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Chalandon Y, Devillier R, Boumendil A, Nguyen S, Bulabois CE, Ceballos P, Brissot E, Rubio MT, Labussière-Wallet H, Maertens J, Chevallier P, Maillard N, Poiré X, Castilla-Llorente C, Beguin Y, Cornillon J, Maury S, Marchand T, Daguindau E, Bay JO, Turlure P, Joris M, Menard AL, Bilger K, Guillerm G, François S, Bazarbachi A, Chantepie S, Lewalle P, Marçais A, Loschi M, Benakli M, Chauvet P, Forcade E, Huynh A, Robin M, Masouridi-Levrat S. Allogeneic Hematopoietic Stem Cell Transplantation for Elderly Acute Lymphoblastic Leukemia Patients: A Registry Study From the Société Francophone de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC). Am J Hematol 2025. [PMID: 40326583 DOI: 10.1002/ajh.27701] [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: 01/24/2025] [Revised: 03/29/2025] [Accepted: 04/19/2025] [Indexed: 05/07/2025]
Abstract
There are very limited data regarding the outcomes of elderly patients with acute lymphoblastic leukemia (ALL) who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). A total of 316 ALL patients aged ≥ 60 years who underwent alloHSCT between 2010 to 2022 were identified in the SFGM-TC registry. The primary objective was to evaluate progression-free survival (PFS), non-relapse mortality (NRM), relapse incidence (RI), and graft-versus-host disease (GvHD)-free relapse-free survival (GRFS), as well as their risk factors. The median age was 63.8 years (range 60-75.8), 49.8% of patients had Philadelphia-positive B-ALL (Ph + ALL), and 70.9% were in first complete remission (CR1) at transplantation. The donor was an unrelated donor in 52.1%, a matched related donor (MRD) in 26.3%, and a haplo-identical donor in 17.7%. Reduced-intensity conditioning (RIC) was administered to 64.6% of patients, while total body irradiation (TBI) was used in 35.8%. The 3-year overall survival (OS) was 46% (95% CI 40%-53%). The 3-year PFS, NRM, RI, and GRFS were 41% (95% CI 35%-48%), 23% (95% CI 18%-28%), 36% (95% CI 31%-42%), and 30% (95% CI 25%-37%), respectively. Multivariable analyses confirmed poorer OS and PFS in patients with advanced disease, with an HR of 1.79 (95% CI 1.22-2.64), p = 0.0032. Additionally, the ALL subtype significantly impacted outcomes, with an HR of 1.99 (95% CI 1.42-2.79) for non-Ph + ALL. This study suggests that alloHSCT is a viable option for elderly ALL patients, as age itself did not impact outcomes. However, advanced disease and non-Ph + ALL were associated with significantly worse survival.
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Affiliation(s)
- Yves Chalandon
- University Hospital Geneva, Hematology Service and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | | | | | | | | | | | - Eolia Brissot
- Sorbonne Université, INSERM UMRs938, Paris, France, Service d'Hématologie Clinique et de Thérapie Cellulaire, Paris, France
| | | | | | | | | | | | - Xavier Poiré
- Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | | | | | | | | | | | | | | | - Pascal Turlure
- Clinical Hematology, Limoges University Hospital, Limoges, France
| | | | | | | | | | | | - Ali Bazarbachi
- BMT Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | | | - Philippe Lewalle
- Hematology Department, Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium
| | | | | | | | - Paul Chauvet
- CHU de Lille, Maladies du Sang, Université de Lille, Lille, France
| | - Edouard Forcade
- Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, Bordeaux, France
| | - Anne Huynh
- CHU Toulouse, IUCT Oncopôle, Toulouse, France
| | - Marie Robin
- Hôpital Saint-Louis, APHP, Université de Paris Cité, Paris, France
| | - Stavroula Masouridi-Levrat
- University Hospital Geneva, Hematology Service and Faculty of Medicine, University of Geneva, Geneva, Switzerland
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2
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Swoboda R, Labopin M, Giebel S, Maertens J, Parovichnikova E, Versluis J, Pavlu J, Kopinska A, Capria S, Raida L, Rambaldi A, Caillot D, Folber F, Nachbaur D, Ozturk M, Aljurf M, Rubio MT, Gorin NC, Lanza F, Nagler A, Mohty M, Ciceri F. Autologous stem cell transplantation for adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission. A study by the Acute Leukemia Working Party of the EBMT. BMC Cancer 2025; 25:787. [PMID: 40289118 PMCID: PMC12036279 DOI: 10.1186/s12885-025-14126-8] [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: 09/26/2024] [Accepted: 04/09/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND The role of autologous hematopoietic stem cell transplantation (AHSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL) remains controversial. The aim of this retrospective study was to analyze results of AHSCT and to identify prognostic factors. METHODS Overall, 700 patients transplanted in first complete remission between the years 1999-2020 were included. Median patient age was 31.9 years (68% male). B-cell precursor ALL (BCP-ALL) and T-cell precursor ALL (TCP-ALL) was diagnosed in 35% and 65%, respectively. Among 190 patients with available data, negative minimal residual disease (MRD) status was reported in 167 (88%) cases. RESULTS The probabilities of overall survival (OS) and leukemia-free survival (LFS) at 2 years were 67% and 56%; relapse incidence (RI) and non-relapse mortality (NRM) were 39% and 5%, respectively. TCP-ALL was associated with lower RI (41% vs. 56%, p=0.001), higher LFS (52% vs. 38%, p=0.002) and OS (58% vs 45%, p=0.001) at 5 years when compared to BCP-ALL. In the multivariate analysis, TCP-ALL and longer interval from diagnosis do AHSCT were associated with reduced risk of relapse (HR 0.7, p=0.006 and HR=0.95, p=0.018), better LFS (HR=0.76, p=0.02 and HR=0.95, p=0.01) and OS (HR=0.75, p=0.024 and HR=0.94, p=0.013, respectively). Increasing patient age was associated with higher NRM (HR=1.49, p<0.0001), worse LFS (HR=1.1, p=0.01) and OS (HR=1.17, p=0.0001). CONCLUSIONS Autologous hematopoietic stem cell transplantation is relatively safe option of late treatment intensification in adults with Ph- ALL. It may be a valuable option especially in patients with TCP-ALL, however it should be proved in prospective clinical trials.
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Affiliation(s)
- Ryszard Swoboda
- Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Str. Wybrzeze Armii Krajowej 15, Gliwice, 44-101, Poland.
| | - Myriam Labopin
- Department of Hematology and Cellular Therapy, National Institute of Health and Medical Research Unit UMR-S 938, Sorbonne University and St Anthony Scientific Research Center, Public Assistance Hospital of Paris, St Anthony Hospital, Paris, France
- European Society for Blood and Marrow Transplantation Paris Study Office/CEREST-TC, Paris, France
| | - Sebastian Giebel
- Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Str. Wybrzeze Armii Krajowej 15, Gliwice, 44-101, Poland
| | - Johan Maertens
- Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium
| | - Elena Parovichnikova
- National Research Center for Hematology, Bone Marrow Transplantation, Moscow, Russian Federation
| | - Jurjen Versluis
- Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jiri Pavlu
- Department of Haematology, Imperial College, Hammersmith Hospital, London, UK
| | - Anna Kopinska
- Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland
| | - Saveria Capria
- Univ. La Sapienza, Dip. Biotecnologie Cellulari ed Ematologia, Rome, Italy
| | - Ludek Raida
- Department of Haemato-Oncology, Olomouc University Hospital and Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
| | - Alessandro Rambaldi
- Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Milan, Italy
| | - Denis Caillot
- Hopital d'Enfants, CHU de Dijon, Service Hematologie Adultes, Dijon, France
| | - Frantisek Folber
- Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital Brno, Brno, Czech Republic
| | - David Nachbaur
- Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, Anichstrasse 35, Innsbruck, A- 6020, Austria
| | - Mustafa Ozturk
- GATA BMT Center, Gülhane Military Medical Academy, Ankara, Turkey
| | - Mahmoud Aljurf
- King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | | | | | - Francesco Lanza
- Hematology Unit, University Hospital and Romagna Transplant Network, Ravenna, University of Bologna, Bologna, Italy
| | - Arnon Nagler
- Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel
| | - Mohamad Mohty
- Department of Hematology and Cellular Therapy, National Institute of Health and Medical Research Unit UMR-S 938, Sorbonne University and St Anthony Scientific Research Center, Public Assistance Hospital of Paris, St Anthony Hospital, Paris, France
- European Society for Blood and Marrow Transplantation Paris Study Office/CEREST-TC, Paris, France
| | - Fabio Ciceri
- Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy
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Stella D, Gill J, Passera R, Zompi S, Dellacasa CM, Audisio E, Cerrano M, Dogliotti I, Dicataldo M, Secreto C, Bruno B, Freilone R, Busca A, Giaccone L. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia: Results of a Single-Center Study. Hematol Rep 2024; 16:636-647. [PMID: 39449305 PMCID: PMC11503301 DOI: 10.3390/hematolrep16040062] [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: 08/12/2024] [Revised: 10/01/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Despite the adoption of pediatric-like chemotherapy protocols, the introduction of new immunotherapies and a better understanding of the oncogenic landscape, the outcome for adult patients with acute lymphoblastic leukemia (ALL) remain substantially dismal. The aim of the present study was to evaluate the outcome in terms of survival in a cohort of adult patients with ALL who received allogeneic hematopoietic stem cell transplantation (alloSCT) between 2013 and 2023. METHODS This was a single-center observational retrospective study including all consecutive adult patients with ALL who received an alloSCT between April 2013 and April 2023 at the Stem Cell Transplant Center AOU Città della Salute e della Scienza of Torino. The primary endpoints were overall survival (OS), graft-versus-host disease (GVHD) Relapse-Free Survival (GRFS), Leukemia-Free Survival (LFS) and cumulative incidence (CI) of Non-Relapse Mortality (NRM). RESULTS The 4-year OS and LFS were 63.4% and 48.1%, respectively, and the 1-year GRFS was 42.9%. The 1-year CI of bloodstream infections (BSI), invasive fungal infections and NRM were 38%, 7% and 18.4%, respectively. Multivariate analysis showed that the use of total body irradiation (TBI), a time interval from diagnosis to alloSCT 7 months and female gender were factors significantly associated with better OS. Relapse of the underlying malignancy and BSI were the main causes of death. CONCLUSION Our study suggests that alloSCT from a matched sibling donor (MSD) and alternative donors may be considered an effective tool for patients with ALL achieving a CR.
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Affiliation(s)
- Davide Stella
- Department of Molecular Biotechnology and Health Sciences, Division of Hematology, University of Torino, 10126 Torino, Italy; (D.S.)
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Jessica Gill
- Department of Molecular Biotechnology and Health Sciences, Division of Hematology, University of Torino, 10126 Torino, Italy; (D.S.)
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Roberto Passera
- Senior Biostatistician, Department of Medical Sciences, A.O.U. Città della Salute e della Scienza di Torino, University of Torino, 10126 Torino, Italy
| | - Sofia Zompi
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Chiara Maria Dellacasa
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Ernesta Audisio
- Department of Oncology, Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy
| | - Marco Cerrano
- Department of Oncology, Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy
| | - Irene Dogliotti
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Michele Dicataldo
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Carolina Secreto
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Benedetto Bruno
- Department of Molecular Biotechnology and Health Sciences, Division of Hematology, University of Torino, 10126 Torino, Italy; (D.S.)
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Roberto Freilone
- Department of Oncology, Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy
| | - Alessandro Busca
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
| | - Luisa Giaccone
- Department of Molecular Biotechnology and Health Sciences, Division of Hematology, University of Torino, 10126 Torino, Italy; (D.S.)
- Stem Cell Transplant Center, A.O.U. Città della Salute e della Scienza di Torino, 10126 Torino, Italy (M.D.)
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Yuan X, Yang Y, Wang C, Wang Y, Chen J, Wu Y, Hu R. Decision-making conflicts regarding hematopoietic stem cell transplantation in patients with hematological neoplasms: A descriptive qualitative study. Eur J Oncol Nurs 2024; 72:102684. [PMID: 39163755 DOI: 10.1016/j.ejon.2024.102684] [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: 12/04/2023] [Revised: 08/01/2024] [Accepted: 08/14/2024] [Indexed: 08/22/2024]
Abstract
PURPOSE To explore and understand the conflict in decision-making of hematopoietic stem cell transplantation in patients with hematological neoplasms. METHODS A descriptive qualitative study of 16 patients with hematologic neoplasms in the hematology department was conducted between February 2022 and May 2022. Purposive sampling was used to select participants. Face-to-face in-depth personal interviews were performed. Interviews were recorded, transcribed, and coded. This descriptive qualitative study adhered to the COREQ checklist. RESULTS All patients indicated difficulties in making decisions regarding hematopoietic stem cell transplantation. Five themes were identified: (1) weighing the pros and cons of HSCT, (2) financial burden versus desire for rebirth, (3) treatment urgency versus being unprepared, (4) saving oneself versus damaging loved ones, and (5) family companionship versus emotional isolation. These themes reflect the contradictions, entanglements, and realistic conflicts in decision-making regarding hematopoietic stem cell transplantation for patients with hematological neoplasms. CONCLUSIONS This study identified multiple conflicts of decision-making in patients with hematologic neoplasms regarding decisions on hematopoietic stem cell transplantations. Healthcare workers should provide patients with disease knowledge, doctor-patient and intra-family communication, and access to financial support in order to resolve their conflicts and ultimately help them make the decision that is most optimum for them.
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Affiliation(s)
- Xiaohuan Yuan
- The School of Nursing, Fujian Medical University, Fujian Province, China.
| | - Yidan Yang
- The School of Nursing, Fujian Medical University, Fujian Province, China.
| | - Chunfeng Wang
- The School of Nursing, Fujian Medical University, Fujian Province, China.
| | - Ying Wang
- The School of Nursing, Fujian Medical University, Fujian Province, China.
| | - Jingyi Chen
- The School of Nursing, Fujian Medical University, Fujian Province, China.
| | - Yong Wu
- Department of Hematology, Fujian Medical University Union Hospital, Fujian Province, China.
| | - Rong Hu
- The School of Nursing, Fujian Medical University, Fujian Province, China.
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Jing J, Ma Y, Xie Z, Wang B, Chen Y, Chi E, Wang J, Zhang K, Wang Z, Li S. Acute T-cell lymphoblastic leukemia: chimeric antigen receptor technology may offer a new hope. Front Immunol 2024; 15:1410519. [PMID: 39192970 PMCID: PMC11347323 DOI: 10.3389/fimmu.2024.1410519] [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: 04/01/2024] [Accepted: 07/15/2024] [Indexed: 08/29/2024] Open
Abstract
Acute lymphoblastic leukemia (ALL) is a prevalent malignancy affecting the hematopoietic system, encompassing both B-cell ALL (B-ALL) and T-cell ALL (T-ALL). T-ALL, characterized by the proliferation of T-cell progenitors in the bone marrow, presents significant treatment challenges, with patients often experiencing high relapse rates and poor long-term survival despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT). This review explores the pathogenesis and traditional treatment strategies of T-ALL, emphasizing the promising potential of chimeric antigen receptor (CAR) technology in overcoming current therapeutic limitations. CAR therapy, leveraging genetically modified immune cells to target leukemia-specific antigens, offers a novel and precise approach to T-ALL treatment. The review critically analyzes recent developments in CAR-T and CAR-NK cell therapies, their common targets, optimization strategies, clinical outcomes, and the associated challenges, providing a comprehensive overview of their clinical prospects in T-ALL treatment.
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Affiliation(s)
- Jiajie Jing
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Yuan Ma
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Ziwen Xie
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Bingyan Wang
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Yueming Chen
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Enjie Chi
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Jiadong Wang
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Kejin Zhang
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
| | - Zhujun Wang
- Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Sisi Li
- Department of Clinical Medicine, Hangzhou City University School of Medicine, Hangzhou, China
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6
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Hermans SJF, van Norden Y, Versluis J, Rijneveld AW, van der Holt B, de Weerdt O, Biemond BJ, van de Loosdrecht AA, van der Wagen LE, Bellido M, van Gelder M, van der Velden WJFM, Selleslag D, van Lammeren‐Venema D, van der Velden VHJ, de Wreede LC, Postmus D, Pignatti F, Cornelissen JJ. Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi-state modeling. Cancer Med 2024; 13:e6756. [PMID: 38680089 PMCID: PMC11056700 DOI: 10.1002/cam4.6756] [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: 08/04/2023] [Revised: 10/13/2023] [Accepted: 11/15/2023] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND We recently reported results of the prospective, open-label HOVON-100 trial in 334 adult patients with acute lymphoblastic leukemia (ALL) randomized to first-line treatment with or without clofarabine (CLO). No improvement of event-free survival (EFS) was observed, while a higher proportion of patients receiving CLO obtained minimal residual disease (MRD) negativity. AIM In order to investigate the effects of CLO in more depth, two multi-state models were developed to identify why CLO did not show a long-term survival benefit despite more MRD-negativity. METHODS The first model evaluated the effect of CLO on going off-protocol (not due to refractory disease/relapse, completion or death) as a proxy of severe treatment-related toxicity, while the second model evaluated the effect of CLO on obtaining MRD negativity. The subsequent impact of these intermediate events on death or relapsed/refractory disease was assessed in both models. RESULTS Overall, patients receiving CLO went off-protocol more frequently than control patients (35/168 [21%] vs. 18/166 [11%], p = 0.019; HR 2.00 [1.13-3.52], p = 0.02), especially during maintenance (13/44 [30%] vs. 6/56 [11%]; HR 2.85 [95%CI 1.08-7.50], p = 0.035). Going off-protocol was, however, not associated with more relapse or death. Patients in the CLO arm showed a trend towards an increased rate of MRD-negativity compared with control patients (HR MRD-negativity: 1.35 [0.95-1.91], p = 0.10), which did not translate into a significant survival benefit. CONCLUSION We conclude that the intermediate states, i.e., going off-protocol and MRD-negativity, were affected by adding CLO, but these transitions were not associated with subsequent survival estimates, suggesting relatively modest antileukemic activity in ALL.
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Affiliation(s)
| | - Yvette van Norden
- Erasmus University Medical Center Cancer InstituteRotterdamThe Netherlands
- HOVON FoundationRotterdamThe Netherlands
| | - Jurjen Versluis
- Erasmus University Medical Center Cancer InstituteRotterdamThe Netherlands
| | - Anita W. Rijneveld
- Erasmus University Medical Center Cancer InstituteRotterdamThe Netherlands
| | | | - Okke de Weerdt
- Department of HematologySint Antonius HospitalNieuwegeinThe Netherlands
| | - Bart J. Biemond
- Department of HematologyAmsterdam University Medical Centers, Amsterdam Medical CenterAmsterdamThe Netherlands
| | - Arjan A. van de Loosdrecht
- Department of HematologyCancer Center Amsterdam, Amsterdam University Medical Centers, Vrije Universiteit University Medical CenterAmsterdamThe Netherlands
| | | | - Mar Bellido
- Department of HematologyUniversity Medical Center GroningenGroningenThe Netherlands
| | - Michel van Gelder
- Department of HematologyMaastricht University Medical CenterMaastrichtThe Netherlands
| | | | | | | | | | - Liesbeth C. de Wreede
- Department of Biomedical Data SciencesLeiden University Medical CenterLeidenThe Netherlands
| | - Douwe Postmus
- Department of EpidemiologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Francesco Pignatti
- Oncology and Hematology OfficeEuropean Medicines AgencyAmsterdamThe Netherlands
| | - Jan J. Cornelissen
- Erasmus University Medical Center Cancer InstituteRotterdamThe Netherlands
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Sijs-Szabo A, Dinmohamed AG, Versluis J, van der Holt B, Bellido M, Hazenberg MD, van Gelder M, Schaap NPM, Meijer E, van der Wagen LE, Halkes CJM, Rijneveld AW, Cornelissen JJ. Allogeneic Stem Cell Transplantation in Patients >40 Years of Age With Acute Lymphoblastic Leukemia: Reduced Intensity Versus Myeloablative Conditioning. Transplantation 2023; 107:2561-2567. [PMID: 37389645 DOI: 10.1097/tp.0000000000004706] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2023]
Abstract
BACKGROUND The outcome in older patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory due to high relapse and nonrelapse mortality (NRM) rates. Allogeneic stem cell transplantation (alloHSCT) as postremission therapy has an important role in reducing relapse rate, albeit its application is limited in older adult patients due to alloHSCT-related morbidity and mortality. Reduced-intensity conditioning (RIC) alloHSCT has been developed as a less toxic conditioning regimen, but comparative studies with myeloablative conditioning (MAC) are limited in patients with ALL. METHODS In this retrospective study, RIC-alloHSCT (n = 111) was compared with MAC-alloHSCT (n = 77) in patients aged 41 to 65 y with ALL in first complete remission. MAC was predominantly applied by combining high-dose total body irradiation and cyclophosphamide, whereas RIC mainly consisted of fludarabine and 2 Gy total body irradiation. RESULTS Unadjusted overall survival was 54% (95% confidence interval [CI], 42%-65%) at 5 y in MAC recipients compared with 39% (95% CI, 29%-49%) in RIC recipients. Overall survival and relapse-free survival were not significantly associated with type of conditioning after adjusted for the covariates age, leukemia risk status at diagnosis, donor type, and donor and recipient gender combination. NRM was significantly lower after RIC (subdistribution hazard ratio: 0.41, 95% CI, 0.22-0.78; P = 0.006), whereas relapse was significantly higher (subdistribution hazard ratio: 3.04, 95% CI, 1.71-5.40; P < 0.001). CONCLUSIONS Collectively, RIC-alloHSCT has resulted in less NRM, but it was also found to be associated with a significantly higher relapse rate. These results suggest that MAC-alloHSCT may provide a more effective type of consolidation therapy for the reduction of relapse and that RIC-alloHSCT may be restricted to patients at higher risk for NRM.
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Affiliation(s)
- Aniko Sijs-Szabo
- Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands
- Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands
| | - Avinash G Dinmohamed
- Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
- Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jurjen Versluis
- Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands
| | - Bronno van der Holt
- Department of Hematology, HOVON Data Center, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands
| | - Mar Bellido
- Department of Hematology, Rijksuniversity Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Mette D Hazenberg
- Department of Hematology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Michel van Gelder
- Department of Hematology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Nicolaas P M Schaap
- Department of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, the Netherlands
| | - Ellen Meijer
- Department of Hematology, Amsterdam University Medical Center, Free University, Amsterdam, the Netherlands
| | | | | | - Anita W Rijneveld
- Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands
| | - Jan J Cornelissen
- Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands
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Modi D, Alkassis S, Kim S, Kin A, Deol A, Ayash L, Ratanatharathorn V, Uberti JP. Allogeneic stem cell transplant outcomes between TBI-containing reduced intensity and myeloablative conditioning regimens for ALL in complete remission. Leuk Lymphoma 2023; 64:1285-1294. [PMID: 37154379 DOI: 10.1080/10428194.2023.2206181] [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: 11/28/2022] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 05/10/2023]
Abstract
Total-body irradiation (TBI)-based conditioning regimen is preferred in acute lymphoblastic leukemia (ALL). We retrospectively evaluated allogeneic stem cell transplant (alloSCT) outcomes of 86 adult ALL patients in complete remission (CR) who received TBI-containing reduced intensity (RIC) (Flu/Mel/TBI = 31) and myeloablative conditioning (MAC) (VP16/TBI = 47; CY/TBI = 8) between January 2005 and December 2019. All patients received peripheral blood allografts. Patients in the RIC group were older than the MAC group (61 years old versus 36 years, p < .001). Donor was 8/8 HLA-matched in 83% and unrelated in 65% of patients. Three-year survival was 56.04% for RIC and 69.9% for MAC (HR 0.64; p = .19). Propensity score-based multivariable Cox analyses (PSCA) did not demonstrate any difference in grade III-IV acute graft versus host disease (GVHD) (SHR 1.23, p = .91), chronic GVHD (SHR 0.92, p = .88), survival (HR 0.94, p = .92), and relapse-free survival (HR 0.66, p = .47) between both groups, while relapse rate was lower (SHR 0.21, p = .02) for MAC compared to RIC. Our study did not demonstrate any difference in survival for TBI-containing RIC and MAC alloSCT for adult ALL in CR.
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Affiliation(s)
- Dipenkumar Modi
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Samer Alkassis
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Seongho Kim
- Biostatistics Core, Barbara Ann Karmanos Cancer Institute, Department of Oncology, Wayne State University, Detroit, MI, USA
| | - Andrew Kin
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Abhinav Deol
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Lois Ayash
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Voravit Ratanatharathorn
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Joseph P Uberti
- Department of Oncology, Blood & Marrow Stem Cell Transplant Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
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9
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Aureli A, Marziani B, Venditti A, Sconocchia T, Sconocchia G. Acute Lymphoblastic Leukemia Immunotherapy Treatment: Now, Next, and Beyond. Cancers (Basel) 2023; 15:3346. [PMID: 37444456 DOI: 10.3390/cancers15133346] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/14/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates, chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.
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Affiliation(s)
- Anna Aureli
- CNR Institute of Translational Pharmacology, Via Carducci 32, 67100 L'Aquila, Italy
| | - Beatrice Marziani
- Emergency Medicine Department, Sant'Anna University Hospital, Via A. Moro, 8, Cona, 44124 Ferrara, Italy
| | - Adriano Venditti
- Department of Biomedicine and Prevention, The University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Tommaso Sconocchia
- Division of Hematology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
| | - Giuseppe Sconocchia
- CNR Institute of Translational Pharmacology, Via Carducci 32, 67100 L'Aquila, Italy
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10
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Lv M, Liu L, He Y, Yang D, Ma Q, Pang A, Zhai W, Wei J, Huang Y, Chen X, Zhang G, Feng S, Han M, Jiang E, Zhang R. Outcomes of allogeneic or autologous stem cell transplantation followed by maintenance chemotherapy in adult patient with B-ALL in CR1 with no detectable minimal residual disease. Br J Haematol 2023. [PMID: 37157187 DOI: 10.1111/bjh.18846] [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: 11/21/2022] [Revised: 04/17/2023] [Accepted: 04/23/2023] [Indexed: 05/10/2023]
Abstract
Autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for B-cell acute lymphoblastic leukaemia (B-ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B-ALL in first complete remission who had received auto-HSCT or allogeneic HSCT (allo-HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto-HSCT demonstrated comparable 3-year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia-free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo-HSCT for patients with negative MRD, while the advantage of lower non-relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high-risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3-year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto-HSCT. However, no significant interaction was observed in the tests. In conclusion, auto-HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD-positive patients, allo-HSCT may be a more effective treatment.
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Affiliation(s)
- Mengnan Lv
- 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 & Peking Union Medical College, Tianjin, China
| | - Liangyi Liu
- 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 & Peking Union Medical College, Tianjin, China
| | - Yi He
- 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 & Peking Union Medical College, Tianjin, China
| | - Donglin Yang
- 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 & Peking Union Medical College, Tianjin, China
| | - Qiaoling Ma
- 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 & Peking Union Medical College, Tianjin, China
| | - Aiming Pang
- 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 & Peking Union Medical College, Tianjin, China
| | - Weihua Zhai
- 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 & Peking Union Medical College, Tianjin, China
| | - Jialin Wei
- 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 & Peking Union Medical College, Tianjin, China
| | - Yong Huang
- 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 & Peking Union Medical College, Tianjin, China
| | - Xin Chen
- 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 & Peking Union Medical College, Tianjin, China
| | - Guixin Zhang
- 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 & Peking Union Medical College, Tianjin, China
| | - Sizhou Feng
- 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 & Peking Union Medical College, Tianjin, China
| | - Mingzhe Han
- 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 & Peking Union Medical College, Tianjin, China
| | - Erlie Jiang
- 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 & Peking Union Medical College, Tianjin, China
| | - Rongli Zhang
- 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 & Peking Union Medical College, Tianjin, China
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11
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Pan Z, Wang L, Fu W, Jiang C, Zhang Z, Chen Q, Wang L, Hu X. Pediatric chemotherapy versus allo-HSCT for adolescent and adult Philadelphia chromosome-negative ALL in first complete remission: a meta-analysis. Ann Hematol 2023; 102:1131-1140. [PMID: 36947212 DOI: 10.1007/s00277-023-05160-2] [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: 12/26/2022] [Accepted: 03/04/2023] [Indexed: 03/23/2023]
Abstract
Pediatric-inspired chemotherapy significantly improves survival for adolescent and adult patients with acute lymphoblastic leukemia (ALL). However, the benefits over allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. To compare clinical outcomes between pediatric-inspired chemotherapy and allo-HSCT in consolidation therapy of adolescent and adult Philadelphia chromosome-negative (Ph-neg) ALL in first complete remission (CR1), related studies from MEDLINE, Embase, and Cochrane Controlled Register of Trials updated to July 2022 were searched. A total of 13 relevant trials including 3161 patients were included in the meta-analysis. Compared with allo-HSCT, pediatric-inspired chemotherapy achieved better OS (hazard risk (HR), 0.53; 95% confidence interval (CI), 0.41 to 0.68) and DFS (HR, 0.64; 95% CI, 0.48 to 0.86), with a significant reduction in NRM (risk ratio (RR), 0.30; 95% CI, 0.18 to 0.51), but no difference in the relapse rate (RR, 1.13; 95% CI, 0.93 to 1.39). When only studies based on intention-to-treat analysis were included, pediatric-inspired chemotherapy consistently conferred a survival advantage. In subgroup analyses, patients with baseline high-risk features demonstrated similar OS and DFS between pediatric-style chemotherapy and allo-HSCT, while pediatric-style chemotherapy had an OS and DFS advantage in standard-risk subgroup. Particularly, patients with positive minimal residual disease (MRD) achieved better OS and DFS if proceeded to allo-HSCT.
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Affiliation(s)
- Zengkai Pan
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Shanghai RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, China
| | - Luxiang Wang
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Shanghai RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, China
| | - Weijia Fu
- Department of Hematology, Institute of Hematology, Changhai Hospital, Changhai Road 168, Shanghai, 200433, China
| | - Chuanhe Jiang
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Shanghai RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, China
| | - Zilu Zhang
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Shanghai RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, China
| | - Qi Chen
- Department of Health Statistics, Naval Medical University, Xiangyin Road 800, Shanghai, 200433, China.
| | - Libing Wang
- Department of Hematology, Institute of Hematology, Changhai Hospital, Changhai Road 168, Shanghai, 200433, China.
| | - Xiaoxia Hu
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Shanghai RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Er Road 197, Shanghai, 200025, China.
- Collaborative Innovation Center of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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12
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Salman P, de Melo AC, Rico-Restrepo M, Rodriguez J, Russi A, Schmerling RA, Zambrano A, Cinat G. Addressing the unmet needs of patients with BRAF-mutated melanoma in Latin America: Expert perspective. Front Oncol 2023; 13:1032300. [PMID: 36998456 PMCID: PMC10043339 DOI: 10.3389/fonc.2023.1032300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 02/27/2023] [Indexed: 03/16/2023] Open
Abstract
Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF-status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF-mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma’s time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment.
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Affiliation(s)
- Pamela Salman
- Oncology Department, Oncovida Cancer Center, Santiago, Chile
- *Correspondence: Pamela Salman,
| | | | | | | | - Andrea Russi
- Departamento de Oncología, Hospital Universitario San Ignacio, Centro Javeriano de Oncología, Bogotá, Colombia
| | | | - Angela Zambrano
- Departamento de Oncología, Fundación Valle del Lili, Cali, Colombia
| | - Gabriela Cinat
- Instituto de Oncología Ángel Roffo, Universidad de Buenos Aires, Fundación CIDEA, Buenos Aires, Argentina
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13
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Aleshina OA, Galtseva IV, Kotova ES, Isinova GI, Obukhova TN, Dvirnik VN, Sudarikov AB, Grishunina ME, Samoilova OS, Kaplanov KD, Lapin VA, Bondarenko SN, Fokina ES, Minaeva NV, Konstantinova TS, Sveshnikova YV, Zinina EE, Antipova AS, Baranova OY, Borisenkova EA, Davydova YO, Kapranov NM, Kulikov SM, Chabaeva YA, Troitskaya VV, Parovichnikova EN. Treatment outcomes for acute T-lymphoblastic leukemias/lymphomas: data from the ALL-2016 multicenter prospective randomized trial. ONCOHEMATOLOGY 2023. [DOI: 10.17650/1818-8346-2023-18-1-20-30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Affiliation(s)
- O. A. Aleshina
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - I. V. Galtseva
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - E. S. Kotova
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - G. I. Isinova
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - T. N. Obukhova
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - V. N. Dvirnik
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - A. B. Sudarikov
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | | | | | - K. D. Kaplanov
- S.P. Botkin City Clinical Hospital, Moscow Healthcare Department
| | | | - S. N. Bondarenko
- I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia
| | - E. S. Fokina
- Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency
| | - N. V. Minaeva
- Kirov Research Institute of Hematology and Blood Transfusion, Federal Medical and Biological Agency
| | | | | | | | - A. S. Antipova
- N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
| | - O. Yu. Baranova
- N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
| | | | - Yu. O. Davydova
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - N. M. Kapranov
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - S. M. Kulikov
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - Yu. A. Chabaeva
- National Medical Research Center for Hematology, Ministry of Health of Russia
| | - V. V. Troitskaya
- National Medical Research Center for Hematology, Ministry of Health of Russia
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14
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Yafour N, Hamzy F, Elkababri M, Yakoub-Agha I, Bekadja MA. [Acute lymphoblastic leukemia in developing countries: Management from the transplant indication (allo/auto) until post-transplant follow-up. Guidelines from the SFGM-TC]. Bull Cancer 2023; 110:S30-S38. [PMID: 35562231 DOI: 10.1016/j.bulcan.2022.02.011] [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: 02/06/2022] [Revised: 02/16/2022] [Accepted: 02/18/2022] [Indexed: 11/26/2022]
Abstract
Management of acute lymphoblastic leukemia (ALL) patients in countries with limited resources depends on the means of prognostic stratification, available treatment and logistics. During the 12th annual harmonization workshops of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated working group reviewed the literature in order to elaborate unified guidelines for allogeneic hematopoietic cell transplantation (Allo-HCT) in this disease. Conventional poor prognostic factors can be used to determine the indication of allo-HCT in first remission. Patients lacking a HLA-matched related donor can be allografted with a haploidentical donor allo-HCT if available. Chemotherapy based conditioning regimen can be used if TBI is not available, because the probability to find a radiotherapy department with the capacity for total body irradiation is low. For patients with Philadelphia chromosome positive (Phi+) ALL, post-transplantation tyrosine kinase inhibitors as a systematic maintenance strategy is recommended. Autologous HCT is optional for Phi+ ALL patients with negative minimal residual disease, who not eligible for allo-HCT. Patients with refractory/relapsed disease have a poor prognosis which highlights the importance of acquiring in the future new therapies such as: blinatumumab, inotuzumab, and CAR-T cells.
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Affiliation(s)
- Nabil Yafour
- Université d'Oran 1, Ahmed-Ben-Bella, établissement hospitalier et universitaire 1(er) Novembre 1954, faculté de médecine, service d'hématologie et de thérapie cellulaire, BP 4166 Ibn-Rochd, 31000 Oran, Algérie.
| | - Faty Hamzy
- Hôpital Cheikh-Zaïd universitaire international, service d'hématologie et greffe, cité Al-Irfane-Hay Ryad avenue Allal-al-Fassi, 10000 Rabat, Maroc
| | - Maria Elkababri
- Hôpital d'enfants de Rabat, université Mohammed V de Rabat, service d'hématologie et oncologie pédiatrique, Rabat, Maroc
| | | | - Mohamed Amine Bekadja
- Université d'Oran 1, Ahmed-Ben-Bella, établissement hospitalier et universitaire 1(er) Novembre 1954, faculté de médecine, service d'hématologie et de thérapie cellulaire, BP 4166 Ibn-Rochd, 31000 Oran, Algérie
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15
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Autologous versus allogeneic hematopoietic cell transplantation for older patients with acute lymphoblastic leukemia. An analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2023; 58:393-400. [PMID: 36611097 DOI: 10.1038/s41409-022-01904-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 12/10/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023]
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is an option for elderly patients with acute lymphoblastic leukemia (ALL). We retrospectively compared results of RIC-allo-HCT from either a matched sibling donor (MSD, n = 209) or matched unrelated donor (MUD, n = 209) with autologous (auto, n = 142) HCT for patients aged 55 years or more treated in first complete remission (CR1) between 2000 and 2018. The probabilities of leukemia-free survival (LFS) at 5 years were 34% for RIC-allo-HCT versus 39% for auto-HCT (p = 0.11) while overall survival (OS) rates were 42% versus 45% (p = 0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 41% versus 51% (p = 0.22) and 25% versus 10% (p = 0.001), respectively. In a multivariate model, using auto-HCT as reference, the risk of NRM was increased for MSD-HCT (Hazard ratio [HR] = 2.1, p = 0.02) and MUD-HCT (HR = 3.08, p < 0.001), which for MUD-HCT translated into a decreased chance of LFS (HR = 1.55, p = 0.01) and OS (HR = 1.62, p = 0.008). No significant associations were found with respect to the risk of relapse. We conclude that for patients with ALL in CR1, aged above 55 years, auto-HCT may be considered a transplant option alternative to RIC-allo-HCT, although its value requires verification in prospective trials.
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16
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Li X, Zhu H, Sui T, Zhao X, Deng Q. A Case of Daratumumab-Induced Significant Decrease in Donor-Specific HLA Antibodies and Remission Induction Before Haploidentical Stem Cell Transplantation in a Refractory B-ALL Patient. Cell Transplant 2022; 31:9636897221132502. [PMID: 36278404 PMCID: PMC9597015 DOI: 10.1177/09636897221132502] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective: To explore the method of eliminating donor-specific anti-HLA antibodies (DSA)
in haploidentical stem cell transplantation (haplo-SCT). Methods: We present a refractory B-cell acute lymphoblastic leukemia (ALL) patient who
had strongly positive DSA, but had no human leukocyte antigen–matched donor.
Although CD38 expression on leukemia cells was negative, daratumumab
combined with etoposide and venetoclax therapy was chosen for her. Results: She achieved a significant decrease in DSA levels and complete remission on
the combination therapy with daratumumab. She then received a haplo-SCT from
a daughter as a donor and had a successful engraftment of donor stem cell.
In haplo-SCT, strongly positive DSA levels, directed against donor HLA
antigens, could be significantly reduced by daratumumab therapy before
transplantation and successfully bridge subsequent haplo-SCT. Conclusion: Although CD38 expression is negative in leukemia cells, refractory B-ALL
patients may still benefit from combination therapy with daratumumab. We
need further clinical observation.
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Affiliation(s)
- Xin Li
- Department of Hematology, Tianjin First
Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Haibo Zhu
- Department of Hematology, Tianjin First
Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Tao Sui
- Department of Hematology, Tianjin First
Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Xingli Zhao
- Departments of Oncology and Hematology,
Tianjin People’s Hospital, School of Medicine, Nankai University, Tianjin,
China
| | - Qi Deng
- Department of Hematology, Tianjin First
Central Hospital, School of Medicine, Nankai University, Tianjin, China,Qi Deng, Department of Hematology, Tianjin
First Central Hospital, School of Medicine, Nankai University, No. 24, Fukang
Road, Tianjin 300192, China.
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17
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Sun G, Tang B, Song K, Wu Y, Tu M, Wan X, Yao W, Geng L, Qiang P, Zhu X. Unrelated cord blood transplantation vs. HLA-matched sibling transplantation for adults with B-cell acute lymphoblastic leukemia in complete remission: superior OS for patients with long-term survival. STEM CELL RESEARCH & THERAPY 2022; 13:500. [PMID: 36210439 PMCID: PMC9549614 DOI: 10.1186/s13287-022-03186-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 09/30/2022] [Indexed: 12/03/2022]
Abstract
Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for adult acute lymphoblastic leukemia (ALL). For patients who lack a human leukocyte antigen (HLA)-matched sibling donor, unrelated cord blood (UCB) is an alternative graft option. Previous studies have focused mainly on all T- and B-cell ALL (B-ALL) patients, while data related specifically to adult B-ALL patients after UCB transplantation (UCBT) are scarce. Methods We retrospectively compared the outcomes of UCBT and HLA-matched sibling transplantation (MST) in the treatment of adult B-ALL patients in complete remission (CR) at our center. From June 2006 to December 2020, 156 adult B-ALL patients who achieved CR before transplantation were enrolled. The main clinical outcomes of UCBT and MST were analyzed. Results Hematopoietic recovery was significantly faster in MST recipients than in UCBT recipients. Higher incidences of grades II-IV and III-IV acute graft-versus host disease (aGVHD) were found in UCBT recipients (P < 0.001 and = 0.03), while a lower incidence of extensive chronic GVHD (cGVHD) was found in UCBT recipients (P < 0.001). The cumulative incidences of 2-year non-relapse mortality (NRM), 2-year relapse, 5-year disease-free survival (DFS) and 5-year GVHD-free relapse-free survival (GRFS) were comparable between MST and UCBT recipients. The overall survival (OS) during the first 700 days was similar between the MST and UCBT groups, while the OS of patients with a survival time of more than 700 days in the UCBT group was better than that in the MST group according to multivariate analysis (P = 0.03). Conclusions Our study shows that when treating adult B-ALL patients in CR, UCBT can achieve comparable effects as MST, may provide superior OS for patients with long-term survival, and should be considered a good alternative. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03186-3.
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18
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Künz T, Hauswirth AW, Hetzenauer G, Rudzki J, Nachbaur D, Steiner N. Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL). Cancers (Basel) 2022; 14:4290. [PMID: 36077822 PMCID: PMC9454969 DOI: 10.3390/cancers14174290] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/28/2022] [Accepted: 08/29/2022] [Indexed: 11/22/2022] Open
Abstract
Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy characterized by proliferation and accumulation of premature lymphoid blasts. Depending on risk factors, the survival of acute lymphoblastic leukemia has significantly improved over the last decades. During the last years, measurable residual disease (MRD) assessment has evolved into one of the most sensitive markers for prognosis and risk of relapse. For this reason, measurable residual disease detection and monitoring count as standard evaluation in patients with acute lymphoblastic leukemia. Allogeneic stem cell transplantation is still the recommended treatment option for patients with high and highest risk profiles as well as for relapsed or refractory settings. The increased understanding of the pathomechanism and heterogeneity of acute lymphoblastic leukemia has led to the development of several novel therapeutic opportunities such as tyrosine-kinase inhibitors, antibody-based therapies and CAR-T cells with the aim of improving clinical outcomes. Furthermore, the major advances in disease understanding of ALL have led to the identification of different subgroups and better disease stratification. Even though novel therapy targets are constantly developed, acute lymphoblastic leukemia remains a challenging and life-threatening disease. To improve the historically unsatisfying result in therapy of adult acute lymphoblastic leukemia many clinical trials have recently been initiated to determine the optimum combination regimens of novel and old agents for adult acute lymphoblastic leukemia.
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Affiliation(s)
- Tina Künz
- Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, A-6020 Innsbruck, Austria
| | - Alexander W. Hauswirth
- Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria
| | - Gabriele Hetzenauer
- Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, A-6020 Innsbruck, Austria
| | - Jakob Rudzki
- Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, A-6020 Innsbruck, Austria
| | - David Nachbaur
- Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, A-6020 Innsbruck, Austria
| | - Normann Steiner
- Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, A-6020 Innsbruck, Austria
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19
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Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Fusions Associated with Ph-like ALL. Blood Adv 2022; 6:4936-4948. [PMID: 35816633 PMCID: PMC9631622 DOI: 10.1182/bloodadvances.2022007597] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/01/2022] [Indexed: 11/20/2022] Open
Abstract
Posttransplant survival outcomes were comparable between adult patients with Ph-like ALL fusions and other high-risk B-cell ALL. In patients with Ph-like ALL, RFS was significantly influenced by disease status (P < .001) and conditioning regimen intensity (P = .014). Allogenic hematopoietic cell transplantation (alloHCT) is a well-established curative modality for acute lymphoblastic leukemia (ALL), yet large amounts of data describing alloHCT outcomes in Philadelphia (Ph)-like ALL are lacking. We retrospectively analyzed archived DNA samples from consecutive adults with B-cell Ph-negative ALL who underwent alloHCT in complete remission (CR) (n = 127) at our center between 2006 and 2020. Identification of fusions associated with Ph-like ALL was performed using cumulative results from RNA-seq, conventional cytogenetics, fluorescence in situ hybridization, and whole genome array studies. Fusions associated with Ph-like ALL were detected in 56 (44%) patients, of whom 38 were carrying CRLF2r. Compared with other non–Ph-like ALL (n = 71), patients with fusions associated with Ph-like ALL were more frequently Hispanic (P = .008), were less likely to carry high-risk cytogenetics (P < .001), and were more likely to receive blinatumomab prior to HCT (P = .019). With the median followup of 3.5 years, patients with Ph-like ALL fusions had comparable posttransplant outcomes compared with other B-cell ALL: 3-year relapse-free survival (RFS) (41% vs 44%; P = .36), overall survival (OS) (51% vs 50%; P = .59), and relapse (37% vs 31%; P = .47). In multivariable analysis, age (P = .023), disease status at the time of transplant (P < .001), and donor type (P = .015) influenced OS. RFS (primary endpoint) was significantly influenced by disease status (P < .001) and conditioning regimen intensity (P = .014). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.
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20
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Brown PA, Shah B, Advani A, Aoun P, Boyer MW, Burke PW, DeAngelo DJ, Dinner S, Fathi AT, Gauthier J, Jain N, Kirby S, Liedtke M, Litzow M, Logan A, Luger S, Maness LJ, Massaro S, Mattison RJ, May W, Oluwole O, Park J, Przespolewski A, Rangaraju S, Rubnitz JE, Uy GL, Vusirikala M, Wieduwilt M, Lynn B, Berardi RA, Freedman-Cass DA, Campbell M. Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:1079-1109. [PMID: 34551384 DOI: 10.6004/jnccn.2021.0042] [Citation(s) in RCA: 139] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.
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Affiliation(s)
- Patrick A Brown
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | - Anjali Advani
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | | | - Shira Dinner
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - Jordan Gauthier
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | - Nitin Jain
- The University of Texas MD Anderson Cancer Center
| | | | | | | | - Aaron Logan
- UCSF Helen Diller Family Comprehensive Cancer Center
| | - Selina Luger
- Abramson Cancer Center at the University of Pennsylvania
| | | | | | | | | | | | - Jae Park
- Memorial Sloan Kettering Cancer Center
| | | | | | - Jeffrey E Rubnitz
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | - Geoffrey L Uy
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - Beth Lynn
- National Comprehensive Cancer Network
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21
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Optimal treatment for Philadelphia-negative acute lymphoblastic leukemia in first remission in the era of high-intensity chemotherapy. Int J Hematol 2021; 114:608-619. [PMID: 34328634 DOI: 10.1007/s12185-021-03198-4] [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: 06/11/2021] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 10/20/2022]
Abstract
The optimal treatment for Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) has not been established in the high-intensity chemotherapy era. The outcomes of patients with Ph-negative ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched related or unrelated donor in CR1 (HSCT-MRD group and HSCT-MUD group) were obtained from a Japanese registry database. Patients aged 16-24 years and 25-65 years were analyzed separately, and their outcomes were compared to those of patients who continued high-intensity chemotherapy in CR1 in studies (202U group and 202O group) by the Japan Adult Leukemia Study Group (JALSG). In the HSCT-MRD group, patients younger than 25 years had lower overall survival (OS) than the 202U group, presumably due to the higher non-relapse mortality (NRM) in the HSCT-MRD group. Patients 25 years and older had similar OS to the 202O group. The lower relapse rate was counterbalanced by higher NRM in the HSCT-MRD group. In the HSCT-MUD group, patients in both age groups had similar OS to their corresponding groups in the JALSG studies. In conclusion, high-intensity chemotherapy may change the role of HSCT for Ph-negative ALL.
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22
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Arslan S, Pullarkat V, Aldoss I. Indications for Allogeneic HCT in Adults with Acute Lymphoblastic Leukemia in First Complete Remission. Curr Treat Options Oncol 2021; 22:63. [PMID: 34097131 DOI: 10.1007/s11864-021-00860-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 01/12/2023]
Abstract
OPINION STATEMENT Acute lymphoblastic leukemia (ALL) in adults is associated with poor outcomes as compared to children when treated with chemotherapy, leading to a considerably inferior cure rate. Historically, consolidation with allogeneic hematopoietic cell transplant (alloHCT) was routinely recommended for eligible adults with ALL in first complete remission (CR1) if a donor was available, since randomized studies showed superiority over continuing chemotherapy. With the increasing use of pediatric-inspired frontline regimens in young adults with ALL and the availability of novel salvage agents for relapsed/refractory B-cell ALL that have high potential in inducing a second CR, the role of early alloHCT in the treatment paradigm for ALL needs to be reevaluated, and the decision should be individualized for each patient. Simultaneously, alloHCT has evolved considerably lately, and historical randomized studies that have proven the benefit of alloHCT in adults with ALL in CR1 did not included the increasing use of reduced intensity conditioning and haploidentical transplants, and therefore, data may not entirely apply. Nowadays, detectable minimal residual disease (MRD) is the most prognostic determinant of ALL outcome and should be a major consideration in the decision to perform alloHcT in CR1. Nonetheless, other biological and clinical factors remain relevant and can support the complex decision-making. Such factors include high-risk leukemia genetics, the type of administered chemotherapy regimen and the ability of the patient to tolerate all key components of the regimen, and the availability of effective salvage therapies that allow alloHCT to be performed in CR2 in case of relapse after chemotherapy.
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Affiliation(s)
- Shukaib Arslan
- Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA
| | - Vinod Pullarkat
- Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA
| | - Ibrahim Aldoss
- Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
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23
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Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation. Blood Adv 2021; 4:2073-2083. [PMID: 32396617 DOI: 10.1182/bloodadvances.2020001499] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 04/02/2020] [Indexed: 01/03/2023] Open
Abstract
We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.
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24
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Early autologous and allogeneic peripheral blood stem cell transplantation for adult patients with acute B and T cell precursor neoplasms: a 12-year single center experience. Ann Hematol 2021; 100:809-816. [PMID: 33496839 PMCID: PMC7914178 DOI: 10.1007/s00277-020-04391-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 12/21/2020] [Indexed: 12/25/2022]
Abstract
Adult acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a rare and heterogeneous malignancy characterized by uncontrolled proliferation of B or T cell precursor cells. Here, we retrospectively analyzed the outcome of early autologous stem cell transplantation in standard-risk patients in first complete remission (n=24) and of allogeneic transplantation in high and highest risk, and relapsed/refractory patients (n=35). The 10-year overall survival after autologous transplantation was 45%. The 10-year overall survival after allogeneic transplantation was 58%. The cumulative incidence of relapse was 29% after allogeneic and 67% after autologous transplantation. The cumulative incidence of non-relapse mortality was 0% after autologous and 12% after allogeneic transplantation. This retrospective single center analysis in a limited number of standard-risk patients clearly demonstrates that early autologous transplantation in first complete remission leads to an acceptable long-term outcome with a short overall treatment duration of less than 6 months compared with more than 2 years with conventional chemotherapy. More sensitive and standardized methods to detect minimal residual disease (MRD) will further help to identify those patients more accurately who are most likely to benefit from such a short and intensive treatment strategy (i.e., MRD negative standard-risk patients) or those who require early targeted therapy (e.g., blinatumomab) in case of MRD positivity. Early allogeneic transplantation results in long-term survival/cure in nearly two-thirds of all high and highest risk, and relapsed/refractory patients.
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25
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Greil C, Engelhardt M, Ihorst G, Duque-Afonso J, Shoumariyeh K, Bertz H, Marks R, Zeiser R, Duyster J, Finke J, Wäsch R. Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia. Bone Marrow Transplant 2020; 56:841-852. [PMID: 33130821 PMCID: PMC8266681 DOI: 10.1038/s41409-020-01101-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 09/23/2020] [Accepted: 10/20/2020] [Indexed: 02/07/2023]
Abstract
Allogeneic stem cell transplantation (allo-SCT) offers a curative option in adult patients with acute lymphoblastic leukemia (ALL). Prognostic factors for survival after allo-SCT have not been sufficiently defined: pheno-/genotype, patients´ age, conditioning regimens and remission at allo-SCT are under discussion. We analyzed the outcome of 180 consecutive adult ALL-patients undergoing allo-SCT at our center between 1995 and 2018 to identify specific prognostic factors. In our cohort 19% were older than 55 years, 28% had Philadelphia-positive B-ALL, 24% T-ALL. 54% were transplanted in first complete remission (CR1), 13% in CR2 after salvage therapy, 31% reached no remission (8% within first-line, 23% within salvage therapy). In 66% conditioning contained total body irradiation (TBI). With a median follow-up of 10 years, we observed an overall survival of 33% at 10 years, and a progression free survival of 31%. The cumulative incidence of relapse was 41% at 10 years, the cumulative incidence of non-relapse mortality 28%. Acute graft-versus-host disease (GvHD) II°-IV° occurred in 31%, moderate/severe chronic GvHD in 27%. Survival was better in patients reaching CR before allo-SCT and in those receiving TBI. No difference between patients younger/older than 55 years and between different phenotypes was observed. Survival after allo-SCT improved considerably over the last decades.
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Affiliation(s)
- C Greil
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - M Engelhardt
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - G Ihorst
- Clinical Trials Unit, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - J Duque-Afonso
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - K Shoumariyeh
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - H Bertz
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - R Marks
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - R Zeiser
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - J Duyster
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - J Finke
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany.,Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - R Wäsch
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany. .,Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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26
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Role of Allogeneic HCT as Postremission Therapy for Transplant-Eligible Adult Lymphoblastic Leukemia/Lymphoma After Frontline Hyper-CVAD. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2020; 20:690-696. [PMID: 32636149 DOI: 10.1016/j.clml.2020.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/13/2020] [Accepted: 05/14/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with cytarabine and methotrexate (hyper-CVAD) is a commonly used regimen in adults with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Adult patients fit for pediatric-inspired protocols have an excellent outcome with chemotherapy alone. However, it is unclear whether patients receiving hyper-CVAD should undergo allogeneic hematopoietic cell transplantation (HCT) as postremission therapy. Our aim was to examine the role of HCT at first complete remission (CR1) in adult ALL/LBL after hyper-CVAD. PATIENTS AND METHODS Adult patients with newly diagnosed ALL/LBL receiving frontline hyper-CVAD from 2008 to 2018 were identified and records retrospectively extracted. RESULTS A total of 85 patients were identified and included for further analysis. The median (range) age was 23 (14-68) years, and 56 (66%) were male. A total of 24 (28%) had adverse cytogenetics, and 48 (56%) had at least one risk factor. All patients received hyper-CVAD as induction; induction failure was seen in 10 (12%). A total of 38 patients continued the hyper-CVAD course, while the remaining 47 received HCT in CR1. Three-year event-free survival (EFS) and overall survival for the entire cohort were 51.4% and 61.6%, respectively. Median follow-up of alive patients was 39.9 (3.8-123.8) months. At multivariable analysis for EFS, induction failure was associated with worse outcome (hazard ratio [HR], 4.8; 95% confidence interval [CI] 1.7-13.7; P = .003), whereas HCT in CR1 improved outcome (HR, 0.42; 95% CI 0.18-0.97; P = .044). Furthermore, HCT in CR1 was the only prognostic factor for overall survival (HR, 0.3; 95% CI 0.11-0.85; P = .023). CONCLUSION HCT at CR1 resulted in a favorable EFS and overall survival in ALL/LBL patients after hyper-CVAD frontline therapy. Given that hyper-CVAD is a widely used protocol for adult patients, further examination of this observation is warranted.
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Lv M, Jiang Q, Zhou DB, Hu Y, Liu DH, Wu DP, Wang JB, Jiang H, Wang J, Chang YJ, Wang Y, Zhang XH, Xu LP, Liu KY, Huang XJ. Comparison of haplo-SCT and chemotherapy for young adults with standard-risk Ph-negative acute lymphoblastic leukemia in CR1. J Hematol Oncol 2020; 13:52. [PMID: 32414392 PMCID: PMC7227076 DOI: 10.1186/s13045-020-00879-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 04/23/2020] [Indexed: 12/02/2022] Open
Abstract
Abstract Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18–39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen (n = 55) or haplo-SCT (n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8–93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk factor for the CIR (HR 0.195, 95% CI 0.076–0.499, P = 0.001), LFS (HR 0.297, 95% CI 0.131–0.675, P = 0.003), and OS (HR 0.346, 95% CI 0.140–0.853, P = 0.011). In all subgroups, CIR was lower in haplo-SCT. Myeloablative haplo-SCT with ATG+G-CSF might be one of the preferred therapies for YA patients with standard-risk Ph-ALL. Trial registration ClinicalTrials.gov. Registered on 23 January 2014, https://clinicaltrials.gov/ct2/show/NCT02042690
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Affiliation(s)
- Meng Lv
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Qian Jiang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Dao-Bin Zhou
- Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Hu
- Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dai-Hong Liu
- General Hospital of PLA (People's Liberation Army of China), Beijing, China
| | - De-Pei Wu
- The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Disease, Suzhou, China
| | - Jing-Bo Wang
- Peking University Aerospace Center Hospital, Beijing, China
| | - Hao Jiang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Jing Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Ying-Jun Chang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiao-Hui Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Lan-Ping Xu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Kai-Yan Liu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China
| | - Xiao-Jun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China. .,Peking-Tsinghua Center for Life Sciences, Beijing, China. .,Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies (2019RU029), Chinese Academy of Medical Sciences, Beijing, China.
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Biernacki MA, Sheth VS, Bleakley M. T cell optimization for graft-versus-leukemia responses. JCI Insight 2020; 5:134939. [PMID: 32376800 DOI: 10.1172/jci.insight.134939] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Protection from relapse after allogeneic hematopoietic cell transplantation (HCT) is partly due to donor T cell-mediated graft-versus-leukemia (GVL) immune responses. Relapse remains common in HCT recipients, but strategies to augment GVL could significantly improve outcomes after HCT. Donor T cells with αβ T cell receptors (TCRs) mediate GVL through recognition of minor histocompatibility antigens and alloantigens in HLA-matched and -mismatched HCT, respectively. αβ T cells specific for other leukemia-associated antigens, including nonpolymorphic antigens and neoantigens, may also deliver an antileukemic effect. γδ T cells may contribute to GVL, although their biology and specificity are less well understood. Vaccination or adoptive transfer of donor-derived T cells with natural or transgenic receptors are strategies with potential to selectively enhance αβ and γδ T cell GVL effects.
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Affiliation(s)
- Melinda A Biernacki
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.,Department of Medicine, and
| | - Vipul S Sheth
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Marie Bleakley
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.,Department of Pediatrics, University of Washington, Seattle, Washington, USA
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29
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El Fakih R, Savani B, Mohty M, Aljurf M. Hematopoietic Cell Transplant Consideration for Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia Patients. Biol Blood Marrow Transplant 2020; 26:e16-e20. [DOI: 10.1016/j.bbmt.2019.08.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 08/10/2019] [Accepted: 08/14/2019] [Indexed: 01/06/2023]
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Summers C, Sheth VS, Bleakley M. Minor Histocompatibility Antigen-Specific T Cells. Front Pediatr 2020; 8:284. [PMID: 32582592 PMCID: PMC7283489 DOI: 10.3389/fped.2020.00284] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 05/06/2020] [Indexed: 01/05/2023] Open
Abstract
Minor Histocompatibility (H) antigens are major histocompatibility complex (MHC)/Human Leukocyte Antigen (HLA)-bound peptides that differ between allogeneic hematopoietic stem cell transplantation (HCT) recipients and their donors as a result of genetic polymorphisms. Some minor H antigens can be used as therapeutic T cell targets to augment the graft-vs.-leukemia (GVL) effect in order to prevent or manage leukemia relapse after HCT. Graft engineering and post-HCT immunotherapies are being developed to optimize delivery of T cells specific for selected minor H antigens. These strategies have the potential to reduce relapse risk and thereby permit implementation of HCT approaches that are associated with less toxicity and fewer late effects, which is particularly important in the growing and developing pediatric patient. Most minor H antigens are expressed ubiquitously, including on epithelial tissues, and can be recognized by donor T cells following HCT, leading to graft-vs.-host disease (GVHD) as well as GVL. However, those minor H antigens that are expressed predominantly on hematopoietic cells can be targeted for selective GVL. Once full donor hematopoietic chimerism is achieved after HCT, hematopoietic-restricted minor H antigens are present only on residual recipient malignant hematopoietic cells, and these minor H antigens serve as tumor-specific antigens for donor T cells. Minor H antigen-specific T cells that are delivered as part of the donor hematopoietic stem cell graft at the time of HCT contribute to relapse prevention. However, in some cases the minor H antigen-specific T cells delivered with the graft may be quantitatively insufficient or become functionally impaired over time, leading to leukemia relapse. Following HCT, adoptive T cell immunotherapy can be used to treat or prevent relapse by delivering large numbers of donor T cells targeting hematopoietic-restricted minor H antigens. In this review, we discuss minor H antigens as T cell targets for augmenting the GVL effect in engineered HCT grafts and for post-HCT immunotherapy. We will highlight the importance of these developments for pediatric HCT.
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Affiliation(s)
- Corinne Summers
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.,Department of Pediatrics, University of Washington, Seattle, WA, United States
| | - Vipul S Sheth
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
| | - Marie Bleakley
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.,Department of Pediatrics, University of Washington, Seattle, WA, United States
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31
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Li Y, Guo R, Wang L, Li S, Zhu Z, Tu P. G-CSF administration results in thrombocytopenia by inhibiting the differentiation of hematopoietic progenitors into megakaryocytes. Biochem Pharmacol 2019; 169:113624. [DOI: 10.1016/j.bcp.2019.113624] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 08/27/2019] [Indexed: 12/21/2022]
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32
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Parovichnikova E, Troitskaya V, Sokolov A, Gavrilina O, Akhmerzaeva Z, Kuzmina L, Kliasova G, Chabaeva J, Kulikov S, Bondarenko S, Baranova O, Samoilova O, Kaplanov K, Minaeva N, Savchenko V. Can Less Intensive Chemotherapy and an Autotransplant Cure Adult T-Cell Acute Lymphoblastic Leukemia? Acta Haematol 2019; 143:131-139. [PMID: 31597157 DOI: 10.1159/000502435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 07/30/2019] [Indexed: 11/19/2022]
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a rare disease usually treated with intensive, high-dose consolidation chemotherapy followed by an allotransplant in a substantial number of patients. The data of the RALL-2009 study on 125 adult T-ALL patients suggest that similar total chemotherapy doses given less intensively over a longer interval without interruptions and with an auto- rather than an allotransplant produce outcomes like current more intensive protocols and an allotransplant: 9-year cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and survival were 24% (95% CI 16-33%), 70% (95% CI 59-79%) and 62% (95% CI 51-72%). In a landmark analysis, subjects achieving a complete remission and receiving an autotransplant had a lower 9-year CIR (9% [95% CI 2-22%] vs. 29% [95% CI 16-43%]; p = 0.0076) and better LFS (91% [95% CI 79-98%] vs. 58% [95% CI 41-74%]; p = 0.0009) and survival (92% [95% CI 77-99%] vs. 60% [95% CI 44-77%]; p = 0.001) compared with subjects not receiving an autotransplant. In a multivariate analysis, white blood cells ≥100 × 109/L at study entry were significantly associated with worse LFS (HR = 2.842 [95% CI 1.131-7.143]; p = 0.0263) and survival (HR = 6.085 [95% CI 1.918-19.3]; p = 0.0022) because of more early deaths (HR = 2.42 [95% CI 1.04-5.67]; p = 0.041). Receiving an autotransplant correlated with a lower CIR (HR = 0.23 [95% CI 0.07-0.73]; p = 0.0136) and better LFS (HR = 0.27 [95% CI 0.08-0.85]; p = 0.0256) and survival (HR = 0.158 [95% CI 0.045-0.550]; p = 0.0037).
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Affiliation(s)
- Elena Parovichnikova
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation,
| | - Vera Troitskaya
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Andrey Sokolov
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Olga Gavrilina
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Zalina Akhmerzaeva
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Larissa Kuzmina
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Galina Kliasova
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Julia Chabaeva
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Sergey Kulikov
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
| | - Sergey Bondarenko
- Clinical Research Institution of Pediatric Hematology and Transplantation under the Name of Raisa Gorbacheva, State Medical University, St. Petersburg, Russian Federation
| | - Olga Baranova
- National Oncology Research Center of the Russian Ministry of Health, Moscow, Russian Federation
| | - Olga Samoilova
- Hematology Department, Regional Clinical Hospital, Nijniy Novgorod, Russian Federation
| | | | - Natalia Minaeva
- Kirov Research Institute of Hematology and Blood Transfusion under the Federal Medical Biological Agency, Kirov, Russian Federation
| | - Valeriy Savchenko
- National Research Center for Hematology of the Russian Ministry of Health, Moscow, Russian Federation
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DeFilipp Z, Advani AS, Bachanova V, Cassaday RD, Deangelo DJ, Kebriaei P, Rowe JM, Seftel MD, Stock W, Tallman MS, Fanning S, Inamoto Y, Kansagra A, Johnston L, Nagler A, Sauter CS, Savani BN, Perales MA, Carpenter PA, Larson RA, Weisdorf D. Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant 2019; 25:2113-2123. [PMID: 31446198 DOI: 10.1016/j.bbmt.2019.08.014] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 08/16/2019] [Indexed: 01/05/2023]
Abstract
The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.
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Affiliation(s)
- Zachariah DeFilipp
- Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA.
| | - Anjali S Advani
- Department of Medical Oncology & Hematology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
| | - Veronika Bachanova
- Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN
| | - Ryan D Cassaday
- Division of Clinical Research, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, WA, USA
| | - Daniel J Deangelo
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Partow Kebriaei
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jacob M Rowe
- Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel
| | | | - Wendy Stock
- Department of Hematology and Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL
| | - Martin S Tallman
- Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY
| | - Suzanne Fanning
- Hematology and Medical Oncology, Greenville Health System Cancer Institute, Greenville, SC
| | - Yoshihiro Inamoto
- Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Ankit Kansagra
- Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX
| | - Laura Johnston
- Department of Medicine, Stanford University Medical Center, Stanford, CA
| | - Arnon Nagler
- Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Craig S Sauter
- Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY
| | - Bipin N Savani
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Miguel-Angel Perales
- Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY
| | - Paul A Carpenter
- Division of Clinical Research, Fred Hutchinson Cancer Research Center and Department of Pediatrics, University of Washington, Seattle, WA, USA
| | - Richard A Larson
- Department of Hematology and Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL
| | - Daniel Weisdorf
- Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN
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Approach to the Adult Acute Lymphoblastic Leukemia Patient. J Clin Med 2019; 8:jcm8081175. [PMID: 31390838 PMCID: PMC6722778 DOI: 10.3390/jcm8081175] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/29/2019] [Accepted: 08/01/2019] [Indexed: 02/06/2023] Open
Abstract
During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.
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35
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Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia. Med Clin (Barc) 2019; 153:28-34. [PMID: 30857792 DOI: 10.1016/j.medcli.2019.01.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 01/07/2019] [Accepted: 01/09/2019] [Indexed: 11/23/2022]
Abstract
Immunotherapy is changing the treatment of acute lymphoblastic leukaemia (ALL) in adults and children. However, regardless of these new therapies, allogeneic hematopoietic cell transplantation (allo-HCT) still play a key role in the treatment of ALL, although it is uncertain how these new therapies will impact on the transplant procedure and indications. This article reviews the indications of allo-HCT for children and adults diagnosed with ALL, the different sources and conditioning regimens for transplantation as well as the role of measurable residual diseases pre- and post-HCT in the era of the new therapies for ALL.
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Giebel S, Marks DI, Boissel N, Baron F, Chiaretti S, Ciceri F, Cornelissen JJ, Doubek M, Esteve J, Fielding A, Foa R, Gorin NC, Gökbuget N, Hallböök H, Hoelzer D, Paravichnikova E, Ribera JM, Savani B, Rijneveld AW, Schmid C, Wartiovaara-Kautto U, Mohty M, Nagler A, Dombret H. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2019; 54:798-809. [PMID: 30385870 DOI: 10.1038/s41409-018-0373-4] [Citation(s) in RCA: 97] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 10/08/2018] [Accepted: 10/10/2018] [Indexed: 12/24/2022]
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is a standard of care for adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) and high risk of relapse. However, the stratification systems vary among study groups. Inadequate response at the level of minimal residual disease is the most commonly accepted factor indicating the need for alloHSCT. In this consensus paper on behalf of the European Working Group for Adult Acute Lymphoblastic Leukemia and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize available evidence and reflect current clinical practice in major European study groups regarding both indications for HSCT and particular aspects of the procedure including the choice of donor, source of stem cells and conditioning. Finally, we propose recommendations for daily clinical practice as well as for planning of prospective trials.
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Affiliation(s)
- Sebastian Giebel
- Maria Sklodowska-Curie Institute-Cancer Center, Gliwice Branch, Gliwice, Poland.
| | - David I Marks
- University Hospitals Bristol National Health Service Foundation Trust, Bristol, UK
| | | | | | | | | | - Jan J Cornelissen
- Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | | | | | - Adele Fielding
- North London Cancer Network, Univ. College London Hosp, London, UK
| | | | - Norbert-Claude Gorin
- EBMT Acute Leukemia Working Party Office, Paris, France
- Hospital Saint-Antoine, Paris, France
| | - Nicola Gökbuget
- Maria Sklodowska-Curie Institute-Cancer Center, Gliwice Branch, Gliwice, Poland
- Hopital St. Louis, Paris, France
| | | | - Dieter Hoelzer
- University Hospital, Goethe University, Frankfurt, Germany
| | - Elena Paravichnikova
- FGBU Hematology Research Center, Russia Federation Ministry of Public Health, Moscow, Russia
| | - Josep-Maria Ribera
- ICO-Hospital Germans Trias I Pujol, Jose Carreras Research Institute, Badalona, Spain
| | - Bipin Savani
- Vanderbilt University Medical Center, Nashville, USA
| | - Anita W Rijneveld
- Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Christoph Schmid
- Klinikum Augsburg, Ludwig-Maximilians-Universitaet, Munich-Augsburg, Germany
| | | | - Mohamad Mohty
- North London Cancer Network, Univ. College London Hosp, London, UK
- EBMT Acute Leukemia Working Party Office, Paris, France
| | - Arnon Nagler
- North London Cancer Network, Univ. College London Hosp, London, UK
- Chaim Sheba Medical Center, Tel-Hashomer, Israel
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Damlaj M, Snnallah M, Alhejazi A, Ghazi S, Alahmari B, Alaskar A, Al-Zahrani M. Graft vs host disease impacts overall survival post allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia/lymphoma. World J Transplant 2018; 8:252-261. [PMID: 30596032 PMCID: PMC6304336 DOI: 10.5500/wjt.v8.i7.252] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 09/07/2018] [Accepted: 11/03/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma (ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation (HCT) at our center during the period of 2010-2017
METHODS After due institutional review board approval, patients with high risk ALL/LBL post HCT were identified and included. All records were retrospectively collected. Time to event analysis was calculated from the date of HCT until event of interest or last follow up with Kaplan-Meir means. Cox regression model was used for multivariable analysis calculation.
RESULTS A total of 69 patients were enrolled and examined with a median age of 21 (14-61). After a median follow up of 15 mo (2-87.3), the 2-year cumulative incidence of relapse, cumulative incidence of non-relapse mortality, progression free survival and overall survival (OS) were 34.1%, 10.9%, 54.9% and 62.8%, respectively. In a multivariable analysis for OS; acute graft vs host disease (GVHD) and chronic GVHD were significant with corresponding hazard ratio 4.9 (1.99-12; P = 0.0007) and 0.29 (0.1-0.67; P = 0.0044), respectively.
CONCLUSION Allogeneic-HCT for high risk ALL/LBL resulted in promising remissions particularly for patients with cGVHD.
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Affiliation(s)
- Moussab Damlaj
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
| | - Mohammad Snnallah
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
| | - Ayman Alhejazi
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
| | - Samer Ghazi
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
| | - Bader Alahmari
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
| | - Ahmed Alaskar
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
| | - Mohsen Al-Zahrani
- Division of Hematology and HCT, Department of Oncology, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
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38
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Damlaj M, Snnallah M, Alhejazi A, Ghazi S, Alahmari B, Alaskar A, Al-Zahrani M. Graft vs host disease impacts overall survival post allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia/lymphoma. World J Transplant 2018. [DOI: 10.5500/wjt.v8.i7.000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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39
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Aldoss I, Pullarkat V. Indications for allogeneic hematopoietic cell transplantation for adults with Philadelphia-chromosome negative acute lymphoblastic leukemia in first complete remission: all about MRD? Bone Marrow Transplant 2018; 54:3-5. [DOI: 10.1038/s41409-018-0398-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Accepted: 10/31/2018] [Indexed: 12/25/2022]
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40
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Kotb A, El Fakih R, Hanbali A, Hawsawi Y, Alfraih F, Hashmi S, Aljurf M. Philadelphia-like acute lymphoblastic leukemia: diagnostic dilemma and management perspectives. Exp Hematol 2018; 67:1-9. [PMID: 30075295 DOI: 10.1016/j.exphem.2018.07.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 07/22/2018] [Accepted: 07/24/2018] [Indexed: 01/02/2023]
Abstract
Acute lymphoblastic leukemia (ALL) is an aggressive hematologic malignancy characterized by suboptimal outcomes in the adult age group. Recently, a new subtype called Philadelphia (Ph)-like ALL has been described. This subgroup is characterized by high cytokine receptor and tyrosine kinase signaling expression, resulting in kinase activation through stimulation of two main pathways, the ABL and JAK/STAT pathways. The diagnostic method or approach for Ph-like ALL is still not standardized and efforts are ongoing to identify an easy and applicable diagnostic method. Accurate and standard testing approaches are much needed and this will facilitate better understanding of this subgroup, including better estimation of the prevalence and incidence in different age groups and the clinical outcomes of such new entity. Here, we review the currently available diagnostic tools, activated pathways, and different therapeutic approaches used to target this subgroup.
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Affiliation(s)
- Ahmed Kotb
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Riad El Fakih
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.
| | - Amr Hanbali
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Yousef Hawsawi
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Feras Alfraih
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Shahrukh Hashmi
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Mahmoud Aljurf
- King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
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41
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Luskin MR, DeAngelo DJ. Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Curr Hematol Malig Rep 2018; 12:370-379. [PMID: 28656487 DOI: 10.1007/s11899-017-0394-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance. Several anti-CD19 CAR T cell constructs have induced high response rates in heavily pre-treated populations, although durability of response varied. Severe toxicity (cytokine release syndrome and neurotoxicity) is the primary constraint to broad implementation of CAR T cell therapy. Here, we review the experience of CAR T cell therapy for ALL and ongoing efforts to modify existing technology to improve efficacy and decrease toxicity. As an anti-CD19 CAR T cell construct may be FDA approved soon, we focus on issues relevant to practicing clinicians.
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MESH Headings
- Antigens, CD19/genetics
- Antigens, CD19/immunology
- Antigens, CD19/metabolism
- Humans
- Immunotherapy, Adoptive/methods
- Neoplasm Recurrence, Local
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy
- Receptors, Antigen, T-Cell/genetics
- Receptors, Antigen, T-Cell/immunology
- Receptors, Antigen, T-Cell/metabolism
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/immunology
- Recombinant Fusion Proteins/metabolism
- T-Lymphocytes/immunology
- T-Lymphocytes/metabolism
- T-Lymphocytes/transplantation
- Treatment Outcome
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Affiliation(s)
- Marlise R Luskin
- Harvard Medical School, Boston, MA, USA.
- Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
| | - Daniel J DeAngelo
- Harvard Medical School, Boston, MA, USA
- Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA
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Hematopoietic Stem Cell Transplantation for Adult Philadelphia-Negative Acute Lymphoblastic Leukemia in the First Complete Remission in the Era of Minimal Residual Disease. Curr Oncol Rep 2018; 20:36. [PMID: 29577208 DOI: 10.1007/s11912-018-0679-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
PURPOSE OF REVIEW The purpose of this review is to discuss the potential role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia-negative (Ph-) adult acute lymphoblastic leukemia (ALL) in first complete remission (CR1) in the era of minimal residual disease (MRD). RECENT FINDINGS Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT. In addition, MRD status both pre- and post-HSCT has been found to correlate directly with the risk of relapse. Currently, the clinical challenge consists on applying MRD and molecular failure to integrate novel agents and immunotherapy to lower MRD before allo-HSCT and to modulate the graft versus leukemia (GVL) effect after transplant.
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Dinner S, Gurbuxani S, Jain N, Stock W. Acute Lymphoblastic Leukemia in Adults. Hematology 2018. [DOI: 10.1016/b978-0-323-35762-3.00066-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation. Biol Blood Marrow Transplant 2017; 24:945-955. [PMID: 29275139 DOI: 10.1016/j.bbmt.2017.12.784] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 12/13/2017] [Indexed: 11/24/2022]
Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is curative for patients with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR1) with chemotherapy. However, the benefit of consolidation chemotherapy remains uncertain in patients undergoing alloHCT. We compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 (n = 109), 1 (n = 93), or 0 cycles (n = 322) of consolidation before myeloablative alloHCT from 2008 to 2012. As expected, time to alloHCT was longer with increasing cycles of consolidation. Patients receiving ≥2, 1, or 0 cycles of consolidation had an adjusted 3-year cumulative incidence of relapse of 20%, 27%, and 22%; 1-year transplant-related mortality (TRM) of 16%, 18%, and 23%; adjusted 3-year leukemia-free survival (LFS) of 54%, 48%, and 47%; and 3-year overall survival (OS) of 63%, 59%, and 54% (all P values >.40). Multivariable analysis confirmed that consolidation was not prognostic for LFS (relative risk, 1.20, 95% confidence interval, .86 to 1.67; P = .28 for no consolidation; RR, 1.18, 95% confidence interval, .79 to 1.76; P = .41 for 1 cycle versus ≥2 cycles = reference). Similarly, consolidation was not associated with OS, relapse, TRM, or graft-versus-host disease. We conclude that consolidation chemotherapy does not appear to provide added benefit in adult ALL patients with available donors who undergo myeloablative alloHCT in CR1.
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El Fakih R, Ahmed S, Alfraih F, Hanbali A. Hematopoietic cell transplantation for acute lymphoblastic leukemia in adult patients. Hematol Oncol Stem Cell Ther 2017. [DOI: 10.1016/j.hemonc.2017.05.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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van der Holt B, Middeldorp S, Meijers JCM, Cornelissen JJ, Bajetta M, Biemond BJ, Lauw MN. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation. Thromb Haemost 2017; 109:633-42. [DOI: 10.1160/th12-11-0845] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Accepted: 01/11/2013] [Indexed: 01/19/2023]
Abstract
SummaryTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle 1 of ALL treatment in adult patients. Secondly, we explored potential etiologic factors for VTE and the clinical impact of VTE on ALL outcome. We retrospectively assessed symptomatic VTE incidence and use of thromboprophylaxis in 240 adults treated for newly diagnosed ALL in the Dutch-Belgian HOVON-37 multicentre study (1999–2005). Potential etiologic factors were explored by analysis of patient and disease characteristics, impact of VTE on ALL outcome by analysis of complete remission and overall survival rates. Symptomatic VTE was observed in 24 of 240 patients (10%). Thromboprophylaxis differed by centre (prophylactic fresh frozen plasma (FFP) supplementation or no thromboprophylaxis) and was applied only during L-asparaginase in cycle 1. VTE incidence was significantly lower with FFP supplementation than without FFP (6% vs. 19%; adjusted odds ratio [OR] 0.28; 95% confidence interval [CI] 0.10–0.73). FFP did not influence antithrombin or fibrinogen plasma levels. Patients with VTE in cycle 1 had a significantly poorer complete remission rate (adjusted OR 0.18; 95% CI 0.07–0.50), particularly patients with cerebral venous thrombosis (adjusted OR 0.17; 95% CI 0.04–0.65). Our study suggests that prophylactic FFP supplementation effectively reduces symptomatic VTE incidence during ALL treatment in adults. This should be confirmed in a randomised controlled trial.
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Haploidentical transplant in patients with myelodysplastic syndrome. Blood Adv 2017; 1:1876-1883. [PMID: 29296834 DOI: 10.1182/bloodadvances.2017007146] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 07/03/2017] [Indexed: 12/28/2022] Open
Abstract
The only curative treatment in patients with intermediate or high-risk myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), which usually results in a long-term, disease-free survival rate of between 30% and 50%, depending on the disease risk and the type of donor. In patients without an HLA-matched sibling donor, a family haploidentical donor is an alternative option. The present study reports the European Group for Blood and Marrow Transplantation activity for haploidentical transplantation in MDS patients. A total of 228 patients transplanted from a mismatched HLA-related donor between 2007 and 2014 were studied. The median age at transplant was 56 years. Eighty-four (37%) patients had MDS transformed into acute myeloid leukemia at the time of transplant. Ex vivo T-cell depletion was used in 34 patients. One hundred ninety-four patients received a T-cell replete transplant and 102 patients received posttransplant cyclophosphamide (PT-CY) as graft-versus-host disease (GVHD) prophylaxis. The cumulative incidences of acute and chronic GVHD in PT-CY vs other patients were 25% vs 37% and 37% vs 24%, respectively. The cumulative incidence of nonrelapse mortality was 55% in patients who did not receive PT-CY (no PT-CY) and 41% in patients who did receive PT-CY. Three-year overall survival was 28% in no PT-CY patients and 38% in PT-CY patients. In multivariable analysis, the main risk factors were the intensity of the conditioning regimen and the use of PT-CY. In conclusion, the outcomes of MDS patients who received an haploidentical transplant are close to the results other transplantations from HLA-mismatched donors with approximately one-third of patients alive and free of disease 3 years after transplant, and the use of PT-CY may improve their outcomes.
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Inbar T, Rowe JM, Horowitz NA. Which patients should I transplant with acute lymphoblastic leukemia? Best Pract Res Clin Haematol 2017; 30:249-260. [DOI: 10.1016/j.beha.2017.07.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 07/05/2017] [Accepted: 07/10/2017] [Indexed: 12/18/2022]
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Parovichnikova EN, Troitskaya VV, Sokolov AN, Bondarenko SN, Gavrilina OA, Baskhaeva GA, Biderman BV, Lukyanova IA, Kuz'mina LA, Klyasova GA, Kravchenko SK, Gribanova EO, Zvonkov EE, Akhmerzaeva ZK, Baranova OY, Kaporskaya TS, Ryltsova TV, Zotina EN, Zinina EE, Samoilova OS, Kaplanov KD, Gavrilova LV, Konstantinova TS, Lapin VA, Pristupa AS, Eluferyeva AS, Obukhova TN, Piskunova IS, Gal'tseva IV, Dvirnyk VN, Rusinov MA, Kulikov SM, Savchenko VG. [Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian prospective multicenter study ALL-2009]. TERAPEVT ARKH 2017; 89:10-17. [PMID: 28766535 DOI: 10.17116/terarkh201789710-17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
AIM To analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells). SUBJECTS AND METHODS The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in 9.4·109/l (0.4-899.0), lactate dehydrogenase in 901 IU (31-13 059), an initial central nervous system lesion in 17 (8.7%), mediastinal injury in 3 (1.5%), and splenomegaly in 111 (57.2%). The results of standard cytogenetic analysis are known in 113 (60.4%) patients. Normal karyotypes were detected in 49 (54.5%) out of the patients; t(4;11) in 9 (5.4%), t(1;19) in 2 (1.2%), and other karyotypic abnormalities in 53 (46.9%). Thirteen (7.8%) patients underwent allogeneic hematopoietic stem cell transplantation in first complete remission (CR); their proportion did not differ in the federal and regional centers. RESULTS The frequency of CR achievement was the same in the federal and regional centers and generally amounted to 87.5%. Early (8.8%) and CR (9.6%) mortality rates remained high despite the low aggressiveness of cytotoxic action, necessitating the improvement of auxiliary treatment. The five-year overall survival (OS) rates vary considerably in the federal and regional centers (72.6 and 43.8%), the relapse-free survival (RFS) (70.2 and 53.4%) and recurrence risk (23.1 and 36.5%) are comparable. This suggests that the non-intensive, but continuous exposure principle built in the ALL-2009 protocol makes it possible to reproduce the envisaged treatment program and to achieve satisfactory results. CONCLUSION The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.
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Affiliation(s)
- E N Parovichnikova
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - V V Troitskaya
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - A N Sokolov
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - S N Bondarenko
- I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
| | - O A Gavrilina
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - G A Baskhaeva
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - B V Biderman
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - I A Lukyanova
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - L A Kuz'mina
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - G A Klyasova
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - S K Kravchenko
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - E O Gribanova
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - E E Zvonkov
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - Z Kh Akhmerzaeva
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - O Yu Baranova
- N.N. Blokhin Russian Cancer Research Center, Moscow, Russia
| | - T S Kaporskaya
- Order of the Badge of Honor Irkutsk Regional Clinical Hospital, Irkutsk, Russia
| | | | - E N Zotina
- Kirov Research Institute of Hematology and Blood Transfusion, Federal Biomedical Agency of Russia, Kirov, Russia
| | - E E Zinina
- Surgut District Clinical Hospital, Surgut, Russia
| | - O S Samoilova
- N.A. Semashko Nizhny Novgorod Regional Clinical Hospital, Nizhny Novgorod, Russia
| | - K D Kaplanov
- Volgograd Regional Clinical Oncology Dispensary One, Volgograd, Russia
| | - L V Gavrilova
- Mordovian Republican Clinical Hospital, Saransk, Russia
| | | | - V A Lapin
- Yaroslavl Regional Clinical Hospital, Yaroslavl, Russia
| | | | - A S Eluferyeva
- V.D. Seredavin Samara Regional Clinical Hospital, Samara, Russia
| | - T N Obukhova
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - I S Piskunova
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - I V Gal'tseva
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - V N Dvirnyk
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - M A Rusinov
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - S M Kulikov
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
| | - V G Savchenko
- National Research Center for Hematology, Ministry of Health of Russia, Moscow, Russia
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Affiliation(s)
- Ibrahim Aldoss
- Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA, USA
| | - Anthony S. Stein
- Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA, USA
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