA-matched sibling donors (MSD). It is uncertain if an MSD should be the first option for allogeneic HCT in patients with AML over 50 years of age. The objective of this study was to compare survival and other post-transplant outcomes between MSDs, 8/8 allele-matched unrelated donors (MUDs), 7/8 allele-MUDs, unrelated cord blood (UCB), and haploidentical donors for patients with AML over 50 years of age. We conducted a retrospective study to compare outcomes in 5704 patients with AML over 50 years of age and receiving allogeneic HCT between 2013 and 2021, using either MSD, 8/8 allele-MUD, 7/8 allele-MUD, UCB, or haploidentical donors in Japan. Complete remission (CR) and nonremission at HCT were analyzed separately for all analyses. In total, 3041 patients were CR, and 2663 patients were nonremission at the time of HCT. In multivariate analysis, donor type did not determine overall survival, irrespective of disease status at HCT. Leukemia-free survival (LFS) was significantly better for 8/8 allele-MUD (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.64 to 0.93; P = .005) and UCB (HR, 0.76; 95% CI, 0.65 to 0.88; P < .001), but not for 7/8 allele-MUD (HR, 0.97; 95% CI, 0.79 to 1.19; P = .794), and haploidentical donor (HR, 0.86; 95% CI, 0.70 to 1.05; P = .146) compared to the MSD group in nonremission status. However, donor type did not determine LFS among CR status. Relapse rates were significantly lower for 8/8 allele-MUD and UCB, whereas nonrelapse mortality was higher for UCB compared to the MSD group among both CR and nonremission status. Our registry-based study demonstrated that MSDs do not lead to superior survival compared to alternative donors for patients with AML over 50 years of age. Furthermore, 8/8 allele-MUDs and UCB provide better LFS compared with MSDs during nonremission status. Therefore, MSD is not necessarily the best donor option for allogeneic HCT in this population.
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Affiliation(s)
- Takaaki Konuma
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
| | - Satoshi Yamasaki
- Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan
| | - Ken Ishiyama
- Department of Hematology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Shohei Mizuno
- Division of Hematology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Japan
| | - Hiromi Hayashi
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naoyuki Uchida
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Masashi Shimabukuro
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Masatsugu Tanaka
- Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan
| | - Takuro Kuriyama
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Makoto Onizuka
- Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan
| | - Kazuya Ishiwata
- Department of Hematology, Toranomon Hospital Kajigaya, Kanagawa, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Takashi Tanaka
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroyuki Ohigashi
- Department of Hematology, Hokkaido University Hospital, Sapporo, Japan
| | | | - Ken-Ichi Matsuoka
- Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
| | - Shuichi Ota
- Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan
| | - Tetsuya Nishida
- Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
| | - Yoshinobu Kanda
- Division of Hematology, Jichi Medical University, Tochigi, Japan
| | - Takahiro Fukuda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Hideki Nakasone
- Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan; Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Masamitsu Yanada
- Department of Hematology and Oncology, Nagoya City University East Medical Center, Nagoya, Japan
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13
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Baumrin E, Loren AW, Falk SJ, Mays JW, Cowen EW. Chronic graft-versus-host disease. Part I: Epidemiology, pathogenesis, and clinical manifestations. J Am Acad Dermatol 2024; 90:1-16. [PMID: 36572065 PMCID: PMC10287844 DOI: 10.1016/j.jaad.2022.12.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/08/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.
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Affiliation(s)
- Emily Baumrin
- Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Alison W Loren
- Blood and Marrow Transplant, Cell Therapy and Transplant Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Sandy J Falk
- Adult Survivorship Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Jacqueline W Mays
- Oral Immunobiology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland
| | - Edward W Cowen
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
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14
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Fatoum H, Zeiser R, Hashmi SK. A personalized, organ-based approach to the treatment of chronic steroid-refractory graft-versus-host disease. Blood Rev 2024; 63:101142. [PMID: 38087715 DOI: 10.1016/j.blre.2023.101142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/07/2023] [Accepted: 11/08/2023] [Indexed: 01/23/2024]
Abstract
Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based on many factors, including wide differences in the organ overall response-rate response and in the current era where multiple agents are approved, and optimal sequencing of drugs based on organ ORR is unknown. We aimed to evaluate outcomes based on ORRs to the most common agents for the treatment of steroid-refractory/steroid-dependent cGvHD by conducting a systematic literature review. A total of 387 studies were evaluated for the ORRs of 12 cGvHD treatments. The highest skin ORR was observed to be 77% though some agents had an acceptable ORR. Most agents had an ocular response ranging from 17 to 50% Some agents resulted in a GI ORR of ≥88%. Rituximab showed the best response for musculoskeletal-GvHD. In the case of lung-GvHD (bronchiolitis obliterans syndrome [BOS]), negligible response was observed in patients treated with various agents. No clinically meaningful responses to treatments were reported for genital-GvHD. Most GvHD trials are focused on the ORR and partial response rates (PRR). The evidence for optimal agents for each organ is limited, and therefore, our study results are striking for differences in organ-ORR yields for a clinically meaningful difference. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD could result in favorable outcomes.
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Affiliation(s)
- Hanaa Fatoum
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Department of Otolaryngology -Head & Neck Surgery, Nottingham University Hospitals NHS Trust, United Kingdom.
| | - Robert Zeiser
- Faculty of Medicine, University of Freiburg, Freiburg, Germany.
| | - Shahrukh K Hashmi
- Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; Department of Medicine, Mayo Clinic, Rochester, MN, USA; College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.
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15
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Konuma T, Itonaga H, Shimomura Y, Fujioka M, Aoki K, Uchida N, Onizuka M, Jinguji A, Tanaka M, Ueda Y, Katayama Y, Sawa M, Tanaka H, Nakamae H, Kawakita T, Maruyama Y, Takahashi S, Ishimaru F, Kanda J, Ichinohe T, Atsuta Y. Single-unit unrelated cord blood transplantation versus HLA-matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry-based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy. Hematol Oncol 2024; 42:e3217. [PMID: 37592904 DOI: 10.1002/hon.3217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 08/19/2023]
Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.
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Affiliation(s)
- Takaaki Konuma
- Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hidehiro Itonaga
- Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Yoshimitsu Shimomura
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Environmental Medicine and Population Science, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Machiko Fujioka
- Department of Hematology, Sasebo City General Hospital, Sasebo, Japan
| | - Kazunari Aoki
- Stem Cell Genetics, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Naoyuki Uchida
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Makoto Onizuka
- Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan
| | - Atsushi Jinguji
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Masatsugu Tanaka
- Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan
| | - Yasunori Ueda
- Department of Hematology/Oncology and Transfusion and Hemapheresis Center, Kurashiki Central Hospital, Kurashiki, Japan
| | - Yuta Katayama
- Department of Hematology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Haruyuki Tanaka
- Department of Hematology, Nara Medical University Hospital, Nara, Japan
| | - Hirohisa Nakamae
- Department of Hematology, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Toshiro Kawakita
- Department of Hematology, National Hospital Organisation Kumamoto Medical Center, Kumamoto, Japan
| | - Yumiko Maruyama
- Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan
| | - Satoshi Takahashi
- Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Fumihiko Ishimaru
- Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan
| | - Junya Kanda
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tatsuo Ichinohe
- Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan
- Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
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16
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Kaundinya T, Kye Y, El-Behaedi SE, Choi JN. Protocol for a feasibility trial (EXPRESS-C-GVHD) for an expressive helping intervention within a support group for cutaneous graft-versus-host-disease. Arch Dermatol Res 2023; 315:2905-2912. [PMID: 37698591 DOI: 10.1007/s00403-023-02718-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 07/20/2023] [Accepted: 08/24/2023] [Indexed: 09/13/2023]
Abstract
BACKGROUND Cutaneous graft-versus-host disease (cuGVHD) is a complication of allogeneic hematopoietic stem cell transplantation that presents with varying severity and can significantly affect one's quality of life (QOL). No trials have yet tested nonpharmacologic interventions to improve the QOL of patients with cuGVHD. The primary objective of the Expressive Helping in Support Groups for Cutaneous GVHD (EXPRESS-C-GVHD) Trial is to evaluate the effect of a support group that employs expressive writing on cutaneous and systemic GVHD symptoms, general distress, and QOL immediately after the intervention. Secondary objectives include evaluating the impact of the intervention on QOL at 1 month post intervention, as well as willingness to participate, compliance, feasibility, and satisfaction. METHODS The EXPRESS-C-GVHD Trial will include patients with chronic cuGVHD who are at least 18 years old and able to use a writing utensil, have access to Zoom, an online video conference platform, and attend all four live support group sessions. Subjects will be recruited from the Department of Dermatology, Northwestern University, Chicago, IL and will participate in a 4 week program via Zoom. Program activities will be 1 h long and consist of 40 min of participant-led verbal reflection and discussion in a group setting in response to prompts, and 20 min of expressive writing. Participants will fill out a baseline willingness survey, follow-up surveys after every session, and post-intervention surveys at 2 weeks and 1 month after intervention. DISCUSSION The EXPRESS-C-GVHD Trial is a pilot trial and will assess whether a Zoom-based expressive writing intervention within the framework of a support group is feasible and can improve QOL outcomes among individuals with cuGVHD. TRIAL REGISTRATION The trial is registered under number NCT05694832.
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Affiliation(s)
- Trisha Kaundinya
- Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Suite 1600, Chicago, IL, 60611, USA
| | - Yae Kye
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Suite 1600, Chicago, IL, 60611, USA
- Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Salma E El-Behaedi
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Suite 1600, Chicago, IL, 60611, USA
- University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
| | - Jennifer N Choi
- Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Suite 1600, Chicago, IL, 60611, USA.
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17
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Perić Z, Basak G, Koenecke C, Moiseev I, Chauhan J, Asaithambi S, Sagkriotis A, Gunes S, Penack O. Understanding the Needs and Lived Experiences of Patients With Graft-Versus-Host Disease: Real-World European Public Social Media Listening Study. JMIR Cancer 2023; 9:e42905. [PMID: 37948101 PMCID: PMC10674148 DOI: 10.2196/42905] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 02/14/2023] [Accepted: 08/04/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Graft-versus-host disease (GVHD) is the major cause of short- and long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Treatment options beyond corticosteroid therapy remain limited, and prolonged treatment often leads to impaired quality of life (QoL). A better understanding of the needs and experiences of patients with GVHD is required to improve patient care. OBJECTIVE The aim of this study is to explore different social media (SM) channels for gathering and analyzing the needs and experiences of patients and other stakeholders across 14 European countries. METHODS We conducted a retrospective analysis of SM data from the public domain. The Talkwalker social analytics tool collected data from open-access forums, blogs, and various social networking sites using predefined search strings. The raw data set derived from the aggregator tool was automatically screened for the relevancy of posts, generating the curated data set that was manually reviewed to identify posts that fell within the predefined inclusion and exclusion criteria. This final data set was then used for the deep-dive analysis. RESULTS A total of 9016 posts relating to GVHD were identified between April 2019 and April 2021. Deduplication and relevancy checks resulted in 325 insightful posts, with Twitter contributing 250 (77%) posts; blogs, 49 (15%) posts; forums, 13 (4%) posts; Facebook, 7 (2%) posts; and Instagram and YouTube, 4 (1%) posts. Patients with GVHD were the primary stakeholders, contributing 63% of all SM posts. In 234 posts, treatment was the most discussed stage of the patient journey (68%), followed by symptoms (33%), and diagnosis and tests (21%). Among treatment-related posts (n=159), steroid therapy was most frequently reported (54/159, 34%). Posts relating to treatment features (n=110) identified efficacy (45/110, 41%), side effects (38/110, 35%), and frequency and dosage (32/110, 29%), as the most frequently discussed features. Symptoms associated with GVHD were described in 24% (77/325) of posts, including skin-related conditions (49/77, 64%), dry eyes or vision change (13/77, 17%), pain and cramps (16/77, 21%), and fatigue or muscle weakness (12/77, 16%). The impacts of GVHD on QoL were discussed in 51% (165/325) of all posts, with the emotional, physical and functional, social, and financial impacts mentioned in 69% (114/165), 50% (82/165), 5% (8/165), and 2% (3/165) of these posts, respectively. Unmet needs were reported by patients or caregivers in 24% (77/325) of analyzed conversations, with treatment-related side effects being the most common (35/77, 45%) among these posts. CONCLUSIONS SM listening is a useful tool to identify medical needs. Treatment of GVHD, including treatment-related side effects, as well as its emotional and physical impact on QoL, are the major topics that GVHD stakeholders mention on SM. We encourage a structured discussion of these topics in interactions between health care providers and patients with GVHD. TRIAL REGISTRATION Not applicable.
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Affiliation(s)
- Zinaida Perić
- School of Medicine, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia
| | - Grzegorz Basak
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | | | - Ivan Moiseev
- RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation
| | | | | | - Alexandros Sagkriotis
- Novartis Pharmaceuticals AG, Basel, Basel, Switzerland
- Gilead Sciences Europe Ltd, Uxbridge, United Kingdom
| | - Sibel Gunes
- Novartis Pharmaceuticals AG, Basel, Basel, Switzerland
| | - Olaf Penack
- Department of Hematology, Oncology, and Tumor Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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18
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Asensi Cantó P, Sanz Caballer J, Solves Alcaína P, de la Rubia Comos J, Gómez Seguí I. Extracorporeal Photopheresis in Graft-versus-Host Disease. Transplant Cell Ther 2023; 29:556-566. [PMID: 37419324 DOI: 10.1016/j.jtct.2023.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 06/29/2023] [Accepted: 07/03/2023] [Indexed: 07/09/2023]
Abstract
Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity following allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP), which exposes mononuclear cells to ultraviolet A irradiation in the presence of a photosensitizing agent, has shown efficacy in the treatment of GVHD. Recent observations in molecular and cell biology have revealed the mechanisms by which ECP can reverse GVHD, including lymphocyte apoptosis, differentiation of dendritic cells from circulating monocytes, and modification of the cytokine profile and T cell subpopulations. Technical innovations have made ECP accessible to a broader range of patients; however, logistical constraints may limit its use. In this review, we scrutinize the development of ECP from its origins to recent insights into the biology underlying ECP efficacy. We also review practical aspects that may complicate successful ECP treatment. Finally, we analyze how these theoretical concepts translate into clinical practice, summarizing the published experiences of leading research groups worldwide.
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Affiliation(s)
- Pedro Asensi Cantó
- Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
| | - Jaime Sanz Caballer
- Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Pilar Solves Alcaína
- Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain; CIBERONC, Instituto Carlos III, Madrid, Spain
| | - Javier de la Rubia Comos
- Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain; School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain
| | - Inés Gómez Seguí
- Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain; CIBERONC, Instituto Carlos III, Madrid, Spain
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19
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Raghunandan S, Gorfinkel L, Graiser M, Bratrude B, Suessmuth Y, Gillespie S, Westbrook AL, Williams KM, Schoettler ML, Kean LS, Horan J, Langston AA, Qayed M, Watkins B. Abatacept for the prevention of GVHD in patients receiving mismatched unrelated transplants: a real-world analysis. Blood Adv 2023; 7:4395-4399. [PMID: 37285800 PMCID: PMC10432595 DOI: 10.1182/bloodadvances.2023010225] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 05/16/2023] [Accepted: 05/31/2023] [Indexed: 06/09/2023] Open
Affiliation(s)
- Sharmila Raghunandan
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA
- Department of Pediatrics, Emory University, Atlanta, GA
| | - Lev Gorfinkel
- Dana-Farber Cancer Institute, Boston Children’s Hospital, Boston, MA
| | | | - Brandi Bratrude
- Dana-Farber Cancer Institute, Boston Children’s Hospital, Boston, MA
| | - Yvonne Suessmuth
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA
- Department of Pediatrics, Emory University, Atlanta, GA
| | | | | | - Kirsten M. Williams
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA
- Department of Pediatrics, Emory University, Atlanta, GA
| | - Michelle L. Schoettler
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA
- Department of Pediatrics, Emory University, Atlanta, GA
| | - Leslie S. Kean
- Dana-Farber Cancer Institute, Boston Children’s Hospital, Boston, MA
| | - John Horan
- Dana-Farber Cancer Institute, Boston Children’s Hospital, Boston, MA
| | | | - Muna Qayed
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA
- Department of Pediatrics, Emory University, Atlanta, GA
| | - Benjamin Watkins
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA
- Department of Pediatrics, Emory University, Atlanta, GA
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20
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Malard F, Holler E, Sandmaier BM, Huang H, Mohty M. Acute graft-versus-host disease. Nat Rev Dis Primers 2023; 9:27. [PMID: 37291149 DOI: 10.1038/s41572-023-00438-1] [Citation(s) in RCA: 96] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/02/2023] [Indexed: 06/10/2023]
Abstract
Acute graft-versus-host disease (GVHD) is a common immune complication that can occur after allogeneic haematopoietic cell transplantation (alloHCT). Acute GVHD is a major health problem in these patients, and is associated with high morbidity and mortality. Acute GVHD is caused by the recognition and the destruction of the recipient tissues and organs by the donor immune effector cells. This condition usually occurs within the first 3 months after alloHCT, but later onset is possible. Targeted organs include the skin, the lower and upper gastrointestinal tract and the liver. Diagnosis is mainly based on clinical examination, and complementary examinations are performed to exclude differential diagnoses. Preventive treatment for acute GVHD is administered to all patients who receive alloHCT, although it is not always effective. Steroids are used for first-line treatment, and the Janus kinase 2 (JAK2) inhibitor ruxolitinib is second-line treatment. No validated treatments are available for acute GVHD that is refractory to steroids and ruxolitinib, and therefore it remains an unmet medical need.
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Affiliation(s)
- Florent Malard
- Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.
| | - Ernst Holler
- University Hospital of Regensburg, Department of Internal Medicine 3, Regensburg, Germany
| | - Brenda M Sandmaier
- Fred Hutchinson Cancer Center, Translational Science and Therapeutics Division, Seattle, WA, USA
- University of Washington School of Medicine, Division of Medical Oncology, Seattle, WA, USA
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China
- Engineering Laboratory for Stem Cell and Immunity Therapy, Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
| | - Mohamad Mohty
- Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.
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21
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Pang Y, Holtzman NG. Immunopathogenic mechanisms and modulatory approaches to graft-versus-host disease prevention in acute myeloid leukaemia. Best Pract Res Clin Haematol 2023; 36:101475. [PMID: 37353287 PMCID: PMC10291443 DOI: 10.1016/j.beha.2023.101475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 05/03/2023] [Accepted: 05/03/2023] [Indexed: 06/25/2023]
Abstract
Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only potential cure for intermediate to high-risk acute myeloid leukaemia (AML). The therapeutic effect of HSCT is largely dependent on the powerful donor-derived immune response against recipient leukaemia cells, known as graft-versus-leukaemia effect (GvL). However, the donor-derived immune system can also cause acute or chronic damage to normal recipient organs and tissues, in a process known as graft-versus-host disease (GvHD). GvHD is a leading cause of non-relapse mortality in HSCT recipients. There are many similarities and cross talk between the immune pathways of GvL and GvHD. Studies have demonstrated that both processes require the presence of mismatched alloantigens between the donor and recipient, and activation of immune responses centered around donor T-cells, which can be further modulated by various recipient or donor factors. Dissecting GvL from GvHD to achieve more effective GvHD prevention and enhanced GvL has been the holy grail of HSCT research. In this review, we focused on the key factors that contribute to the immune responses of GvL and GvHD, the effect on GvL with different GvHD prophylactic strategies, and the potential impact of various AML relapse prevention therapy or treatments on GvHD.
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Affiliation(s)
- Yifan Pang
- Department of Haematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC, USA.
| | - Noa G Holtzman
- Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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22
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Di Francesco G, Cieri F, Esposito R, Sciarra P, Ballarini V, Di Ianni M, Santarone S. Fatigue as Mediator Factor in PTSD-Symptoms after Allogeneic Hematopoietic Stem Cell Transplantation. J Clin Med 2023; 12:jcm12082756. [PMID: 37109093 PMCID: PMC10144210 DOI: 10.3390/jcm12082756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/21/2023] [Accepted: 03/30/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a valid treatment for hematological oncological or metabolic diseases. Despite its therapeutic efficacy, it is an aggressive treatment that impacts negatively on quality of life (QoL) and may result in Post-Traumatic Stress Disorder (PTSD) symptoms. The aim of this study is to explore rates and risk factors for PTSD symptoms, and fatigue in post-HSCT patients with hematological malignancies. METHODS A total of 123 patients after HSCT were evaluated for PTSD symptoms, QoL and fatigue. PTSD symptoms were assessed with the Impact of Event Scale- Revised (IES-R), QoL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) and fatigue symptoms were assessed with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). RESULTS A total of 58.54% of the sample developed PTSD symptoms after transplant. Patients with PTSD symptoms reported significantly lower QoL total scores and significantly higher fatigue than those without PTSD symptoms (p < 0.001). The SEM analysis showed that worse QoL and fatigue affected PTSD symptomatology along different pathways. Fatigue was found as a major influencing factor of PTSD symptoms directly (β = 0.31 **), while QoL only through the mediation of fatigue at a lesser extent. (β = 0.33 *). CONCLUSIONS Our findings indicate that QoL is a concurrent causative factor to the development of PTSD symptomatology through the mediating role of fatigue. Innovative interventions before transplantation to prevent PTSD symptoms should be investigated to improve survival and QoL in patients.
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Affiliation(s)
- Giulia Di Francesco
- Hematology Unit, Department of Oncology-Hematology, Pescara Hospital, 65100 Pescara, Italy
| | - Filippo Cieri
- Department of Neurology, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV 89106, USA
| | - Roberto Esposito
- Clinica Diagnostica Titano (Bianalisi), 47891 Falciano, San Marino
- Azienda Sanitaria Territoriale (AST1), 61121 Pesaro, Italy
| | - Pierpaola Sciarra
- Hematology Unit, Department of Oncology-Hematology, Pescara Hospital, 65100 Pescara, Italy
| | - Valeria Ballarini
- Hematology Unit, Department of Oncology-Hematology, Pescara Hospital, 65100 Pescara, Italy
| | - Mauro Di Ianni
- Hematology Unit, Department of Oncology-Hematology, Pescara Hospital, 65100 Pescara, Italy
| | - Stella Santarone
- Bone Marrow Transplant Unit, Department of Oncology-Hematology, Pescara Hospital, 65100 Pescara, Italy
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23
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Gudmundstuen AM, Efficace F, Tjønnfjord GE, Skaarud KJ, Cottone F, Hjermstad MJ, Iversen PO. The prognostic value of patient-reported outcomes in allogeneic hematopoietic stem cell transplantation: exploratory analysis of a randomized nutrition intervention trial. Ann Hematol 2023; 102:927-935. [PMID: 36864210 PMCID: PMC9998318 DOI: 10.1007/s00277-023-05149-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 02/22/2023] [Indexed: 03/04/2023]
Abstract
Whether patient-reported outcomes (PROs) can predict overall survival (OS) and non-relapse mortality (NRM) among recipients of allogeneic stem cell transplantation (allo-HSCT), is unclear. We performed an exploratory analysis of the prognostic value of patient-reported outcomes (PROs) among 117 recipients of allogeneic stem cell transplantation (allo-HSCT) who participated in a randomized nutrition intervention trial. Cox proportional hazards models were used to investigate possible associations between PROs collected pre-allo-HSCT (baseline) using scores from the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) and 1-year overall survival (OS), whereas logistic regression was used to study associations between these PROs and 1-year non-relapse mortality (NRM). Multivariable analyses indicated that only the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Bone Marrow Transplantation (EBMT) risk score were associated with 1-year OS. In the multivariable model including clinical-sociodemographic factors for 1-year NRM, our analysis showed that living alone (p=0.009), HCT-CI (p=0.016), EBMT risk score (p=0.002), and stem cell source (p=0.046) could be associated with 1-year NRM. Moreover, in the multivariable model, our analysis showed that only appetite loss from the QLQ-C30 was associated with 1-year NRM (p=0.026). In conclusion, in this specific setting, our analysis suggests that the commonly used HCT-CI and EBMT risk scores could be predictive for both 1-year OS and 1-year NRM, whereas baseline PROs in general were not.
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Affiliation(s)
- Anne Marte Gudmundstuen
- Department of Haematology, Oslo University Hospital, 4950 Nydalen, NO-0424, Oslo, Norway. .,Department of Nutrition, Institute of Basic Medical Science, University of Oslo, Oslo, Norway.
| | - Fabio Efficace
- Italian Group for Adult Hematologic Diseases (GIMEMA), Data Centre and Health Outcomes Research Unit, Rome, Italy
| | - Geir Erland Tjønnfjord
- Department of Haematology, Oslo University Hospital, 4950 Nydalen, NO-0424, Oslo, Norway.,K.G. Jebsen Centre for B Cell Malignancies, University of Oslo, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kristin Joan Skaarud
- Department of Haematology, Oslo University Hospital, 4950 Nydalen, NO-0424, Oslo, Norway.,Lovisenberg Diaconal University College, Oslo, Norway
| | - Francesco Cottone
- Italian Group for Adult Hematologic Diseases (GIMEMA), Data Centre and Health Outcomes Research Unit, Rome, Italy
| | - Marianne Jensen Hjermstad
- European Palliative Care Research Centre (PRC) Department of Oncology Oslo University Hospital/Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Regional Advisory Unit for Palliative Care, Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Per Ole Iversen
- Department of Haematology, Oslo University Hospital, 4950 Nydalen, NO-0424, Oslo, Norway.,Department of Nutrition, Institute of Basic Medical Science, University of Oslo, Oslo, Norway
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24
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Patel SS, Hong S, Rybicki L, Farlow S, Dabney J, Kalaycio M, Sobecks R, Majhail NS, Hamilton BK. A Pilot Trial of Patient-Reported Outcomes for Acute Graft-Versus-Host-Disease. Transplant Cell Ther 2023:S2666-6367(23)01205-8. [PMID: 37003415 DOI: 10.1016/j.jtct.2023.03.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/16/2023] [Accepted: 03/23/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Acute GVHD is associated with severe physical and psychosocial symptoms. OBJECTIVES We sought to evaluate the feasibility of capturing patient-reported outcome (PRO) measures in acute GVHD to better measure symptom burden and quality of life (QOL). STUDY DESIGN We conducted a pilot study of adult patients undergoing first allogeneic HCT. Questions from FACT-BMT, PROMIS-10, and PRO-CTCAE were selected, and the survey was administered electronically pre-HCT, at days 14, 50, and 100 post-HCT. In addition, patients who developed grade 2-4 acute GVHD received it weekly for four weeks and then monthly up to 3 months. RESULTS From 2018 to 2020, 73 patients were consented, of which 66 went on to receive HCT and were included in the analysis. Median age at transplant was 63 years, and 92% were Caucasian. Only 47% of expected surveys were completed (range 0-67% for each time point). Descriptive exploratory analysis demonstrate an expected trajectory of QOL using the FACT-BMT and PROMIS-10 scores throughout transplant. Patients who developed acute GVHD (N=15) generally had lower QOL scores compared to those with no or mild GVHD post-HCT. The PRO-CTCAE captured several physical and mental/emotional symptoms in all patients and those with GVHD. Fatigue (100%), decreased appetite (92%), problem tasting (85%), loose stools (77%), pain (77%), skin itching (77%) and depression (feeling sad) (69%) were the most prevalent symptoms among patients with grade 2-4 acute GVHD. Patients with acute GVHD generally reported worse symptoms than those with no/mild GVHD in frequency, severity, and interference in normal activities. Several challenges were identified including poor access/literacy of electronic surveys, acute illness, and need for extensive research/resource support. CONCLUSIONS We demonstrate the challenges yet potential of using PRO measures in acute GVHD. We demonstrate that the PROMIS-10 and PRO-CTCAE measures are able to capture several symptoms and QOL domains of acute GVHD. Further investigation into making PROs feasible in acute GVHD are needed.
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Affiliation(s)
- Sagar S Patel
- Transplant and Cellular Therapy Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
| | - Sanghee Hong
- Blood and Marrow Transplant Program, Duke Cancer Institute, Durham, NC
| | - Lisa Rybicki
- Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Stephanie Farlow
- Blood and Marrow Transplantation, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland OH
| | - Jane Dabney
- Blood and Marrow Transplantation, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland OH
| | - Matt Kalaycio
- Blood and Marrow Transplantation, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland OH
| | - Ronald Sobecks
- Blood and Marrow Transplantation, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland OH
| | | | - Betty K Hamilton
- Blood and Marrow Transplantation, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland OH.
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25
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Yagi H, Shimizu E, Yagi R, Uchino M, Kamoi M, Asai K, Tsubota K, Negishi K, Ogawa Y. Pediatric chronic graft-versus-host disease-related dry eye disease and the diagnostic association of potential clinical findings. Sci Rep 2023; 13:3575. [PMID: 36864106 PMCID: PMC9981701 DOI: 10.1038/s41598-023-30288-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 02/21/2023] [Indexed: 03/04/2023] Open
Abstract
Pediatric graft-versus-host-disease (GVHD)-related dry eye disease (DED) is often overlooked due to a lack of subjective symptoms and reliable testing, leading to irreversible corneal damage. To study the clinical findings contributing to the accurate detection of pediatric GVHD-related DED, a retrospective study of pediatric patients treated with hematopoietic stem cell transplantation (HSCT) at Keio University Hospital between 2004 and 2017 was conducted. Association and diagnostic values of ophthalmological findings for DED were analyzed. Twenty-six patients who had no ocular complications before HSCT were included in the study. Eleven (42.3%) patients developed new-onset DED. The cotton thread test showed excellent diagnostic accuracy in detecting DED (area under the receiver operating curve, 0.96; sensitivity, 0.95; specificity, 0.85) with a cut-off of 17 mm, which was higher than the conventional threshold of 10 mm. Additionally, the presence of filamentary keratitis (FK) and pseudomembranous conjunctivitis (PC) were significantly associated with the diagnosis of DED (p value, 0.003 and 0.001 for FK and PC, respectively) and displayed good diagnostic performance (sensitivity, 0.46 and 0.54; specificity, 0.97 and 0.97 for FK and PC, respectively). In conclusion, the cotton thread test with a new threshold, the presence of PC and FK, could be helpful for promptly detecting pediatric GVHD-related DED.
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Affiliation(s)
- Hitomi Yagi
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Eisuke Shimizu
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Ryuichiro Yagi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Miki Uchino
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Mizuka Kamoi
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Kazuki Asai
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Kazuo Tsubota
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
- Tsubota Laboratory, Inc, Tokyo, Japan
| | - Kazuno Negishi
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Yoko Ogawa
- Department of Ophthalmology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
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26
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Schain F, Boissin C, Laczik T, Fedeli S, Remberger M, Blennow O, Dykes J, Eich T, Jones C, Mattsson J, Berlin G. Real-world clinical characterization, healthcare resource utilization and productivity loss in chronic graft versus host patients exposed to extracorporeal photopheresis in Sweden. Transfus Apher Sci 2023:103705. [DOI: 10.1016/j.transci.2023.103705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 03/09/2023] [Accepted: 03/19/2023] [Indexed: 04/05/2023]
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27
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Salhotra A, Sandhu K, O'Hearn J, Ali H, Nakamura R, Modi BG. A critical review of belumosudil in adult and pediatric patients with chronic graft-versus-host disease. Expert Rev Clin Immunol 2023; 19:241-251. [PMID: 36440483 DOI: 10.1080/1744666x.2023.2152330] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is the main cause of late non-relapse mortality (NRM). Three new agents are now approved to treat cGVHD, of which belumosudil has a unique and dual mechanism of action of i) targeting the Rho-GTPase-associated coiled-coil kinase 2 (ROCK2) in T helper follicular cells (TFH) and TH17 cells, this results in downregulation of proinflammatory cytokines (interleukin -21 and 17), the former in a STAT3-dependent mechanism, ii) inhibition of tissue fibrosis by targeting stress-induced polymerization of G-actin fibrils by inhibiting the Rho-ROCK-MRTF pathway. AREAS COVERED In this review we describe the epidemiology of cGVHD, its cardinal symptoms, preventive and therapeutic options, including second-line approved therapies in the United States (US). Clinical trial data that led to approval of belumosudil is discussed, in addition to the clinical scenarios in which the approved drugs may be most applicable. EXPERT OPINION Belumosudil is approved for treatment of adult and pediatric patients ≥ 12 years with cGVHD after failing two lines of therapy based on results of the ROCKstar study that showed high overall response rates (ORR), favorable adverse effect profiles, and low rates of severe infections. With the availability of three new agents for treatment of cGVHD, treating physicians have more therapeutic options for patients and have additional options of development new clinical trials using a combination of recently approved drugs.
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Affiliation(s)
- Amandeep Salhotra
- Department of Hematology and HCT, City of Hope National Medical Center, Duarte, CA, USA
| | - Karamjeet Sandhu
- Department of Hematology and HCT, City of Hope National Medical Center, Duarte, CA, USA
| | - James O'Hearn
- Department of Hematology and HCT, City of Hope National Medical Center, Duarte, CA, USA
| | - Haris Ali
- Department of Hematology and HCT, City of Hope National Medical Center, Duarte, CA, USA
| | - Ryotaro Nakamura
- Department of Hematology and HCT, City of Hope National Medical Center, Duarte, CA, USA
| | - Badri G Modi
- Department of Surgery, Division of Dermatology, City of Hope National Medical Center, Duarte, CA, USA
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28
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Zhang X, Wang J, Liu Y, Liu J, Wang B, Zhang Q, Guan W, Zhang H, Xu L, Liu G, Zhang P, He Y, Feng S, Han M, Li C, Jiang E, Xie W. Long-term survivors demonstrate superior quality of life after haploidentical stem cell transplantation to matched sibling donor transplantation. J Transl Med 2022; 20:596. [PMID: 36517908 PMCID: PMC9749359 DOI: 10.1186/s12967-022-03803-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/01/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND It has been well-documented that haplo-identical hematopoietic stem cell transplantation (HID-HSCT) can provide outcomes comparable to conventional matched sibling donor (MSD) HSCT, however, little is known about the effects on quality of life (QoL) in long-term survivors. This study is to investigate the differences in longitudinal performance of QoL between HID and MSD HSCT using a comprehensive assessment system. METHODS This prospective study enrolled consecutive patients who had received allogenic-HSCT (allo-HSCT) between January 2018 and December 2019 in our center. All patients were informed to complete QoL questionnaires including the Mos 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, version 4), using an online applet, before transplantation and at scheduled time points after transplantation. The linear mixed-effects model was used to analyze the variation trend of different dimensions of both SF-36 and FACT-BMT with different follow-up times. RESULTS Of the 425 participants, recipients of HID and MSD who survived more than 1 year (n = 230) were included in the final analysis of QoL (median age [range]: 36, [15, 66]). The 3 year overall survival (OS) of HID and MSD was 82.42% and 86.46%, respectively. QoL was assessed using both SF-36 and FACT-BMT and there was longitudinal recovery with clinical significance in the cohort. Compared to MSD-HSCT patients, HID-HSCT recipients demonstrated superior QoL performance in some subscales describing physical and mental wellness. Specifically, the difference in physical performance is more remarkable using FACT-BMT whereas that in mental wellness is more significant using SF36. In the subsequent stratified analysis, patients with a history of aGVHD or CMV reactivation demonstrated inferior QoL. CONCLUSIONS Long-term survivors of HID HSCT achieved better QoL in some sub-scales compared to MSD HSCT. In addition, SF-36 and FACT-BMT demonstrated different performance thus combination of both improved capacity of the evaluation system.
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Affiliation(s)
- Xiaoyu Zhang
- Department of Hematopoietic Stem Cell Transplantation, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China
| | - Jiao Wang
- Department of Public Health, Tianjin Medical University, 288 Nanjing Road, Tianjin, 300052, China
| | - Yuqiu Liu
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Jie Liu
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Bei Wang
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Qiuhui Zhang
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Wei Guan
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Huijuan Zhang
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Li Xu
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Guiying Liu
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China
| | - Ping Zhang
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA
| | - Yi He
- Department of Hematopoietic Stem Cell Transplantation, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China
| | - Sizhou Feng
- Department of Hematopoietic Stem Cell Transplantation, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China
| | - Mingzhe Han
- Department of Hematopoietic Stem Cell Transplantation, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China
| | - Changping Li
- Department of Public Health, Tianjin Medical University, 288 Nanjing Road, Tianjin, 300052, China
| | - Erlie Jiang
- Department of Hematopoietic Stem Cell Transplantation, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.
| | - Wenjun Xie
- Department of Nursing Care, State Key Laboratory of Experimental Hematology, Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, National Clinical , Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Roa, Tianjin, 300020, China.
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Yu J, Hamilton BK, Turnbull J, Stewart SK, Vernaya A, Bhatt V, Meyers O, Galvin J. Patient-reported symptom burden and impact on daily activities in chronic graft-versus-host disease. Cancer Med 2022; 12:3623-3633. [PMID: 36394207 PMCID: PMC9939096 DOI: 10.1002/cam4.5209] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/23/2022] [Accepted: 08/23/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Chronic graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) treatment for hematologic malignancies. There are limited patient-reported data concerning symptom burden and effects on activities of daily living (ADL). METHODS The cross-sectional Living With Chronic GVHD Patient Survey was administered online in the United States (May-August 2020) to participants aged ≥18 years who underwent allogeneic HSCT, were diagnosed with chronic GVHD by a healthcare provider, and self-reported active chronic GVHD (within past 5 years). Information on patient demographics, disease characteristics, symptom burden, and ability to perform ADL was collected. Symptom burden was assessed using the validated Lee Symptom Scale (range from 0-100 with higher scores indicating greater burden). All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. RESULTS Out of 580 participants who entered the survey screener, 165 participants (28.4%) across 33 states fulfilled all study eligibility criteria, completed the entire survey, and were included (age: mean [SD], 53.7 (13.8) years; median [range], 57.0 [18-78] years; female, n = 105 [63.6%]; White, n = 137 [83.0%]). Respondents described their chronic GVHD severity primarily as moderate (n = 54 [32.7%]) or severe (n = 102 [61.8%]) at the time when symptoms were at their worst. One-third of respondents (33.9%) indicated that their chronic GVHD symptoms were at their worst for ≥1 year in duration. Mean (SD; range) Lee Symptom Scale score was 44.8 (19.4; 2-100); 44% of respondents considered "dry eye" the most burdensome symptom. Almost half of respondents (n = 73 [44.2%]) rated their overall quality of life (QoL) as poor. Participants reported a detrimental impact of symptoms on ADL, including basic activities (eg, eating, personal hygiene, dressing). CONCLUSIONS Survey respondents self-reported high chronic GVHD symptom burden and felt that their symptoms severely interfered with physical function and ADL. Effective strategies to mitigate chronic GVHD symptoms are needed to improve QoL among HSCT survivors.
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Affiliation(s)
- Jingbo Yu
- Incyte CorporationWilmingtonDelawareUSA
| | | | | | - Susan K. Stewart
- Blood & Marrow Transplant Information NetworkHighland ParkIllinoisUSA
| | - Alla Vernaya
- Patient Centered Endpoints, IQVIANew YorkNew YorkUSA
| | | | - Oren Meyers
- Patient Centered Endpoints, IQVIANew YorkNew YorkUSA
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Kaundinya T, El-Behaedi S, Choi JN. Content analysis and dermatologic gaps in online patient education materials for graft-versus-host disease. Arch Dermatol Res 2022; 315:1063-1066. [PMID: 36335547 DOI: 10.1007/s00403-022-02452-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/20/2022] [Accepted: 10/26/2022] [Indexed: 11/08/2022]
Abstract
Graft-versus-host disease (GVHD) is a complex systemic disease which is associated with significant physical and psychological distress in patients. Given the complexity of this disorder and its multifactorial effects, it is important for patients to have access to education and learning about their disease. Patient education has been shown to reduce the uncertainty and stress that follows complex diseases such as GVHD. To our knowledge no studies have evaluated the content of patient education materials on GVHD, especially from a dermatologic perspective. Despite the complexity of GVHD, cutaneous manifestations are common and often require management by dermatology. In this cross-sectional study, a Google search engine was utilized to assess websites for information on GVHD etiology, pathophysiology, symptoms, treatment, coverage of Acute GVHD, Chronic GVHD, cutaneous presentations, dermatologic management, and quality of life. It was evident that there was inconsistent inclusion of cutaneous manifestations of acute and chronic GVHD and dermatologic management of GVHD. Results of this study emphasize the need for more robust integration of skin-specific information guided by expert dermatologist opinion in publicly available patient education materials online.
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31
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Asensi Cantó P, Sanz Caballer J, Fuentes Socorro C, Solves Alcaína P, Lloret Madrid P, Solís Ruíz J, Torres Guerola B, de la Rubia Comos J, Fernández Navarro JM, Gómez-Seguí I. Role of extracorporeal photopheresis in the management of children with graft-vs-host disease. J Clin Apher 2022; 37:573-583. [PMID: 36134700 DOI: 10.1002/jca.22012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 07/24/2022] [Accepted: 08/19/2022] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Graft-vs-host disease (GVHD) is a frequent cause of morbidity and mortality in allogeneic stem cell transplants. Extracorporeal photopheresis (ECP) is one of the most accepted second-line treatments, but technical issues of ECP in children might be prohibitive. MATERIALS AND METHODS Patients under 18 y of age with corticodependant or corticorefractory GVHD receiving ECP at our hospital were included in this retrospective study. ECP was performed with an in-line system (CellExTherakos) in 2013-2014 and with an off-line system (Spectra Optia) from 2015 onwards. Cumulative incidence curves were obtained to compare ECP efficacy among patients grouped by different baseline, apheresis, and disease characteristics. Significant variables on univariate analysis (Gray's test) were pooled into a multivariate analysis (Fine-Gray proportional hazard regression for competing events). RESULTS A total of 701 ECP sessions were performed on 33 patients between October 2013 and December 2021. In total, 97% of the sessions could be executed. In 8% of the sessions an incident was detected, most of them mild and related to catheter dysfunction. With a median follow-up for alive patients of 33.6 mo (range, 8-95), the composite partial and complete response cumulative incidence was 70% (95% confidence interval, 51%-82%) and the median time to maximal response was 2.8 mo (range, 0.25-9.8). Significantly lower response ratios were found in patients with hepatic, gastrointestinal, acute, or severe GVHD. The only variable that influenced response on multivariate analysis was GVHD severity. DISCUSSION ECP is feasible, safe, and effective for pediatric patients with corticorefractory or corticodependant GVHD, offering a less toxic and nonimmunosuppressive treatment option.
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Affiliation(s)
- Pedro Asensi Cantó
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Jaime Sanz Caballer
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | | | - Pilar Solves Alcaína
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,CIBERONC, Instituto Carlos III, Madrid, Spain
| | - Pilar Lloret Madrid
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Jürgen Solís Ruíz
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | | | - Javier de la Rubia Comos
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,CIBERONC, Instituto Carlos III, Madrid, Spain.,School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain
| | | | - Ines Gómez-Seguí
- Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,CIBERONC, Instituto Carlos III, Madrid, Spain
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32
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Nagler A. Haploidentical hematopoietic stem cell transplantation in severe aplastic anemia: time for long term and quality of life assessed studies. Sci Bull (Beijing) 2022; 67:1743-1744. [PMID: 36546059 DOI: 10.1016/j.scib.2022.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Arnon Nagler
- The Division of Hematology, Bone Marrow Transplantation and the Hematooncology Center, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel; Tel-Aviv University and Sackler School of Medicine, Tel-Aviv 52621, Israel.
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33
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Schroeder MA, Hari PN, Blithe A, Paranagama D, Bhatt V, DiPersio JF. Safety analysis of patients who received ruxolitinib for steroid-refractory acute or chronic graft-versus-host disease in an expanded access program. Bone Marrow Transplant 2022; 57:975-981. [PMID: 35437311 DOI: 10.1038/s41409-022-01673-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 03/18/2022] [Accepted: 04/01/2022] [Indexed: 11/08/2022]
Abstract
Outside of clinical trials and before commercial availability for acute and chronic graft-versus-host disease (GVHD), the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was available to US patients with steroid-refractory GVHD through an open-label, multicenter expanded access program (EAP) sponsored by Incyte Corporation. To assess the safety of ruxolitinib, data on serious adverse events (SAEs) reported among patients in the EAP were collected. Patients ≥12 years old who received allogeneic hematopoietic cell transplantation for a hematologic malignancy and developed any-grade acute or chronic steroid-refractory GVHD received ruxolitinib at a starting dose of 5 mg twice daily (BID; acute GVHD) or 10 mg BID (chronic GVHD). At data extraction (May 8, 2020), 60 patients with acute GVHD and 549 with chronic GVHD were enrolled. In the acute and chronic GVHD cohorts, 41 (68.3%) and 186 (33.9%) patients, respectively, had ≥1 SAE. Sepsis (8.3%) and respiratory failure (6.7%) were the most common SAEs in the acute GVHD cohort, and pneumonia (4.9%), sepsis (3.8%), and lung infection (3.5%) in chronic GVHD. Infection SAEs were reported in 23.3% and 20.0% of patients with acute and chronic GVHD, respectively. Overall, these safety findings demonstrate the tolerability of ruxolitinib in steroid-refractory GVHD.
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Affiliation(s)
- Mark A Schroeder
- Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
| | - Parameswaran N Hari
- Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Amy Blithe
- US Medical Affairs, Incyte Corporation, Wilmington, DE, USA
| | | | - Valkal Bhatt
- US Medical Affairs, Incyte Corporation, Wilmington, DE, USA
| | - John F DiPersio
- Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
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Kwan ACF, Blosser N, Ghosh S, Leyshon C, Dersch-Mills D, Puckrin RP, Duggan P, Zepeda V, Savoie L, Stewart D, Storek J, Jamani K. Toward optimization of cyclosporine concentration target to prevent acute graft-vs-host disease following myeloablative allogeneic stem cell transplant. Clin Transplant 2022; 36:e14732. [PMID: 35606904 DOI: 10.1111/ctr.14732] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/09/2022] [Accepted: 05/14/2022] [Indexed: 11/28/2022]
Abstract
Despite the common use of cyclosporine (CsA) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic stem cell transplant, the optimal CsA trough target remains unknown. Here, we report on outcomes of adult patients following myeloablative conditioning to identify an optimal CsA trough target and characterize the most relevant timeframe post-transplant for CsA trough targeting to minimize aGVHD. We retrospectively reviewed 399 consecutive patients who underwent first peripheral blood allogeneic stem cell transplant for hematological malignancies between January 2009 and December 2018. In the unadjusted and adjusted analyses, the incidence of grades 2-4 aGVHD was significantly higher among patients with an average CsA trough concentration <250 mcg/L compared to patients with an average CsA trough concentration ≥250 mcg/L during days 15-28 post-transplant (31.5% versus 18.8%, P = 0.037), with an odds ratio (OR) of 1.97 (95% confidence interval 1.04-3.71). In contrast, no correlations between CsA trough concentration and relapse, non-relapse mortality and overall survival was found. In conclusion, early post-transplant CsA trough concentrations are an important factor in the prophylaxis against aGVHD. Our findings suggest that CsA trough concentrations should be maximized between days 15-28 post-myeloablative transplant. This article is protected by copyright. All rights reserved.
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Affiliation(s)
| | - Nikki Blosser
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
| | - Sunita Ghosh
- Cross Cancer Institute, Edmonton, Alberta, Canada
| | | | | | | | - Peter Duggan
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
| | - Victor Zepeda
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
| | - Lynn Savoie
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
| | - Douglas Stewart
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
| | - Jan Storek
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
| | - Kareem Jamani
- Alberta Blood & Marrow Transplant Program, Calgary, Alberta, Canada
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Bujan Rivera J, Kühl R, Zech U, Hendricks A, Luft T, Dreger P, Friedmann-Bette B, Betz TM, Wiskemann J. Impact of Resistance Exercise and Nutritional Endorsement on physical performance in patients with GvHD (IRENE-G study) - design and rational of a randomized controlled trial. BMC Cancer 2022; 22:440. [PMID: 35459108 PMCID: PMC9024288 DOI: 10.1186/s12885-022-09497-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/06/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Graft-versus-host disease (GvHD) remains a major complication and limitation to successful allogeneic hematopoietic stem cell transplantation. Treatment of GvHD is challenging due to its heterogeneous nature of presentation, with steroids remaining the established first-line treatment. Long-term doses of systemic corticosteroids have many well-known side-effects including muscle atrophy. Despite the fact that reports in non-cancer clinical populations treated with glucocorticoids demonstrated that resistance training can reverse atrophy and weakness, no RCT has evaluated the potential of resistance training on preventing the disease- and treatment-induced loss of skeletal muscle mass and function in GvHD patients yet. In this context, ensuring adequate nutrition is important as protein deprivation may accelerate the wasting process. As GvHD patients are commonly found to be malnourished, nutritional medical care should be considered when investigating the effect of exercise in GvHD patients. Therefore, the aim of the present "Impact of Resistance Exercise and Nutritional Endorsement on physical performance in patients with GvHD" - Study (IRENE-G) is to evaluate the effects of resistance exercise in combination with nutritional endorsement on physical, nutritional and patient-reported outcomes in GvHD patients. METHODS IRENE-G is a 24-week prospective interventional RCT. One hundred twelve participants will be randomly allocated (1:1) to one of two arms: resistance exercise and nutritional optimization (experimental) vs. nutritional optimization only (control). Participants in the experimental group will engage in a supervised, progressive moderate-to-high intensity resistance training that is consistent with exercise guidelines for cancer patients, while additionally receiving nutritional support/therapy. Subjects of the control group solely receive nutritional support/therapy based on individual needs. Participants will be assessed at baseline, at 8, 16, 24 weeks for physical performance and various physiological, nutritional and patient-reported outcomes. Follow-up will be 6 months after intervention completion. DISCUSSION To our knowledge, this will be the first RCT to assess and compare the effects of a resistance intervention supplemented by nutritional support/therapy against nutritional support only on various health-related outcomes in GvHD patients. The study will contribute to our understanding of the value of exercise and nutritional endorsement in counteracting the negative consequences of GvHD and its treatment. TRIAL REGISTRATION ClinicalTrials.gov : NCT05111834 . Registered 8 November 2021 - Retrospectively registered.
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Affiliation(s)
- Janina Bujan Rivera
- Division of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany
| | - Rea Kühl
- Division of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany
| | - Ulrike Zech
- Department of Internal Medicine I, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Anne Hendricks
- Department of Internal Medicine I, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Thomas Luft
- Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Peter Dreger
- Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Birgit Friedmann-Bette
- Department of Internal Medicine VII, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Theresa-Maria Betz
- Department of Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Joachim Wiskemann
- Division of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
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36
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Posttransplant Cyclophosphamide for Prevention of Graft-versus-Host Disease: The Prospective Randomized HOVON-96 Trial. Blood Adv 2022; 6:3378-3385. [PMID: 35143644 PMCID: PMC9198908 DOI: 10.1182/bloodadvances.2021005847] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 01/10/2022] [Indexed: 12/02/2022] Open
Abstract
PT-Cy after NMA matched alloHSCT will increase the proportion of patients that survive without severe GVHD. PT-Cy could allow for implementation of early posttransplant chemo- and immunotherapy to further reduce the relapse risk after alloHSCT. Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse-free survival (GRFS) as compared with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA-matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA; a total of 151 patients were transplanted (52 vs 99 patients, respectively). The cumulative incidence of grade 2 to 4 acute GVHD at 6 months was 48% in recipients of CsA/MPA vs 30% following PT-Cy/CsA (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.82; P = .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16% (HR, 0.36; 95% CI, 0.21-0.64; P < .001). The 1-year estimate of GRFS was 21% (11% to 32%) vs 45% (35% to 55%), P < .001. With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD.
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37
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Williams KM, Pavletic SZ, Lee SJ, Martin PJ, Farthing DE, Hakim FT, Rose J, Manning-Geist BL, Gea-Banacloche JC, Comis LE, Cowen EW, Justus DG, Baird K, Cheng GS, Avila D, Steinberg SM, Mitchell SA, Gress RE. Prospective phase II trial of montelukast to treat bronchiolitis obliterans syndrome after hematopoietic cell transplant and investigation into BOS pathogenesis. Transplant Cell Ther 2022; 28:264.e1-264.e9. [PMID: 35114411 PMCID: PMC9081205 DOI: 10.1016/j.jtct.2022.01.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/16/2022] [Accepted: 01/24/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of chronic graft-versus-host disease (cGVHD) following hematopoietic cell transplantation (HCT). Montelukast interrupts cysteinyl leukotriene activity and may diminish the activation and homing of cells to bronchioles and subsequent fibrosis. OBJECTIVE We performed a prospective phase II trial to test whether montelukast altered lung decline for patients with BOS after HCT. STUDY DESIGN We performed a single arm, open-label, multi-institutional study with primary endpoints of: i) FEV1 stability or improvement (<15% decline) and ii) slope of FEV1<1 point decline after six months treatment. Secondary endpoints included symptom and functional response, and immune correlates investigating the role of leukotrienes in BOS progression. RESULTS 25 patients enrolled with moderate to severe lung disease after three months of stable cGVHD therapy. Montelukast was well-tolerated and no patient required escalation of BOS-directed therapy. At the primary endpoint, all evaluable patients (n=23) met criteria for treatment success using FEV1% predicted, and all but one had stable or improved FEV1 slope. In those with >5% FEV1 improvement, clinically meaningful improvements were seen in the Lee scores of breathing, energy, and mood. Improvements in the Human Activity Profile and 6-minute-walk test were observed in those with <5% FEV1 decline. Overall survival was 87% at two-years. Immune correlates showed elevated leukotriene receptor levels on blood eosinophils and monocytes vs. healthy controls, elevated urine leukotrienes in 45% of cohort, and cysteinyl leukotriene receptors on bronchoalveolar lavage subsets and a predominance of Th2 T cells, all pre-treatment. CONCLUSIONS These data suggest that montelukast may safely halt progression of BOS after HCT and that leukotrienes may play a role in the biology of BOS.
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Affiliation(s)
- Kirsten M Williams
- Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, 1760 Haygood Drive, 3rd floor W362, Atlanta GA, US, 30322.
| | - Steven Z Pavletic
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda MD, US, 20892
| | - Stephanie J Lee
- Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA, US 98109
| | - Paul J Martin
- Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA, US 98109
| | - Don E Farthing
- Experimental Transplantation and Immunotherapy Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, US, 20892
| | - Frances T Hakim
- Experimental Transplantation and Immunotherapy Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, US, 20892
| | - Jeremy Rose
- Experimental Transplantation and Immunotherapy Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, US, 20892
| | - Beryl L Manning-Geist
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, US, 10065
| | - Juan C Gea-Banacloche
- Division of Clinical Research, National Institute of Allergy and Immunology, National Institutes of Health, 10 Center Drive, Bethesda, MD, US, 20892
| | - Leora E Comis
- Rehabilitation Medicine Department, Clinical Center, NIH, Bethesda, MD
| | - Edward W Cowen
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 10 Center Dr, Room 12N240A, Bethesda, MD, US, 20892
| | - David G Justus
- Department of Laboratory Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, US
| | - Kristin Baird
- Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD
| | - Guang-Shing Cheng
- Department of Medicine, University of Washington, Seattle, WA, US, 98109; Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA, US 98109
| | - Daniele Avila
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda MD, US, 20892
| | - Seth M Steinberg
- Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, US, 20892
| | - Sandra A Mitchell
- Outcomes Research Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda MD, US, 20892
| | - Ronald E Gress
- Experimental Transplantation and Immunotherapy Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, US, 20892
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Hong S, L R, Mclellan L, Dabney J, Gerds TA, Rotz S, Kalaycio M, Hanna R, Hamilton BK, Majhail N, Sobecks RM. Comparison of Quality of Life and Outcomes between Haploidentical and Matched Related/Unrelated Donor Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther 2022; 28:217.e1-217.e6. [DOI: 10.1016/j.jtct.2022.01.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/04/2022] [Accepted: 01/12/2022] [Indexed: 11/17/2022]
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Martini DJ, Chen YB, DeFilipp Z. OUP accepted manuscript. Oncologist 2022; 27:685-693. [PMID: 35443042 PMCID: PMC9355804 DOI: 10.1093/oncolo/oyac076] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/17/2022] [Indexed: 11/29/2022] Open
Abstract
Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality. For many years, there have been few effective treatment options for patients with GVHD. First-line systemic treatment remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor. Elucidation of the pathophysiological mechanisms of acute and chronic GVHD has laid a foundation for novel therapeutic approaches. Since 2017, there have now been 4 approvals by the US Food and Drug Administration (FDA) for GVHD. Ruxolitinib, an oral selective JAK1/2 inhibitor, received FDA approval for the treatment of steroid-refractory acute GVHD in 2019 and remains the only agent approved for acute GVHD. There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. In this review, we highlight the clinical data which support these FDA approvals in acute and chronic GVHD with a focus on mechanism of actions, clinical efficacy, and toxicities associated with these agents.
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Affiliation(s)
- Dylan J Martini
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Yi-Bin Chen
- Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA, USA
| | - Zachariah DeFilipp
- Corresponding author: Zachariah DeFilipp, MD, 55 Fruit Street, Zero Emerson Place, Suite 118, Office 134, Boston, USA. Tel: +1 617-726-5765; Fax: +1 617-643-5843;
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Saraceni F, Scortechini I, Fiorentini A, Dubbini MV, Mancini G, Federici I, Colaneri FR, Lotito AF, Guerzoni S, Puglisi B, Olivieri A. Conditioning Regimens for Frail Patients with Acute Leukemia Undergoing Allogeneic Stem Cell Transplant: How to Strike Gently. Clin Hematol Int 2021; 3:153-160. [PMID: 34938987 PMCID: PMC8690700 DOI: 10.2991/chi.k.210731.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 07/25/2021] [Indexed: 01/06/2023] Open
Abstract
Despite the recent dramatic progress in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) therapy, allogeneic transplant remains a mainstay of treatment for patients with acute leukemia. The availability of novel compounds and low intensity chemotherapy regimens made it possible for a significant proportion of elderly and comorbid patients with AML or ALL to undergo curative treatment protocols. In addition, the expansion of donor availability and the recent dramatic progress in haploidentical stem cell transplant, allow the identification of an available donor for nearly every patient. Therefore, an increasing number of transplants are currently performed in elderly and frail patients with AML or ALL. However, allo-Hematopoietic stem cell transplant (HSCT) in this delicate setting represents an important challenge, especially regarding the selection of the conditioning protocol. Ideally, conditioning intensity should be reduced as much as possible; however, in patients with acute leukemia relapse remains the major cause of transplant failure. In this article we present modern tools to assess the patient health status before transplant, review the available data on the outcome of frail AML an ALL patients undergoing allo-HSCT, and discuss how preparatory regimens can be optimized in this setting.
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Affiliation(s)
- Francesco Saraceni
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Ilaria Scortechini
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Alessandro Fiorentini
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Maria Vittoria Dubbini
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Giorgia Mancini
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Irene Federici
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | | | | | - Selene Guerzoni
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Bruna Puglisi
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
| | - Attilio Olivieri
- Hematology and Stem Cell Transplant, Ospedali Riuniti Ancona, Via Conca 71, Ancona, Italy
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El-Jawahri A. What else do I need to worry about when treating graft-versus-host disease? HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2021; 2021:655-661. [PMID: 34889363 PMCID: PMC8791094 DOI: 10.1182/hematology.2021000302] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Graft-versus-host disease (GVHD) is the main cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant survivors. Patients with acute and chronic GVHD often endure substantial symptom burden and quality of life (QOL) and functional impairments. Living with GVHD affects multiple domains of patient-reported QOL, physical functioning, and psychological well-being. Patients describe living with GVHD as a life-altering "full-time job" requiring unique knowledge, personal growth, and resilient coping strategies. Managing the supportive care needs of patients living with GVHD must include (1) monitoring of patient-reported QOL and symptom burden; (2) routine screening for psychological distress and implementing therapeutic strategies to treat depression, anxiety, and posttraumatic stress symptoms; (3) a systematic review of care needs by a multidisciplinary team experienced in managing transplant-related complications and organ-specific GVHD symptoms; and (4) ensuring optimal prevention and management of infection complications in this highly immunocompromised population. Improving the QOL in patients with GVHD requires a multidisciplinary approach with emphasis on aggressive symptom management, psychological coping, and promoting physical activity and rehabilitation in this population living with immense prognostic uncertainty and struggling to adapt to this difficult and unpredictable illness.
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Affiliation(s)
- Areej El-Jawahri
- Correspondence Areej El-Jawahri, Hematology-Oncology, Massachusetts General Hospital, 55 Fruit St, Yawkey 9E, Boston, MA 02114; e-mail:
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Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease. Clin Drug Investig 2021; 41:929-939. [PMID: 34657244 PMCID: PMC8556206 DOI: 10.1007/s40261-021-01087-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2021] [Indexed: 11/25/2022]
Abstract
Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is graft-versus-host disease (GvHD). Acute GvHD (aGvHD) generally causes skin, gastrointestinal and liver symptoms, but chronic GvHD (cGvHD) has a different pathophysiology and may affect nearly every organ or tissue of the body. In Europe, GvHD prophylaxis is generally a calcineurin inhibitor in combination with methotrexate, with high-dose systemic steroids used for advanced GvHD treatment. Between 39% and 59% of alloHSCT patients will develop aGvHD and around 36–37% will develop cGvHD. Steroid response decreases with increasing disease severity, which in turn leads to an increase in non-relapse mortality. GvHD imposes a financial burden on healthcare systems, significantly increasing post-alloHSCT costs. Increased GvHD disease severity magnifies this. Balancing immunosuppression to control the GvHD whilst maintaining a degree of immunocompetence against infection is critical. European GvHD guidelines acknowledge the lack of evidence to support a standard second-line therapy, and improved long-term outcomes and quality-of-life (QoL) remain an unmet need. Evidence generation for potential treatments is challenging. Issues to overcome include choice of comparator (extensive off-label usage); blinding; selection of relevant patient-reported outcome measures (PROMs); and rarity of the condition, which may infeasibly increase timescales to achieve clinical and statistical relevance.
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Zewde MG, Morales G, Gandhi I, Özbek U, Aguayo-Hiraldo P, Ayuk F, Baez J, Chanswangphuwana C, Choe H, DeFilipp Z, Etra A, Grupp S, Hexner EO, Hogan W, Javorniczky NR, Kasikis S, Kitko CL, Kowalyk S, Meedt E, Merli P, Nakamura R, Qayed M, Reshef R, Rösler W, Schechter T, Weber D, Wölfl M, Yanik G, Young R, Levine JE, Ferrara JLM, Chen YB. Evaluation of Elafin as a Prognostic Biomarker in Acute Graft-versus-Host Disease. Transplant Cell Ther 2021; 27:988.e1-988.e7. [PMID: 34474163 DOI: 10.1016/j.jtct.2021.08.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 11/17/2022]
Abstract
Acute graft-versus-host disease (GVHD) is a major cause of mortality in patients undergoing hematopoietic cell transplantation (HCT) for hematologic malignancies. The skin is the most commonly involved organ in GVHD. Elafin, a protease inhibitor overexpressed in inflamed epidermis, was previously identified as a diagnostic biomarker of skin GVHD; however, this finding was restricted to a subset of patients with isolated skin GVHD. The main driver of nonrelapse mortality (NRM) in HCT recipients is gastrointestinal (GI) GVHD. Two biomarkers, Regenerating islet-derived 3a (REG3α) and Suppressor of tumorigenesis 2 (ST2), have been validated as biomarkers of GI GVHD that predict long-term outcomes in patients treated for GVHD. We undertook this study to determine the utility of elafin as a prognostic biomarker in the general population of acute GVHD patients in whom GVHD may develop in multiple organs. We analyzed serum elafin concentrations as a predictive biomarker of acute GVHD outcomes and compared it with ST2 and REG3α in a large group of patients treated at multiple centers. A total of 526 patients from the Mount Sinai Acute GVHD International Consortium (MAGIC) who had received corticosteroid treatment for skin GVHD and who had not been previously studied were analyzed. Serum concentrations of elafin, ST2, and REG3α were measured by ELISA in all patients. The patients were divided at random into equal training and validation sets, and a competing-risk regression model was developed to model 6-month NRM using elafin concentration in the training set. Additional models were developed using concentrations of ST2 and REG3α or the combination of all 3 biomarkers as predictors. Receiver operating characteristic (ROC) curves were constructed using the validation set to evaluate the predictive accuracy of each model and to stratify patients into high- and low-risk biomarker groups. The cumulative incidence of 6-month NRM, overall survival (OS), and 4-week treatment response were compared between the risk groups. Unexpectedly, patients in the low-risk elafin group demonstrated a higher incidence of 6-month NRM, although the difference was not statistically significant (17% versus 11%; P = .19). OS at 6 months (68% versus 68%; P > .99) and 4-week response (78% versus 78%; P = .98) were similar in the low-risk and high-risk elafin groups. The area under the ROC curve (AUC) was 0.55 for elafin and 0.75 for the combination of ST2 and REG3α. The addition of elafin to the other 2 biomarkers did not improve the AUC. Our data indicate that serum elafin concentrations measured at the initiation of systemic treatment for acute GVHD did not predict 6-month NRM, OS, or treatment response in a multicenter population of patients treated systemically for acute GVHD. As seen in previous studies, serum concentrations of the GI GVHD biomarkers ST2 and REG3α were significant predictors of NRM, and the addition of elafin levels did not improve their accuracy. These results underscore the importance of GI disease in driving NRM in patients who develop acute GVHD.
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Affiliation(s)
- Makda Getachew Zewde
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - George Morales
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Isha Gandhi
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Umut Özbek
- Biostatistics Shared Resource Facility, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Paibel Aguayo-Hiraldo
- Children's Center for Cancer and Blood Diseases, Blood and Marrow Transplantation Section, Children's Hospital Los Angeles, Los Angeles, California
| | - Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Center, Hamburg-Eppendorf, Germany
| | - Janna Baez
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | | | - Hannah Choe
- Blood and Marrow Transplantation Program, Ohio State University, Columbus, Ohio
| | - Zachariah DeFilipp
- Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, Massachusetts
| | - Aaron Etra
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Stephan Grupp
- Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Elizabeth O Hexner
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
| | - William Hogan
- Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, Minnesota
| | - Nora Rebeka Javorniczky
- Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
| | - Stelios Kasikis
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Carrie L Kitko
- Pediatric Blood and Marrow Transplantation Program, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Steven Kowalyk
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Elisabeth Meedt
- Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany
| | - Pietro Merli
- Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, Italy
| | - Ryotaro Nakamura
- Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California
| | - Muna Qayed
- Pediatric Blood and Marrow Transplantation Program, Aflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, Atlanta
| | - Ran Reshef
- Blood and Marrow Transplantation Program, Columbia University, New York, New York
| | - Wolf Rösler
- Department of Internal Medicine 5, Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany
| | - Tal Schechter
- Division of Hematology/Oncology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Daniela Weber
- Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany
| | - Matthias Wölfl
- Pediatric Blood and Marrow Transplantation Program, Children's Hospital, University of Würzburg, Würzburg, Germany
| | - Gregory Yanik
- Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan
| | - Rachel Young
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - John E Levine
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - James L M Ferrara
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Yi-Bin Chen
- Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, Massachusetts
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Kurosawa S, Yamaguchi T, Mori A, Tsukagoshi M, Okuda I, Kayama M, Fuji S, Yamashita T, Ogawa C, Ito A, Tanaka T, Inamoto Y, Kim SW, Fukuda T. Prognostic Impact of Pretransplantation Quality of Life and Its Post-Transplantation Longitudinal Change after Allogeneic Hematopoietic Cell Transplantation: A Prospective Study That Administered the Short-Form Health Survey (SF-12) and EuroQol 5. Transplant Cell Ther 2021; 27:935.e1-935.e9. [PMID: 34371214 DOI: 10.1016/j.jtct.2021.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/27/2021] [Accepted: 07/29/2021] [Indexed: 11/15/2022]
Abstract
In allogeneic hematopoietic cell transplantation (allo-HCT), investigator-based clinical variables have been used for pretransplantation prognostic prediction, risk adjustment, and post-transplantation long-term screenings. Although several studies have investigated the prognostic significance of pretransplantation patient-reported outcomes (PROs) and longitudinal trends in PROs after allo-HCT, few have assessed these outcomes using the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) and EuroQol 5 Dimension (EQ-5D) index. The present study used 18 items from the SF-12 and EQ-5D index to evaluate the prognostic impact of pretransplantation quality of life (QOL) on allo-HCT outcomes and longitudinal changes in QOL in allo-HCT recipients. This single-center prospective study included consecutive patients who underwent allo-HCT at our center between October 2014 and September 2016. All participants were followed up until October 2017. The SF-12 and EQ-5D index were administered to assess patient-reported QOL before allo-HCT and at 3 months, 6 months, 1 year, and 2 years after allo-HCT when participants visited the long-term follow-up clinic. Longitudinal trends in the QOL-adjusted means were estimated using linear mixed-effects, adjusting for pretransplantation covariates and reasons for missing QOL data. Among 157 patients who underwent allo-HCT, 145 (92%) were registered in this study, and 143 with available QOL data were analyzed. The median pretransplantation scores were 45.3 for the SF-12 physical component score (PCS), 55.6 for the mental component score (MCS), 38.8 for the role/social component score (RCS), 70.0 for the visual analog scale (VAS), and 49.0 for the EQ-5D index. Overall survival (OS) was significantly improved in patients with higher pretransplantation scores on the PCS, RCS, and EQ-5D index, and multivariable analyses showed that the median pretransplantation RCS was significantly associated with OS after allo-HCT (hazard ratio, 3.66; P = .003). The longitudinal trends in the SF-12 score showed that the PCS was improved at 2 years after allo-HCT and was comparable to the normative score for the general population. The MCS remained comparable to or higher than the normative score after allo-HCT. The RCS improved significantly beginning at 6 months after allo-HCT but remained lower than the normative score at 2 years. The VAS and EQ-5D index values showed a drop at 3 months after allo-HCT. Patient-reported QOL assessed by 18 questions on the SF-12 and EQ-5D predicted prognosis, and may be used as a prognosticator to determine treatment strategies, including preparative regimens. Although we experienced a certain amount of patient attrition in the longitudinal follow-up of QOL data, we demonstrated characteristic trajectories of QOL in different domains after adjusting for background covariates and reasons for the lack of QOL data. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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Affiliation(s)
- Saiko Kurosawa
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan; Department of Oncology, Ina Central Hospital, Ina, Japan.
| | - Takuhiro Yamaguchi
- Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ayako Mori
- Nursing Division, National Cancer Center Hospital, Tokyo, Japan
| | - Mayumi Tsukagoshi
- Nursing Division, National Cancer Center Hospital, Tokyo, Japan; Nursing Division, International University of Health and Welfare Hospital, Tochigi, Japan
| | - Ikue Okuda
- Nursing Division, National Cancer Center Hospital, Tokyo, Japan
| | - Masako Kayama
- Nursing Division, National Cancer Center Hospital, Tokyo, Japan
| | - Shigeo Fuji
- Department of Hematology, Osaka International Cancer Institute, Osaka, Japan
| | - Takuya Yamashita
- Department of Hematology, St. Luke's International Hospital, Tokyo, Japan
| | - Chitose Ogawa
- Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Ayumu Ito
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Takashi Tanaka
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshihiro Inamoto
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Sung-Won Kim
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Fukuda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
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Janicsák H, Ungvari GS, Gazdag G. Psychosocial aspects of hematopoietic stem cell transplantation. World J Transplant 2021; 11:263-276. [PMID: 34316451 PMCID: PMC8290998 DOI: 10.5500/wjt.v11.i7.263] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/18/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) has become a conventional and potentially curative treatment for various hematological diseases. As more sophisticated procedures have been developed and mortality rates have decreased, attention has shifted to the psychosocial challenges associated with transplantation. The psychosocial difficulties accompanying transplantation are addressed in the context of both quality of life (QOL) and psychopathological research. Among the psychiatric comorbidities of HSCT, anxiety, depression, sleep and sexual disorders, delirium and post-traumatic stress disorder are the most studied conditions. Recently, more attention has been focused on the psychosocial burden of caregivers. Devising recommendations for the management of psychiatric symptoms and psychosocial interventions in HSCT sufferers and close relatives is a major concern to consultation-liaison psychiatrists and transplant teams. This review synthesizes and critically evaluates the current literature on the psychosocial aspects of HSCT and appraises the clinical significance of these outcomes. Issues of QOL assessment; psychosocial functioning and QOL in the course of HSCT; impact of graft-versus-host disease and other predictors of QOL and psychosocial functioning; comorbid psychiatric disorders; and interventions to maintain or improve QOL and reduce psychopathology and psychosocial burden on family members are presented.
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Affiliation(s)
- Henrietta Janicsák
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
| | - Gabor S Ungvari
- Division of Psychiatry, University of Notre Dame, Fremantle 6009, Australia
- Division of Psychiatry, School of Medicine, University of Western Australia, Perth 6009, Australia
| | - Gábor Gazdag
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Budapest 1083, Hungary
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46
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Abo S, Ritchie D, Denehy L, Panek-Hudson Y, Irving L, Granger CL. Feasibility of early-commencing group-based exercise in allogeneic bone marrow transplantation: the BOOST study. Bone Marrow Transplant 2021; 56:2788-2796. [PMID: 34272484 DOI: 10.1038/s41409-021-01411-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/27/2021] [Accepted: 07/05/2021] [Indexed: 01/06/2023]
Abstract
Increasing evidence supports that individualised exercise is safe and beneficial for adults treated with allogeneic bone marrow transplantation (alloBMT), although this is not part of standard care and no research has investigated group-based interventions. This study aimed to determine safety, feasibility and exploratory effects of a supervised group-based inpatient and subsequent home-based exercise programme in alloBMT. This single-site prospective cohort study included consecutive adults treated with alloBMT for haematological disease. All participants received usual care in addition to the protocolised exercise programme pre-transplant until 60 days post transplant. The primary outcome was feasibility; secondary outcomes included exercise capacity, frailty, health-related quality of life and strength. Consent rate was 100% (n = 42); 83% (n = 35) completed all aspects of the intervention and outcome testing; of those, 83% (n = 29) attended ≥2 group-exercise sessions per week; no adverse events occurred. Emotional well-being significantly improved over time, which may highlight benefits of group-based intervention. Other outcomes significantly declined from pre-BMT to hospital discharge, with some improvement at 60 days post-BMT. Participants with early signs of frailty demonstrated the greatest decline in outcomes. Group-based exercise was safe and feasible; observations from this study highlight the importance of baseline identification of frailty to target intervention at those who need it most.
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Affiliation(s)
- Shaza Abo
- Department of Physiotherapy, The University of Melbourne, Melbourne, VIC, Australia. .,Department of Physiotherapy, Royal Melbourne Hospital, Parkville, VIC, Australia.
| | - David Ritchie
- Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Linda Denehy
- Department of Physiotherapy, The University of Melbourne, Melbourne, VIC, Australia.,Department of Allied Health, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Yvonne Panek-Hudson
- Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Louis Irving
- Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Catherine L Granger
- Department of Physiotherapy, The University of Melbourne, Melbourne, VIC, Australia.,Department of Physiotherapy, Royal Melbourne Hospital, Parkville, VIC, Australia
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47
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Sun YC, Inamoto Y, Wang RK, Lee SJ, Hung KF, Shen TT. The disposable bandage soft contact lenses therapy and anterior segment optical coherence tomography for management of ocular graft-versus-host disease. BMC Ophthalmol 2021; 21:271. [PMID: 34217260 PMCID: PMC8254955 DOI: 10.1186/s12886-021-02031-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 06/04/2021] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To identify the ocular surface changes of ocular graft-versus-host disease (GVHD) using anterior segment optical coherence tomography (AS-OCT) and examine the efficacy of disposable bandage soft contact lens (BSCL) treatment in ocular GVHD patients. METHODS This study is a prospective, Phase II clinical trial. Nineteen patients diagnosed with chronic GVHD based on the NIH criteria and ocular symptoms of NIH eye score 2 or greater were enrolled. Disposable BSCL was applied to the GVHD-affected eyes with topical antibiotic coverage. Ocular exams, eye symptom surveys, and AS-OCT were performed with signed informed consent. Patients were followed for one to three months. RESULTS Thirty-eight eyes of 19 patients with ocular GVHD underwent BSCL treatment in this study. AS-OCT scans were done in 14 out of 19 patients. The mean best-corrected visual acuity at enrollment, 2-week, and 4-week visits was 0.180, 0.128, and 0.163 logMAR, respectively. Twenty-four out of 25 eyes (96 %) that initially presented with conjunctival inflammation, twenty-three out of 30 eyes (76.7 %) that initially presented with punctate epithelial erosion, and 8 out of 15 (53.3 %) eyes that initially presented with filamentous keratopathy showed improvement after wearing BSCL for 2 to 4 weeks. AS-OCT revealed corneal epithelial irregularity, abnormal meibomian gland orifice, and conjunctival hyperemia, in patients with ocular GVHD. CONCLUSIONS BSCL treatment provided significant subjective and objective improvements in ocular GVHD patients. Meanwhile, we found that AS-OCT can be a promising diagnostic tool to characterize the ocular surface changes associated with ocular GVHD.
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Affiliation(s)
- Yi-Chen Sun
- Department of Ophthalmology, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.,Department of Ophthalmology, University of Washington, 1959 NE Pacific St, Washington, Seattle, USA
| | - Yoshihiro Inamoto
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.,Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Ruikang K Wang
- Department of Bioengineering, University of Washington, Seattle, Washington, USA
| | - Stephanie J Lee
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Kai-Feng Hung
- Department of Medical Research, Division of Translational Research, Taipei Veterans General Hospital, No.201, Sec 2, Shipai Rd., Beitou District, Taipei, Taiwan. .,Department of Dentistry, School of Dentistry, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
| | - Tueng T Shen
- Department of Ophthalmology, University of Washington, 1959 NE Pacific St, Washington, Seattle, USA.
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48
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Pukhalskaya T, Smoller BR, Becker M, Maly A, Zadik Y, Elad S. Oral white lesion in patients post-hematopoietic stem cell transplantation: a case series demonstrating the diagnostic dilemma. Support Care Cancer 2021; 29:7999-8007. [PMID: 34218349 DOI: 10.1007/s00520-021-06392-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 06/23/2021] [Indexed: 10/20/2022]
Abstract
The current National Institutes of Health (NIH) consensus paper excluded "white hyperkeratotic plaque" from the diagnostic criteria for oral chronic graft-versus-host disease (cGVHD) in order to ensure malignant transformation is not overlooked. Therefore, an isolated oral white plaque is recommended to be subjected to biopsy and pathologic examination. The cases described in this paper shed a new light on the clinical approach to oral white plaque post-hematopoietic stem cell transplantation. The objectives of this article are to demonstrate that a white plaque does not contradict a diagnosis of oral cGVHD, and to highlight the clinical considerations for taking a biopsy.
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Affiliation(s)
- Tatsiana Pukhalskaya
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY, 14642, USA.
| | - Bruce R Smoller
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY, 14642, USA
| | - Michael Becker
- Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
| | - Alexander Maly
- Department of Pathology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
| | - Yehuda Zadik
- Department of Military Medicine, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Sharon Elad
- Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA
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Doki N, Toyosaki M, Shiratori S, Osumi T, Okada M, Kawakita T, Sawa M, Ishikawa T, Ueda Y, Yoshinari N, Nakahara S. An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease. Transplant Cell Ther 2021; 27:867.e1-867.e9. [PMID: 34102349 DOI: 10.1016/j.jtct.2021.05.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/20/2021] [Accepted: 05/24/2021] [Indexed: 12/30/2022]
Abstract
Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. There are no well-established treatment options for cGVHD after primary steroid-based treatment. Ibrutinib showed clinical benefit with an acceptable safety profile in steroid-dependent/refractory cGVHD patients in a Phase 1b/2 study (PCYC-1129-CA, NCT02195869), with which it was approved in the United States for adult cGVHD patients after failure of ≥1 systemic treatments. This open-label, single-arm, multicenter study was conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ibrutinib in Japanese patients ≥12 years of age with steroid-dependent/refractory cGVHD (NCT03474679). Patients were assessed on the basis of the National Institutes of Health (NIH) Consensus Development Project Criteria for Clinical Trials in cGVHD (2014). All patients received ibrutinib at a dose of 420 mg orally once daily, with a dose reduction to 280 mg/d on the concomitant use of voriconazole. Nineteen patients, including 1 adolescent, were enrolled and treated with ibrutinib in the study. At the time of clinical data cutoff (when the last patient completed the efficacy assessment at week 37), 10 of 19 patients (52.6%) remained on treatment whereas 9 of 19 patients (47.4%) had discontinued ibrutinib. The median duration of ibrutinib treatment was 9.63 (range 0.6 to 16.7+) months. The best overall response rate was 73.7%, and the rate of sustained response for ≥20 weeks was 71.4% for the responders (52.6% of all patients). Responses were seen across all the involved organs for cGVHD. Median daily corticosteroid dose requirement decreased by 0.06 mg/kg/d from baseline to week 36, whereas an improvement in the Lee cGVHD Symptom Scale score was observed in 42.1% of patients. The most common treatment-emergent adverse events (TEAEs) were pneumonia and stomatitis (36.8% each), upper respiratory tract infection (31.6%), cellulitis and platelet count decreased (26.3% each), and nausea (21.1%). Furthermore, 11 of 19 patients (57.9%) were reported with ≥1 treatment-emergent serious adverse events; the most common being pneumonia (26.3%) and cellulitis (15.8%). In total, 4 of 19 patients (21.1%) died during the study, of which 3 of 19 patients (15.8%) had TEAEs leading to death whereas 1 patient died of peritonitis, which occurred >30 days after the last dose of ibrutinib. Treatment-emergent adverse events leading to ibrutinib discontinuation were reported in 3 of 19 patients (15.8%). Ibrutinib was rapidly absorbed with a median time to reach maximum plasma concentration (tmax) of ~4.0 hours. Steady-state exposures were ~3.0- and ~1.4-fold higher for the patients receiving fluconazole (n = 8) and voriconazole (n = 4) with ibrutinib, respectively, as compared with patients not receiving CYP3A inhibitors (n = 7). Mean Bruton's tyrosine kinase occupancy was 88.1% at 4 hours after dose on day 1, and occupancy levels were maintained throughout the assessment period, regardless of the ibrutinib daily dose. Ibrutinib showed a clinically meaningful response and an acceptable safety profile in Japanese patients with steroid-dependent/refractory cGVHD; the safety profile was consistent with the known safety profile of ibrutinib in adults and with that seen in cGVHD patients receiving concomitant steroid treatment. Overall, the results were generally consistent with findings observed in the PCYC-1129-CA study.
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Affiliation(s)
- Noriko Doki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
| | - Masako Toyosaki
- Division of Hematology/Oncology Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan
| | - Souichi Shiratori
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Tomoo Osumi
- Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Masaya Okada
- Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Toshiro Kawakita
- Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Takayuki Ishikawa
- Department of Hematology, Kobe City Medical Center General Hospital, Hyogo, Japan
| | - Yasunori Ueda
- Department of Hematology/Oncology, Kurashiki Central Hospital, Kurashiki, Japan
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A phase 2 trial of GVHD prophylaxis with PTCy, sirolimus, and MMF after peripheral blood haploidentical transplantation. Blood Adv 2021; 5:1154-1163. [PMID: 33635333 DOI: 10.1182/bloodadvances.2020003779] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/13/2021] [Indexed: 12/14/2022] Open
Abstract
The introduction of posttransplant cyclophosphamide (PTCy) made performing allogeneic hematopoietic cell transplantation (HCT) from HLA haplotype-incompatible donors possible. In a setting of PTCy and tacrolimus/mycophenolate mofetil (MMF) as a graft-versus-host disease (GVHD) prophylaxis, a peripheral blood (PB) graft source as compared with bone marrow reduces the relapse rate but increases acute GVHD (aGVHD) and chronic GVHD (cGVHD). This phase 2 trial assessed sirolimus and MMF efficacy following PTCy as a GVHD prophylaxis after PB haploidentical HCT (haplo-HCT). With 32 evaluable patients (≥18 years) enrolled, this study had 90% power to demonstrate a reduction in 100-day grade II-IV aGVHD to 20% from the historical benchmark of 40% after haplo-HCT using PTCy/tacrolimus/MMF. At a median follow-up of 16.1 months, the primary end point of the trial was met with a day-100 grade II-IV aGVHD cumulative incidence of 18.8% (95% confidence interval [CI], 7.5% to 34.0%). There were no graft-failure events and the 1-year probability of National Institutes of Health (NIH) moderate/severe cGVHD was 18.8% (95% CI, 7.4% to 34.0%), nonrelapse mortality was 18.8% (95% CI, 7.4% to 34.0%), relapse was 22.2% (95% CI, 9.6% to 38.2%), disease-free survival was 59.0% (95% CI, 44.1% to 79.0%), GVHD-free relapse-free survival was 49.6% (95% CI, 34.9% to 70.5%), and overall survival was 71.7% (95% CI, 57.7% to 89.2%) for the entire cohort. These data demonstrate that GVHD prophylaxis with sirolimus/MMF following PTCy effectively prevents grade II-IV aGVHD after PB haplo-HCT, warranting prospective comparison of sirolimus vs tacrolimus in combination with MMF following PTCy as GVHD prophylaxis after PB HCT. This trial was registered at www.clinicaltrials.gov as #NCT03018223.
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