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Goyal A, O'Leary D, Dabaja B, Weng WK, Zain J, Cutler C, Guitart J, Kim YH, Geskin LJ, Hoppe RT, Wilson LD, Beaven AW, Horwitz S, Allen PB, Barta SK, Bohjanen K, Brammer JE, Carter JB, Comfere N, DeSimone JA, Dusenbery K, Duvic M, Huen A, Jagadeesh D, Kelsey CR, Khodadoust MS, Lechowicz MJ, Mehta-Shah N, Moskowitz AJ, Olsen EA, Poh C, Pro B, Querfeld C, Sauter C, Sokol L, Sokumbi O, Wilcox RA, Zic JA, Gru A, Hamadani M, Foss F. ASTCT and USCLC clinical practice recommendations for allogeneic stem cell transplant in mycosis fungoides and Sézary syndrome. J Am Acad Dermatol 2025:S0190-9622(25)00594-8. [PMID: 40199382 DOI: 10.1016/j.jaad.2025.04.005] [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: 09/19/2024] [Revised: 03/30/2025] [Accepted: 04/02/2025] [Indexed: 04/10/2025]
Abstract
INTRODUCTION Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma. While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease. SS is an aggressive cutaneous T-cell lymphoma associated with high morbidity and mortality secondary to immune compromise and opportunistic infection. Although allogeneic hematopoietic cell transplant (allo-HCT) is currently the only available potentially curative treatment modality for MF/SS and is included in the National Comprehensive Cancer Network and the American Society for Transplantation and Cellular Therapy treatment guidelines, there is no published guidance regarding referral criteria, timing and allo-HCT approach to help guide clinicians caring for these patients. METHODS Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), nontransplant hematology/oncology (n = 8), and radiation oncology (n = 5) from across the United States. Consensus required agreement of ≥75% of participants. RESULTS Sixteen consensus statements were generated on 4 topics: 1) criteria for referral for consideration for allo-HCT, 2) allo-HCT preparative regimens and procedures, 3) disease status at the time of allo-HCT, and 4) multidisciplinary management in the pre- and post-transplant settings. CONCLUSION These clinical practice guidelines provide a framework for decision-making regarding allo-HCT for MF/SS and highlight areas for future prospective investigation.
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Affiliation(s)
- Amrita Goyal
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota.
| | - Daniel O'Leary
- Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota
| | - Bouthaina Dabaja
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wen-Kai Weng
- Blood and Marrow Transplantation, and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Jasmine Zain
- Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California
| | - Corey Cutler
- Division of Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Joan Guitart
- Department of Dermatology, Northwestern Feinberg School of Medicine, Evanston, Illinois
| | - Youn H Kim
- Division of Oncology, Departments of Dermatology and Medicine, Stanford University, Stanford, California
| | - Larisa J Geskin
- Department of Dermatology, Columbia University, New York, New York
| | - Richard T Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, California
| | - Lynn D Wilson
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut
| | - Anne W Beaven
- Division of Hematology, University of North Carolina, Chapel Hill, North Carolina
| | - Steve Horwitz
- Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Pamela B Allen
- Department of Hematology & Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia
| | - Stefan K Barta
- Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kimberly Bohjanen
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota
| | - Jonathan E Brammer
- Division of Hematology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio
| | - Joi B Carter
- Department of Dermatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
| | - Nneka Comfere
- Departments of Dermatology and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota
| | - Jennifer A DeSimone
- Department of Dermatology, University of Virginia Schar Cancer Institute, Fairfax, Virginia
| | - Kathryn Dusenbery
- Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota
| | - Madeleine Duvic
- Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Auris Huen
- Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Deepa Jagadeesh
- Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio
| | - Chris R Kelsey
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
| | - Michael S Khodadoust
- Division of Oncology, Department of Medicine, Stanford University, Stanford, California
| | - Mary Jo Lechowicz
- Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia
| | - Neha Mehta-Shah
- Division of Oncology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Alison J Moskowitz
- Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Elise A Olsen
- Departments of Dermatology and Medicine, Duke University Medical Center, Durham, North Carolina
| | - Christina Poh
- Division of Hematology and Oncology, University of Washington, Seattle, Washington
| | - Barbara Pro
- Department of Hematology and Oncology, New York Presbyterian - Columbia University Irving Medical Center, New York, New York
| | - Christiane Querfeld
- Division of Dermatology, Department of Pathology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Craig Sauter
- Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio
| | - Lubomir Sokol
- Malignant Hematology, Moffitt Cancer Center, Tampa, Florida
| | - Olayemi Sokumbi
- Departments of Dermatology and Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, Florida
| | - Ryan A Wilcox
- Division of Internal Medicine, Hematology/Oncology, University of Michigan, Ann Arbor, Michigan
| | - John A Zic
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Alejandro Gru
- Department of Dermatology, Columbia University, New York, New York
| | - Mehdi Hamadani
- Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Francine Foss
- Department of Hematology/Oncology, Yale University School of Medicine, New Haven, Connecticut
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Purnak S, Hosing C, Dabaja B, Bassett RL, Huen A, Duvic M. On the Way to Curing Advanced-Stage Mycosis Fungoides/Sézary Syndrome. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:827-836. [PMID: 39107202 DOI: 10.1016/j.clml.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/05/2024] [Accepted: 07/11/2024] [Indexed: 08/09/2024]
Abstract
INTRODUCTION/BACKGROUND Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have poor prognosis with median survivals of less than 5 years. Although a variety of treatments are approved for MF/SS patients, durable complete remissions (CR) are rare. PATIENTS AND METHODS Advanced-stage MF or SS patients who achieved CR and maintained in CR or stage IA for more than 10 years were identified by a retrospective search of the principal investigator's database. RESULTS Of 2266 patients diagnosed with MF or SS, 23 patients with advanced-stage MF/SS (6 IIB, 1 IIIB, 5 IVA1, 3 IVA2, 8 IVB) who achieved CR and maintained in CR or stage IA for ≥ 10 years were identified. As final/curative treatment, 11 patients underwent allogeneic stem cell transplantation (SCT). Most patients presented at young age, underwent SCT with reduced intensity conditioning regimen, had matched related donors, and controllable post-transplant graft versus host disease. Eleven patients were treated with TSEB as part of combined modality protocol in 2 patients and debulking therapy before allogeneic SCT in 9 patients. Five stage IIB patients achieved CR with radiotherapy. Four patients with blood involvement were treated with extracorporeal photopheresis (ECP) in combination with long-term antibiotics and immunomodulatory agents. Long-term antibiotics were given to 14 patients. CONCLUSION TSEB followed by allogeneic SCT, radiotherapy, ECP plus long-term antibiotics and immunomodulatory agents were the most common curative/final treatments found in our patients. We are reporting the details of our long-term complete responders' treatment course in the hopes of obtaining more cure responses in the future.
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Affiliation(s)
- Seda Purnak
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX.
| | - Chitra Hosing
- Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bouthaina Dabaja
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Roland L Bassett
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Auris Huen
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Madeleine Duvic
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Goyal A, O'Leary D, Dabaja B, Weng WK, Zain J, Cutler C, Guitart J, Kim YH, Geskin LJ, Hoppe RT, Wilson LD, Beaven AW, Horwitz S, Allen PB, Barta SK, Bohjanen K, Brammer JE, Carter JB, Comfere N, DeSimone JA, Dusenbery K, Duvic M, Huen A, Jagadeesh D, Kelsey CR, Khodadoust MS, Lechowicz MJ, Mehta-Shah N, Moskowitz AJ, Olsen EA, Poh C, Pro B, Querfeld C, Sauter C, Sokol L, Sokumbi O, Wilcox RA, Zic JA, Hamadani M, Foss F. ASTCT and USCLC Clinical Practice Recommendations for Allogeneic Stem Cell Transplant in Mycosis Fungoides and Sézary Syndrome. Transplant Cell Ther 2024; 30:1047-1060. [PMID: 39222792 DOI: 10.1016/j.jtct.2024.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant hematology/oncology (n = 8), and radiation oncology (n = 5) from across the United States. Consensus required agreement of ≥75% of participants. Sixteen consensus statements were generated on four topics: (1) criteria for referral for consideration for allo-HCT, (2) allo-HCT preparative regimens and procedures (3) disease status at the time of allo-HCT, and (4) multidisciplinary management in the pre- and post-transplant settings. These clinical practice guidelines provide a framework for decision-making regarding allo-HCT for MF/SS and highlight areas for future prospective investigation.
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Affiliation(s)
- Amrita Goyal
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota.
| | - Daniel O'Leary
- Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota
| | - Bouthaina Dabaja
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wen-Kai Weng
- Blood and Marrow Transplantation, and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Jasmine Zain
- Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California
| | - Corey Cutler
- Division of Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Joan Guitart
- Department of Dermatology, Northwestern Feinberg School of Medicine, Evanston, Illinois
| | - Youn H Kim
- Departments of Dermatology and Medicine/Division of Oncology, Stanford University, Stanford, California
| | - Larisa J Geskin
- Department of Dermatology, Columbia University, New York, New York
| | - Richard T Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, California
| | - Lynn D Wilson
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut
| | - Anne W Beaven
- Division of Hematology, University of North Carolina, Chapel Hill, North Carolina
| | - Steve Horwitz
- Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Pamela B Allen
- Department of Hematology & Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia
| | - Stefan K Barta
- Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kimberly Bohjanen
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota
| | - Jonathan E Brammer
- Division of Hematology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio
| | - Joi B Carter
- Department of Dermatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
| | - Nneka Comfere
- Departments of Dermatology and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota
| | - Jennifer A DeSimone
- Department of Dermatology, University of Virginia Schar Cancer Institute, Fairfax, Virginia
| | - Kathryn Dusenbery
- Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota
| | - Madeleine Duvic
- Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Auris Huen
- Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Deepa Jagadeesh
- Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio
| | - Chris R Kelsey
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
| | - Michael S Khodadoust
- Division of Oncology, Department of Medicine, Stanford University, Stanford, California
| | - Mary Jo Lechowicz
- Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia
| | - Neha Mehta-Shah
- Department of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Alison J Moskowitz
- Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Elise A Olsen
- Departments of Dermatology and Medicine, Duke University Medical Center, Durham, North Carolina
| | - Christina Poh
- Division of Hematology and Oncology, University of Washington, Seattle, Washington
| | - Barbara Pro
- Department of Hematology and Oncology, New York Presbyterian - Columbia University Irving Medical Center, New York, New York
| | - Christiane Querfeld
- Department of Pathology, Division of Dermatology & Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Craig Sauter
- Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio
| | - Lubomir Sokol
- Malignant Hematology, Moffitt Cancer Center, Tampa, Florida
| | - Olayemi Sokumbi
- Departments of Dermatology and Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, Florida
| | - Ryan A Wilcox
- Division of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan
| | - John A Zic
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Mehdi Hamadani
- Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Francine Foss
- Department of Hematology/Oncology, Yale University School of Medicine, New Haven, Connecticut
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Violetti SA, Ardigò M, Fava P, Gritti G, Morsia E, Onida F, Paulli M, Pileri A, Quaglino P, Rupoli S, Teoli M, Vezzoli P. Multidisciplinary and personalized approach to the management of mycosis fungoides with chlormethine gel: a collection of clinical experiences. Drugs Context 2024; 13:2024-6-1. [PMID: 39416772 PMCID: PMC11482090 DOI: 10.7573/dic.2024-6-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 07/25/2024] [Indexed: 10/19/2024] Open
Abstract
Topical chlormethine (CL) gel formulation was approved by the EMA in 2017 for the treatment of adult patients with mycosis fungoides (MF). To expand the knowledge on the management of MF, this paper provides an overview of clinical practice evidence about the MF diagnostic phase and a collection of clinical experiences to better characterize the use of CL gel in daily practice. Collected cases underline the importance of the concomitant biopsy and clinical evaluation in the diagnostic phase, with the contribution of a multidisciplinary team, and support the use of CL gel as a first-line or adjuvant treatment in selected patients.
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Affiliation(s)
- Silvia Alberti Violetti
- Dermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Marco Ardigò
- Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Paolo Fava
- Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy
| | - Giuseppe Gritti
- Hematology and BMT Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Erika Morsia
- Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy
| | - Francesco Onida
- Hematology and BMT Unit, ASST Fatebenefratelli-Sacco – University of Milan, Italy
| | - Marco Paulli
- Unità di Anatomia Patologica, Dipartimento di Medicina Molecolare, Università degli Studi di Pavia, Pavia, Italy
| | - Alessandro Pileri
- Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Pietro Quaglino
- Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy
| | - Serena Rupoli
- Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy
| | - Miriam Teoli
- Porphyria and Rare Diseases Unit, San Gallicano Dermatological Institute – IRCCS, via Chianesi 53, 00144 Rome, Italy
| | - Pamela Vezzoli
- Dermatology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
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Lechowicz MJ, Smith C, Ristuccia R, Dwyer K. Allogeneic hematopoietic stem cell transplantation after mogamulizumab in T-cell lymphoma patients: a retrospective analysis. Int J Hematol 2024; 119:736-744. [PMID: 38532079 PMCID: PMC11136860 DOI: 10.1007/s12185-024-03753-9] [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: 08/08/2023] [Revised: 02/22/2024] [Accepted: 03/06/2024] [Indexed: 03/28/2024]
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapy for patients with T-cell lymphomas, including cutaneous T-cell lymphoma (CTCL), adult T-cell lymphoma (ATL), and peripheral T-cell lymphoma (PTCL). Mogamulizumab is an anti-CCR4 antibody that has been associated with an increased risk of transplant-related complications in retrospective analyses of ATL, particularly when administered within 50 days before transplantation. This post hoc analysis of 3 clinical trials examined safety and outcome data for 32 patients with CTCL (n = 23), ATL (n = 7), or PTCL (n = 2) who underwent allo-HSCT after mogamulizumab treatment. Overall, 22 patients (69%) were known to have graft-versus-host disease (GVHD), 8 patients (25%) did not report GVHD, and 2 patients (6%) had unknown GVHD status. Fourteen patients with known GVHD underwent transplantation between 50 and 365 days after their last dose of mogamulizumab, while 2 underwent transplantation within 50 days after treatment. Based on this limited evidence, GVHD was not associated with the time interval from last mogamulizumab dose to transplantation.
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Affiliation(s)
| | - Christy Smith
- Medical Affairs Oncology, Kyowa Kirin, Inc, Princeton, NJ, USA
| | | | - Karen Dwyer
- Medical Sciences, Kyowa Kirin, Inc, Princeton, NJ, USA
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Morris SL, Thomas BR, Palanicawandar R, Whittaker S, Child F, Wain M, Sim V, Szydlo R, Mangar S, Olavarria E, Lozano Cerrada S, Muzamil A, Kanfer E. Long term outcomes of nonmyeloablative allogeneic stem cell transplantation with TSEB TLI and ATG for Mycosis Fungoides and Sezary Syndrome. Bone Marrow Transplant 2024; 59:874-879. [PMID: 38472408 PMCID: PMC11161400 DOI: 10.1038/s41409-024-02236-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/22/2024] [Accepted: 01/30/2024] [Indexed: 03/14/2024]
Abstract
Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a non-myeloablative allogeneic stem cell transplantation regimen consisting of total skin electron beam therapy, total lymphoid irradiation and antithymocyte globulin. Our prospective cohort consisted of 41 patients with a higher proportion of MF (34MF, 7SS). Acute GVHD Grade 2 to 4 was seen in 31.7% and chronic GVHD Grade 2 to 4 in 24%. The cumulative incidence of non-relapse mortality was 9.8% at 1 year and 12.6% at 2 years. At Day +90 post-transplant 66% of patients had a complete response (CR). With a median post-transplant follow up of 5.27 years, the 5-year overall survival rate was 37.7% (MF 36.7%, SS 57.1%). The 5-year cumulative incidence of progressive disease or relapse was 52.7% in all patients but only 20.8% in those with CR at transplant compared to 70.6% in those not in CR at transplant (p = 0.006). Long term survival is possible in advanced MF and SS with non-myeloablative transplantation and outcomes are improved in patients with CR at transplant.
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Affiliation(s)
| | | | | | | | | | - M Wain
- Guys Hospital, London, UK
| | - V Sim
- Guys Hospital, London, UK
| | - R Szydlo
- Hammersmith Hospital, London, UK
| | - S Mangar
- Hammersmith Hospital, London, UK
| | | | | | | | - E Kanfer
- Hammersmith Hospital, London, UK
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7
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Goyal A, O'Leary D, Foss F. Allogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis. Bone Marrow Transplant 2024; 59:41-51. [PMID: 37853164 DOI: 10.1038/s41409-023-02122-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 09/08/2023] [Accepted: 10/04/2023] [Indexed: 10/20/2023]
Abstract
Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS.
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Affiliation(s)
- Amrita Goyal
- Department of Dermatology, University of Minnesota, Minneapolis, MN, USA.
| | - Daniel O'Leary
- Division of Hematology, Oncology, and Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA
| | - Francine Foss
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
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Goyal A, Foss F. Allogeneic transplantation and cellular therapies in cutaneous T-cell lymphoma. Expert Rev Anticancer Ther 2024; 24:41-58. [PMID: 38224371 DOI: 10.1080/14737140.2024.2305356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 01/10/2024] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease control, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option for advanced stage MF and SS. CAR T-cell therapy is a promising new avenue for treatment. AREAS COVERED In this review, we discuss the evidence supporting the use of allo-HSCT for the treatment of MF/SS, including disease status at the time of transplant, conditioning regimen, total body irradiation (TBI), and donor lymphocyte infusion (DLI). We also address the potential role for CAR T-cell therapy in CTCL. EXPERT OPINION Allo-HSCT is an effective treatment for patients with advanced MF and SS. However, significant research is required to determine optimal treatment protocols. Data support the use of reduced-intensity conditioning regimens and suggests that the use of TBI for debulking of skin disease may result in more durable remissions. Donor lymphocyte infusions (DLI) appear to be particularly effective in inducing complete remission in MF/SS patients with relapsed or residual disease. Challenges with CAR-T therapies in T-cell lymphoma include T-cell fratricide due to shared antigens on malignant and nonmalignant T-cells, penetrance into the skin compartment, and CAR-T cell persistence.
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Affiliation(s)
- Amrita Goyal
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Francine Foss
- Department of Hematology/Oncology, Yale School of Medicine, New Haven, Connecticut, USA
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Lachance M, Thibeault MM. Clinical characteristics, initial treatment, and prognosis of mycosis fungoides and Sézary syndrome: A retrospective, single-center study at the Centre Hospitalier Universitaire of Quebec. Ann Dermatol Venereol 2023; 150:276-280. [PMID: 37777355 DOI: 10.1016/j.annder.2023.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 05/03/2023] [Accepted: 06/26/2023] [Indexed: 10/02/2023]
Affiliation(s)
- M Lachance
- Department of Dermatology, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada.
| | - M-M Thibeault
- Department of Dermatology, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada
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10
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Latzka J, Assaf C, Bagot M, Cozzio A, Dummer R, Guenova E, Gniadecki R, Hodak E, Jonak C, Klemke CD, Knobler R, Morrris S, Nicolay JP, Ortiz-Romero PL, Papadavid E, Pimpinelli N, Quaglino P, Ranki A, Scarisbrick J, Stadler R, Väkevä L, Vermeer MH, Wehkamp U, Whittaker S, Willemze R, Trautinger F. EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023. Eur J Cancer 2023; 195:113343. [PMID: 37890355 DOI: 10.1016/j.ejca.2023.113343] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/28/2023] [Accepted: 08/23/2023] [Indexed: 10/29/2023]
Abstract
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
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Affiliation(s)
- Johanna Latzka
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria; Karl Landsteiner Institute of Dermatological Research, Department of Dermatology and Venereology, University Hospital of St. Pölten, St. Pölten, Austria.
| | - Chalid Assaf
- Department of Dermatology, HELIOS Klinikum Krefeld, Krefeld, Germany; Institute for Molecular Medicine, Medical School Hamburg, University of Applied Sciences and Medical University, Hamburg, Germany; Department of Dermatology, HELIOS Klinikum Schwerin, University Campus of The Medical School Hamburg, Schwerin, Germany
| | - Martine Bagot
- Department of Dermatology, Hopital Saint Louis, Université Paris Cité, INSERM U976, Paris, France
| | - Antonio Cozzio
- Department of Dermatology and Allergology, Kantonspital St. Gallen, St. Gallen, Switzerland
| | - Reinhard Dummer
- Department of Dermatology, University of Zurich, Zurich, Switzerland
| | - Emmanuella Guenova
- Department of Dermatology, University Hospital of Lausanne and Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Robert Gniadecki
- Department of Dermatology, University of Copenhagen, Copenhagen, Denmark; Division of Dermatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Emmilia Hodak
- Cutaneous Lymphoma Unit, Davidoff Cancer Center, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Constanze Jonak
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | | | - Robert Knobler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Stephen Morrris
- Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, London, UK
| | - Jan P Nicolay
- Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany
| | - Pablo L Ortiz-Romero
- Department of Dermatology, Hospital Universitario 12 de Octubre, Institute i+12, CIBERONC, Medical School, University Complutense, Madrid, Spain
| | - Evangelia Papadavid
- National and Kapodistrian University of Athens, 2nd Department of Dermatology and Venereology, Attikon General Hospital, University of Athens, Chaidari, Greece
| | - Nicola Pimpinelli
- Department of Health Sciences, Division of Dermatology, University of Florence, Florence, Italy
| | - Pietro Quaglino
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - Annamari Ranki
- Department of Dermatology and Allergology, Inflammation Center, Helsinki University Central Hospital, Helsinki, Finland
| | - Julia Scarisbrick
- Department of Dermatology, University Hospital Birmingham, Birmingham, UK
| | - Rudolf Stadler
- University Department of Dermatology, Venereology, Allergology and Phlebology, Skin Cancer Center, Johannes Wesling Medical Centre Minden, Ruhr University Bochum, Bochum, Germany
| | - Liisa Väkevä
- Department of Dermatology and Allergology, Inflammation Center, Helsinki University Central Hospital, Helsinki, Finland
| | - Maarten H Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ulrike Wehkamp
- Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Medical Department, Medical School of Hamburg, Hamburg, Germany
| | - Sean Whittaker
- St. John's Institute of Dermatology, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Franz Trautinger
- Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria; Karl Landsteiner Institute of Dermatological Research, Department of Dermatology and Venereology, University Hospital of St. Pölten, St. Pölten, Austria
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Iqbal M, Kharfan-Dabaja MA. Cogent data on allogeneic haematopoietic stem-cell transplantation efficacy in advanced cutaneous T-cell lymphoma. Lancet 2023; 401:1906-1907. [PMID: 37105211 DOI: 10.1016/s0140-6736(23)00631-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/23/2023] [Indexed: 04/29/2023]
Affiliation(s)
- Madiha Iqbal
- Department of Hematology and Oncology, Mayo Clinic Cancer Center, NCI Designated Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
| | - Mohamed A Kharfan-Dabaja
- Department of Hematology and Oncology, Mayo Clinic Cancer Center, NCI Designated Comprehensive Cancer Center, Jacksonville, FL 32224, USA
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12
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de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet 2023; 401:1941-1950. [PMID: 37105210 DOI: 10.1016/s0140-6736(23)00329-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 01/26/2023] [Accepted: 02/10/2023] [Indexed: 04/29/2023]
Abstract
BACKGROUND Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.
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Affiliation(s)
- Adèle de Masson
- Department of Dermatology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France.
| | - Marie Beylot-Barry
- Department of Dermatology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Institut National de la Santé et de la Recherche Médicale U1312, Bordeaux Institute of Oncology, Team 5, University of Bordeaux, Bordeaux, France
| | - Caroline Ram-Wolff
- Department of Dermatology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Jean-Baptiste Mear
- Department of Hematology, L'Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France
| | - Stéphane Dalle
- Department of Dermatology, Hôpital Lyon-Sud, Lyon, France
| | - Michel d'Incan
- Department of Dermatology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
| | - Saskia Ingen-Housz-Oro
- Department of Dermatology, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, University Paris-Est Créteil, Créteil, France
| | - Corentin Orvain
- Department of Hematology, Centre Hospitalier Universitaire d'Angers, Angers, France; Fédération Hospitalo-Universitaire Grand-Ouest Acute Leukemia, Angers, France; Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1307, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6075, Nantes Université, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, Université d'Angers, Angers, France
| | - Julie Abraham
- Department of Hematology, Centre Hospitalier Universitaire de Limoges, Limoges, France
| | - Olivier Dereure
- Department of Dermatology and Institut National de la Santé et de la Recherche Médicale U1058 Pathogenesis and Control of Chronic and Emergent Infections, University of Montpellier, Montpellier, France
| | - Amandine Charbonnier
- Department of Hematology, Centre Hospitalier Universitaire d'Amiens, Amiens, France
| | - Jérôme Cornillon
- Department of Clinical Hematology and Cellular Therapy, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France
| | - Christine Longvert
- Department of Dermatology, Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France
| | - Stéphane Barete
- Department of Dermatology, Centre Hospitalier Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Serge Boulinguez
- Department of Dermatology, Centre Hospitalier Universitaire Toulouse, Toulouse, France
| | - Ewa Wierzbicka-Hainaut
- Department of Dermatology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
| | - François Aubin
- Department of Dermatology, Centre Hospitalier Universitaire de Besançon, Besançon, France
| | - Marie-Thérèse Rubio
- Department of Hematology, Hôpital Brabois, Centre Hospitalier Régional Universitaire Nancy, Nancy, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 7365, Ingéniérie Moléculaire et Physiopathologie Articulaire, Biopole, University of Lorraine, Nancy, France
| | - Marc Bernard
- Department of Hematology, L'Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France
| | - Aline Schmidt-Tanguy
- Department of Hematology, Centre Hospitalier Universitaire d'Angers, Angers, France
| | - Roch Houot
- Department of Hematology, L'Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France; Institut National de la Santé et de la Recherche Médicale U1236, Rennes, France
| | - Anne Pham-Ledard
- Department of Dermatology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Institut National de la Santé et de la Recherche Médicale U1312, Bordeaux Institute of Oncology, Team 5, University of Bordeaux, Bordeaux, France
| | - David Michonneau
- Department of Hematology and Bone Marrow Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Pauline Brice
- Department of Hemato-Oncology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | | | - Jean-David Bouaziz
- Department of Dermatology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Florent Grange
- Department of Dermatology, Centre Hospitalier de Valence, Valence, France
| | - Hélène Moins-Teisserenc
- Hematology Laboratory, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris Cité, Paris, France
| | - Katayoun Jondeau
- Department of Hematology, Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France
| | - Laurence Michel
- Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Samia Mourah
- Department of Tumor Genomics and Pharmacology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Maxime Battistella
- Pathology Laboratory, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Etienne Daguindau
- Department of Hematology, Centre Hospitalier Universitaire de Besançon, Besançon, France
| | - Michael Loschi
- Department of Hematology, Hôpital L'Archet, Centre Hospitalier Universitaire de Nice, Nice, France
| | - Alexandra Picard
- Department of Dermatology, Centre Hospitalier Universitaire de Nice, Nice, France
| | - Nathalie Franck
- Department of Dermatology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Natacha Maillard
- Department of Hematology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
| | - Anne Huynh
- Department of Hematology, Centre Hospitalier Universitaire, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
| | - Stéphanie Nguyen
- Department of Hematology, Centre Hospitalier Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Ambroise Marçais
- Department of Hematology, Centre Hospitalier Universitaire Necker, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Guillaume Chaby
- Department of Dermatology, Centre Hospitalier Universitaire d'Amiens, Amiens, France
| | - Patrice Ceballos
- Department of Hematology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| | - Yannick Le Corre
- Department of Dermatology, Centre Hospitalier Universitaire d'Angers, Angers, France
| | - Sébastien Maury
- Department of Hematology, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Jacques-Olivier Bay
- Department of Hematology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
| | - Henri Adamski
- Department of Dermatology, L'Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France
| | - Emmanuel Bachy
- Department of Hematology, Centre Hospitalier Universitaire de Lyon, Lyon, France
| | - Edouard Forcade
- Department of Clinical Hematology and Cellular Therapy, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France
| | - Gérard Socié
- Department of Hematology and Bone Marrow Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Martine Bagot
- Department of Dermatology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut National de la Santé et de la Recherche Médicale U976 Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France; Université Paris Cité, Paris, France
| | - Sylvie Chevret
- Department of Biostatistics, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris Cité, Paris, France; Institut National de la Santé et de la Recherche Médicale U1153, Paris, France
| | - Régis Peffault de Latour
- Department of Hematology and Bone Marrow Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris Cité, Paris, France.
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Lee H. Mycosis fungoides and Sézary syndrome. Blood Res 2023; 58:66-82. [PMID: 37105561 PMCID: PMC10133849 DOI: 10.5045/br.2023.2023023] [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: 01/26/2023] [Revised: 04/16/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are a distinct disease entity of cutaneous T-cell lymphoma with heterogenous clinical features and prognosis. MF mainly involves skin and usually shows an indolent and favorable clinical course. In patients with advanced-stage disease, extracutaneous involvement including lymph nodes, viscera, and blood, or large cell transformation may be observed. SS is a leukemic form of advanced-stage MF, characterized by generalized erythroderma. Early-stage MF can be treated with skin-directed therapy. However, patients with refractory or advanced-stage disease are associated with severe symptoms or poor prognosis, requiring systemic therapy. Recent progress in understanding the pathogenesis of MF/SS has contributed to advances in the management of these rare diseases. This review aims to describe the clinical manifestations, diagnosis, risk stratification, and treatment strategy of MF/SS, focusing on the recent updates in the management of these diseases.
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Affiliation(s)
- Hyewon Lee
- Division of Hemato-Oncology, Department of Internal Medicine, and Center for Hematologic Malignancy, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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14
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Atilla PA, Atilla E. Are we there yet? cellular therapies for cutaneous T cell lymphoma. Curr Res Transl Med 2023; 71:103390. [PMID: 37062252 DOI: 10.1016/j.retram.2023.103390] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 03/08/2023] [Accepted: 04/04/2023] [Indexed: 04/18/2023]
Abstract
Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of skin-involved T-cell non-Hodgkin lymphoma which Mycosis Fungoides and Sezary Syndrome are the most common variants. Despite considerable progress in distinguishing the pathophysiology, the treatment options are still limited for advanced-stage disease. Recent approval of novel agents such as vorinostat, brentuximab vedotin and mogamulizumab paved a way. Allogeneic hematopoietic stem cell transplantation has been shown to be a feasible option in selected advanced-stage CTCL patients. Chimeric antigen receptor (CAR) T cells have been promising for the treatment of B-cell tumors and have been approved for second-line treatment in non-Hodgkin's lymphoma. Although several obstacles still need to be addressed, CAR T cell treatment for CTCLs seems not far off. This review discusses new discoveries in pathophysiology, the state of cellular therapies in current practice, challenges for cellular treatment in advanced CTCL, and how to overcome these challenges.
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Affiliation(s)
- Pinar Ataca Atilla
- Ankara University Stem Cell Institute, Ankara, Turkey; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA
| | - Erden Atilla
- Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA; Genyo Centre for Genomics and Oncological Research, Genomic Medicine Department, Pfizer/University of Gradana/Andalusian Regional Government, Health Sciences Technnology Park, Granada, Spain.
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15
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Khodadoust MS, Mou E, Kim YH. Integrating novel agents into the treatment of advanced mycosis fungoides and Sézary syndrome. Blood 2023; 141:695-703. [PMID: 36379025 DOI: 10.1182/blood.2020008241] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/04/2022] [Accepted: 10/31/2022] [Indexed: 11/16/2022] Open
Abstract
Agents targeting the unique biology of mycosis fungoides and Sézary syndrome are quickly being incorporated into clinical management. With these new therapies, we are now capable of inducing more durable responses and even complete remissions in advanced disease, outcomes which were exceedingly rare with prior therapies. Yet, even this new generation of therapies typically produce objective responses in only a minority of patients. As our therapeutic options increase, we are now challenged with selecting treatments from a growing list of options. To gain the full benefit of these novel agents, we must develop strategies to match treatments for the patients most likely to benefit from them. Here, we consider both the current approaches to treatment selection based on clinical features and the future of molecular biomarker-guided therapy for patients with this heterogeneous disease.
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Affiliation(s)
- Michael S Khodadoust
- Division of Oncology, Stanford University, Stanford, CA
- Department of Dermatology, Stanford University, Stanford, CA
| | - Eric Mou
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
| | - Youn H Kim
- Division of Oncology, Stanford University, Stanford, CA
- Department of Dermatology, Stanford University, Stanford, CA
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16
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Hristov AC, Tejasvi T, Wilcox RA. Cutaneous T-cell lymphomas: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol 2023; 98:193-209. [PMID: 36226409 PMCID: PMC9772153 DOI: 10.1002/ajh.26760] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 10/05/2022] [Indexed: 02/04/2023]
Abstract
DISEASE OVERVIEW Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). DIAGNOSIS The diagnosis of MF or SS requires the integration of clinical and histopathologic data. RISK-ADAPTED THERAPY TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or the blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.
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Affiliation(s)
- Alexandra C. Hristov
- Departments of Pathology and Dermatology, 2800 Plymouth Road, Building 35, Ann Arbor, MI 48109-2800
| | - Trilokraj Tejasvi
- Department of Dermatology, 1910 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109
| | - Ryan A. Wilcox
- Correspondence to: Ryan Wilcox, MD, PhD, Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Rogel Cancer Center, 1500 E. Medical Center Drive, Room 4310 CC, Ann Arbor, MI 48109-5948, Phone: (734) 615-9799, Fax: (734) 936-7376,
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17
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Hughes MS, Sterling CH, Varadhan R, Ambinder RF, Jones RJ, Sweren RJ, Rozati S, Bolaños-Meade J, Luznik L, Imus PH, Ali SA, Borrello IM, Huff CA, Jain T, Ambinder A, DeZern AE, Gocke CB, Gladstone DE, Swinnen LJ, Wagner-Johnston ND, Fuchs EJ. Mismatched donor transplantation with post-transplantation cyclophosphamide for advanced cutaneous T-cell lymphoma: a single-center retrospective study. Leuk Lymphoma 2022; 63:2987-2991. [PMID: 35915978 DOI: 10.1080/10428194.2022.2105330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Michael S Hughes
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cole H Sterling
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ravi Varadhan
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Richard F Ambinder
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Richard J Jones
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ronald J Sweren
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sima Rozati
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Javier Bolaños-Meade
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Leo Luznik
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Philip H Imus
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Syed Abbas Ali
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ivan M Borrello
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Carol Ann Huff
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Tania Jain
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alexander Ambinder
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amy E DeZern
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christian B Gocke
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Douglas E Gladstone
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lode J Swinnen
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nina D Wagner-Johnston
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ephraim J Fuchs
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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18
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Weiner DM, Lewis DJ, Spaccarelli NG, Clark RA, Nasta SD, Loren AW, Rook AH, Kim EJ. Management of relapsed cutaneous T-Cell lymphoma following allogeneic hematopoietic stem cell transplantation: Review with representative patient case. Dermatol Ther 2022; 35:e15538. [PMID: 35477952 DOI: 10.1111/dth.15538] [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: 02/14/2022] [Revised: 03/21/2022] [Accepted: 04/26/2022] [Indexed: 11/29/2022]
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with refractory cutaneous T-cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft-versus-lymphoma effect. However, allo-HSCT is not always curative; relapse of CTCL occurs in about half of patients post-transplant. Treatment of relapsed CTCL after allo-HSCT is challenging because post-transplant patients are at high risk of graft-versus-host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies. The benefit of each potential therapy must therefore be weighed against its risk of graft versus host disease (GVHD). In this article, we review the management of relapsed CTCL after allo-HSCT. We begin with an exemplative patient whose relapsed Sezary syndrome was successfully treated without development of GVHD. We also report high-throughput T-cell receptor sequencing data obtained during the patient's disease relapse and remission. We then review general guidelines for management of relapsed CTCL and summarize all reported cases and outcomes of relapsed CTCL after transplant. We conclude by reviewing the current CTCL therapies and their risk of GVHD.
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Affiliation(s)
- David M Weiner
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Daniel J Lewis
- Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Rachael A Clark
- Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA
| | - Sunita D Nasta
- Department of Hematology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alison W Loren
- Department of Hematology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alain H Rook
- Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ellen J Kim
- Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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19
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Angelov D, Dillon J, Mellerick L, Pender E, Bacon L, Lee G, Higgins L, McCarty H, Gillham C, Quinn J, O'Gorman S, Leonard N, McMenamin M, Vandenberghe E. Allogeneic transplantation in Cutaneous T-cell Lymphoma: improved outcomes associated with early transplantation and acute graft versus host disease. Bone Marrow Transplant 2022; 57:1332-1334. [PMID: 35596064 DOI: 10.1038/s41409-022-01713-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 05/10/2022] [Accepted: 05/12/2022] [Indexed: 11/09/2022]
Affiliation(s)
- Daniel Angelov
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland.
| | - James Dillon
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Lisa Mellerick
- Department of Histopathology, St. James's Hospital, Dublin 8, Ireland
| | - Emily Pender
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Larry Bacon
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Greg Lee
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | - Liz Higgins
- Department of Haematology, St. James's Hospital, Dublin 8, Ireland
| | | | - Charles Gillham
- Department of Radiation Oncology, St James's Hospital, Dublin 8, Ireland
| | - John Quinn
- Department of Haematology, Beaumont Hospital, Dublin 9, Ireland
| | - Susan O'Gorman
- Department of Dermatology, St. James's Hospital, Dublin 8, Ireland
| | - Niamh Leonard
- Department of Histopathology, St. James's Hospital, Dublin 8, Ireland
| | - Máirín McMenamin
- Department of Histopathology, St. James's Hospital, Dublin 8, Ireland
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20
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Scarisbrick JJ. The PROCLIPI international registry, an important tool to evaluate the prognosis of cutaneous T cell lymphomas. Presse Med 2022; 51:104123. [PMID: 35490911 DOI: 10.1016/j.lpm.2022.104123] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 04/11/2022] [Indexed: 11/19/2022] Open
Abstract
PROCLIPI is the PROgnostic Cutaneous Lymphoma International Prognostic Index Study with the main aim to produce a prognostic index in mycosis fungoides (MF) and Sezary syndrome (SS). The study prospectively collects clinical, haematological, pathological, imaging, treatment with responses, quality of life and survival data using careful predefined datasets. Patients are subject to a central review to confirm diagnosis. PROCLIPI opened in 2015 and recruitment has been strong with to date 1916 patients recruited from 52 Centres from 19 countries across 6 continents.
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Affiliation(s)
- J J Scarisbrick
- Department of Dermatology, University Hospital Birmingham, Birmingham, B15 2TH, UK.
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21
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Dippel E, Assaf C, Becker JC, von Bergwelt-Baildon M, Bernreiter S, Cozzio A, Eich HT, Elsayad K, Follmann M, Grabbe S, Hillen U, Klapper W, Klemke CD, Loquai C, Meiss F, Mitteldorf C, Wehkamp U, Nashan D, Nicolay JP, Oschlies I, Schlaak M, Stranzenbach R, Moritz R, Stoll C, Vag T, Weichenthal M, Wobser M, Stadler R. S2k-Leitlinie - Kutane Lymphome (ICD10 C82-C86): Update 2021. J Dtsch Dermatol Ges 2022; 20:537-555. [PMID: 35446484 DOI: 10.1111/ddg.14706_g] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
| | - Chalid Assaf
- Klinik für Dermatologie und Venerologie, Helios Klinikum Krefeld
| | | | | | | | - Antonio Cozzio
- Klinik für Dermatologie, Venerologie und Allergologie, Kantonsspital St. Gallen
| | - Hans T Eich
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Münster
| | - Khaled Elsayad
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Münster
| | | | | | - Uwe Hillen
- Klinik für Dermatologie, Universitätsklinikum Essen
| | - Wolfram Klapper
- Institut für Pathologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Claus-Detlev Klemke
- Hautklinik, Städtisches Klinikum Karlsruhe, Akademisches Lehrkrankenhaus der Universität Freiburg, Karlsruhe
| | | | - Frank Meiss
- Klinik für Dermatologie und Venerologie, Universitätsklinik Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Christina Mitteldorf
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen
| | - Ulrike Wehkamp
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | | | - Jan P Nicolay
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinik Mannheim
| | - Ilske Oschlies
- Institut für Pathologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Max Schlaak
- Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin
| | - René Stranzenbach
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum der Ruhr-Universität Bochum
| | - Rose Moritz
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Halle
| | | | - Tibor Vag
- Nuklearmedizinische Klinik, Klinikum Rechts der Isar, Technische Universität München
| | - Michael Weichenthal
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
| | - Marion Wobser
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg
| | - Rudolf Stadler
- Klinik für Dermatologie, Venerologie, Allergologie und Phlebologie, Johannes Wesling Universitätsklinikum Minden, Universitätsklinikum der Ruhr-Universität Bochum
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22
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Dippel E, Assaf C, Becker JC, von Bergwelt‐Baildon M, Bernreiter S, Cozzio A, Eich H
T, Elsayad K, Follmann M, Grabbe S, Hillen U, Klapper W, Klemke C, Loquai C, Meiss F, Mitteldorf C, Wehkamp U, Nashan D, Nicolay JP, Oschlies I, Schlaak M, Stranzenbach R, Moritz R, Stoll C, Vag T, Weichenthal M, Wobser M, Stadler R. S2k-Guidelines - Cutaneous lymphomas (ICD10 C82 - C86): Update 2021. J Dtsch Dermatol Ges 2022; 20:537-554. [PMID: 35446497 PMCID: PMC9325452 DOI: 10.1111/ddg.14706] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Edgar Dippel
- Department of DermatologyHospital LudwigshafenGermany
| | - Chalid Assaf
- Department of Dermatology and VenereologyHelios Hospital KrefeldGermany
| | | | | | | | - Antonio Cozzio
- Department of DermatologyVenereology and AllergologyCanton Hospital St. GallenSwitzerland
| | - Hans
T. Eich
- Department of Radiation Therapy and Radio‐OncologyUniversity Hospital MünsterGermany
| | - Khaled Elsayad
- Department of Radiation Therapy and Radio‐OncologyUniversity Hospital MünsterGermany
| | | | - Stephan Grabbe
- Department of DermatologyUniversity Hospital MainzGermany
| | - Uwe Hillen
- Department of DermatologyUniversity Hospital EssenGermany
| | - Wolfram Klapper
- Institute of PathologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Claus‐Detlev Klemke
- Department of DermatologyMunicipal Hospital of KarlsruheAcademic Teaching Hospital for the University of FreiburgKarlsruheGermany
| | - Carmen Loquai
- Department of DermatologyUniversity Hospital MainzGermany
| | - Frank Meiss
- Department of Dermatology and VenereologyUniversity Hospital Freiburgmedical FacultyAlbert‐Ludwigs University FreiburgGermany
| | - Christina Mitteldorf
- Department of DermatologyVenereology and AllergologyUniversity Hospital GöttingenGermany
| | - Ulrike Wehkamp
- Department of DermatologyVenereology and AllergologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Dorothee Nashan
- Department of DermatologyDortmund Hospital GmbHDortmundGermany
| | - Jan P. Nicolay
- Department of DermatologyVenereology and AllergologyUniversity Hospital MannheimGermany
| | - Ilske Oschlies
- Institute of PathologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Max Schlaak
- Charité
– Universitätsmedizin BerlinDepartment of DermatologyVenereology and AllergologyBerlinGermany
| | - René Stranzenbach
- Department of DermatologyVenereology and AllergologyUniversity Hospital at Ruhr University BochumGermany
| | - Rose Moritz
- Department for DermatologyUniversity Hospital HalleGermany
| | | | - Tibor Vag
- Department of Nuclear MedicineTechnical University of MunichGermany
| | - Michael Weichenthal
- Department of DermatologyVenereology and AllergologyUniversity Hospital Schleswig‐HolsteinCampus KielGermany
| | - Marion Wobser
- Department of DermatologyVenereology and AllergologyUniversity Hospital WürzburgGermany
| | - Rudolf Stadler
- Department of DermatologyVenereologyAllergologyand PhlebologyJohannes Wesling University Hospital MindenUniversity Hospital at Ruhr University BochumGermany
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23
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Cengiz Seval G, Sahin U, Bozdag SC, Yuksel MK, Topcuoglu P, Akay BN, Sanlı HE, Gurman G, Toprak SK, Ozcan M. Allogeneic Hematopoietic Stem Cell Transplantation For Heavily Pretreated Patients With Mycosis Fungoides and Sezary Syndrome. Dermatol Ther 2022; 35:e15447. [PMID: 35289037 DOI: 10.1111/dth.15447] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 03/11/2022] [Indexed: 12/01/2022]
Abstract
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a promising strategy for treatment of heavily pretreated mycosis fungoides/Sezary syndrome (MF/SS). Herein, we aimed to evaluate the outcomes of AHSCT for heavily pretreated patients with MF/SS retrospectively. This analysis included consecutive 19 patients with MF/SS who received 20 AHSCT between 2012-2021 in our transplant center. Eight patients have been previously reported. Fifteen patients had diagnosis of MF and referred to SS in five patients. In our cohort, all cases had advanced disease (stages IIB: n = 1, IIIA: n = 7; IIIB: n = 4, IVA: n = 4, IVB: n = 3). Nine patients (47.4%) had developed large cell transformation. Only two patients received AHSCT in complete response (CR), one very good partial response (VGPR) and two partial response (PR) while the others had progressive disease (PD) (n = 15) before transplant. Seven (35%) patients were alive at the time of analysis, with a median follow up of 10.5 months (range, 0.3-113 months) after AHSCT. Nine patients (47.4%) died without disease relapse or progression. NRM was 35.9% at 1 year and 26.9% at 3 years and therafter. For all patients the probability of OS was 48.5% and 32.3% at 1- and 5- year post-transplant, respectively. AHSCT for MF/SS resulted in an estimated PFS of 45.4% at 1 year. Given the poor prognosis of patients not receiving transplants and in the absence of curative non-transplantation therapies, our results support that AHSCT is able to effectively rescue 32.3% of the population of transplant eligible, heavily pretreated patients in 5 years. This article is protected by copyright. All rights reserved.
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Affiliation(s)
| | - Ugur Sahin
- Department of Hematology, Ankara University School of Medicine
| | | | | | | | - Bengu Nisa Akay
- Department of Dermatology, Ankara University School of Medicine
| | | | - Gunhan Gurman
- Department of Hematology, Ankara University School of Medicine
| | | | - Muhit Ozcan
- Department of Hematology, Ankara University School of Medicine
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24
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Kim YH. What factors guide treatment selection in mycosis fungoides and Sezary syndrome? HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2021; 2021:303-312. [PMID: 34889422 PMCID: PMC8791145 DOI: 10.1182/hematology.2021000263] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Cutaneous T-cell lymphoma (CTCL) comprises a spectrum of T-cell lymphomas with primary skin involvement. Mycosis fungoides (MF) and Sezary syndrome (SS) are the common subtypes of CTCL in which patients present with widely diverse profiles of skin involvement and varying extents of extracutaneous disease. Patients with early-stage disease have an excellent prognosis and are managed primarily with skin-directed therapies; however, those with advanced-stage MF or SS often require multiple lines and recurrent courses of systemic therapies. Many options are available when considering systemic agents, and it is often challenging to know how to prioritize therapies to address a patient's objective disease and quality of life issues. Appreciating the disease heterogeneity and understanding the patient's overall disease profile (eg, skin, lymph nodes, blood, large cell transformation) serve as a useful framework in aligning therapies that can optimally treat active sites of disease. Tissue or blood biomarkers can be integrated into our process of prioritizing therapies and personalizing management in MF or SS. Multidisciplinary management and optimizing supportive care are additional key elements for a favorable outcome. Appropriate patients with high-risk disease should be considered for allogeneic hematopoietic stem cell transplant.
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Affiliation(s)
- Youn H. Kim
- Correspondence Youn H. Kim, Stanford University School of Medicine, 780 Welch Rd, CJ220D, C. J. Huang Bldg, Palo Alto, CA 94304; e-mail:
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25
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Franke GN, Dumann K, Jentzsch M, Monecke A, Doehring C, Nehring-Vucinic C, Schwind S, Niederwieser D, Platzbecker U, Ziemer M, Vucinic V. Case Report: Graft Versus Tumor Effect After Non-Myeloablative Allogeneic Stem-Cell Transplantation in a Patient With Brentuximab-Vedotin Refractory Sezary Syndrome. Front Oncol 2021; 11:749691. [PMID: 34956873 PMCID: PMC8695846 DOI: 10.3389/fonc.2021.749691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 11/22/2021] [Indexed: 11/13/2022] Open
Abstract
Sezary Syndrome (SS) is a rare leukemic variant of primary cutaneous T-cell lymphoma. Relapsed or refractory disease is generally considered incurable by conventional therapeutic approaches, although durable responses can be achieved with novel monoclonal antibodies. Allogeneic hematopoietic stem cell transplantation (alloHSCT) may have potential value by inducing graft vs-lymphoma (GvL) effects, but there is currently no consensus regarding the timing of alloHSCT or type of conditioning regimen. Here we present the case of a male patient who achieved a complete remission (CR) of primary refractory SS after non-myeloablative alloHSCT. Patient: Two years prior to HSCT, the patient had been refractory to CHOEP-based chemotherapy, interferon, extracorporeal photopheresis (ECP), and bexarotene. Directly prior to alloHSCT brentuximab-vedotin (BV) was applied resulting in a partial remission of the skin compartment and overall in a stable disease. Prior to HSCT, flow cytometry of the bone marrow and peripheral blood showed an infiltration with T-cells positive for CD5, CD4, low CD3, low CD2 and negative for CD7, CD38, HLA-DR and CD8. The trephine biopsy showed a 7% infiltration of SS cells. The CD4:CD8 ratio in peripheral blood (pb) was massively increased at 76.67, with 63.5% of white blood cells expressing a SS immune phenotype. The conditioning regimen included 30 mg/m2 fludarabine on days -5, -4 and -3 and total body irradiation with 2 Gy on day -1. Immunosuppression consisted of cyclosporine A from day-1 and mycophenolate mofetil from day 0. The patient received 6.55x106 CD34+ cells and 1.11x108 CD3+ cells/kg body weight. Bone marrow evaluation on day 28 still showed persistent SS cells by flow cytometry. After tapering immunosuppression until day 169, the CD4:CD8 ratio in pb normalized. CR was documented on day 169 after alloHSCT and is now ongoing for almost 3 years after alloHSCT. Conclusions: We confirm that an alloHSCT can be a curative option for refractory patients with SS. The achievement of a CR after tapering the immunosuppressive therapy indicates a significant role of the GvL effect. In present treatment algorithms for patients with SS, the timing of an alloHSCT and the intensity of conditioning should be further explored.
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Affiliation(s)
- Georg-Nikolaus Franke
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
| | | | - Madlen Jentzsch
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
| | - Astrid Monecke
- Institute for Pathology, Leipzig Medical Center, Leipzig, Germany
| | - Christine Doehring
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
| | - Claudia Nehring-Vucinic
- Department for Hematology, Internal Oncology and Gastroenterology, Asklepios Hospital Weissenfels, Weissenfels, Germany
| | - Sebastian Schwind
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
| | - Dietger Niederwieser
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
| | - Uwe Platzbecker
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
| | - Mirjana Ziemer
- Clinic for Dermatology, Leipzig Medical Center, Leipzig, Germany
| | - Vladan Vucinic
- Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig Medical Center, Leipzig, Germany
- *Correspondence: Vladan Vucinic,
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26
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Roles of OX40 and OX40 Ligand in Mycosis Fungoides and Sézary Syndrome. Int J Mol Sci 2021; 22:ijms222212576. [PMID: 34830466 PMCID: PMC8617822 DOI: 10.3390/ijms222212576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 12/03/2022] Open
Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma (CTCL), are characterized by proliferation of mature CD4+ T-helper cells. Patients with advanced-stage MF and SS have poor prognosis, with 5-year survival rates of 52%. Although a variety of systemic therapies are currently available, there are no curative options for such patients except for stem cell transplantation, and thus the treatment of advanced MF and SS still remains challenging. Therefore, elucidation of the pathophysiology of MF/SS and development of medical treatments are desired. In this study, we focused on a molecule called OX40. We examined OX40 and OX40L expression and function using clinical samples of MF and SS and CTCL cell lines. OX40 and OX40L were co-expressed on tumor cells of MF and SS. OX40 and OX40L expression was increased and correlated with disease severity markers in MF/SS patients. Anti-OX40 antibody and anti-OX40L antibody suppressed the proliferation of CTCL cell lines both in vitro and in vivo. These results suggest that OX40–OX40L interactions could contribute to the proliferation of MF/SS tumor cells and that the disruption of OX40–OX40L interactions could become a new therapeutic strategy for the treatment of MF/SS.
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Stamouli M, Gkirkas K, Karagiannidi A, Iliakis T, Chondropoulos S, Thomopoulos T, Nikolaou V, Pappa V, Papadavid E, Tsirigotis P. Allogeneic Stem Cell Transplantation with a Novel Reduced Intensity Conditioning Regimen for the Treatment of Patients with Primary Cutaneous T-cell Lymphomas. Clin Hematol Int 2021; 3:72-76. [PMID: 34595469 PMCID: PMC8432398 DOI: 10.2991/chi.k.210529.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 05/21/2021] [Indexed: 11/01/2022] Open
Abstract
The prognosis of patients with mycosis fungoides (MF) and Sezary Syndrome (SS) varies greatly, from near normal life expectancy in patients with early stage, to a median survival of less than 2 years for those diagnosed with advanced stage disease. Initial response to treatment is almost always followed by relapse and, finally, most of patients enter a phase of advanced multi-drug resistant disease with a short life expectancy after multiple lines of treatment. Allogeneic stem cell transplantation (allo-SCT) is usually limited to patients with advanced disease resistant to multiple treatments. Retrospective registry-based studies have shown increased Non-relapse Mortality (NRM) rates in patients with poor performance status, as well as in patients treated with myeloablative conditioning regimens. Another major limitation of allo-SCT is the increased relapse rate which occurs in nearly 50% of the cases, and is probably due to the fact that only heavily pretreated patients with advanced disease are referred for allo-SCT. Due to the paucity of data, the ideal conditioning regimen which will provide the maximum therapeutic benefit without the cost of increased NRM is not currently known. In this article we present our experience with a novel regimen in the treatment of patients with advanced MF/SS.
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Affiliation(s)
- Maria Stamouli
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Konstantinos Gkirkas
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Aggeliki Karagiannidi
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Theodoros Iliakis
- Hematology Division, 1st Department of Internal Medicine, Propaedeutic, LAIKON General Hospital, National and Kapodistrian University of Athens, Greece
| | - Spiros Chondropoulos
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Thomas Thomopoulos
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Vassiliki Nikolaou
- 1st Department of Dermatology, Syggros Hospital, National and Kapodistrian University of Athens, Greece
| | - Vassiliki Pappa
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Evangelia Papadavid
- 2nd Department of Dermatology, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
| | - Panagiotis Tsirigotis
- Hematology Division, 2nd Department of Internal Medicine, Propaedeutic, ATTIKON General University Hospital, National and Kapodistrian University of Athens, Greece
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Hristov AC, Tejasvi T, Wilcox RA. Cutaneous T-cell lymphomas: 2021 update on diagnosis, risk-stratification, and management. Am J Hematol 2021; 96:1313-1328. [PMID: 34297414 PMCID: PMC8486344 DOI: 10.1002/ajh.26299] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 11/08/2022]
Abstract
DISEASE OVERVIEW Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). DIAGNOSIS The diagnosis of MF or SS requires the integration of clinical and histopathologic data. RISK-ADAPTED THERAPY TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multi-disciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.
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Affiliation(s)
- Alexandra C. Hristov
- Departments of Pathology and Dermatology, North Campus Research Complex, Ann Arbor, Michigan, USA
| | - Trilokraj Tejasvi
- Director Cutaneous Lymphoma program, Department of Dermatology, A. Alfred Taubman Health Care Center, Ann Arbor, Michigan, USA
| | - Ryan A. Wilcox
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, USA
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Abstract
Primary cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. CTCL subtypes demonstrate a variety of clinical, histological, and molecular features, and can follow an indolent or a very aggressive course. The underlying pathogenetic mechanisms are not yet entirely understood. The pathophysiology of CTCL is complex and a single initiating factor has not yet been identified. Diagnosis is based on clinicopathological correlation and requires an interdisciplinary team. Treatment decision is made based on short-term and long-term goals. Therapy options comprise skin-directed therapies, such as topical steroids or phototherapy, and systemic therapies, such as monoclonal antibodies or chemotherapy. So far, the only curative treatment approach is allogeneic haematopoietic stem cell transplantation. Novel therapies, such as chimeric antigen receptor T cells, monoclonal antibodies or small molecules, are being investigated in clinical trials. Patients with CTCL have reduced quality of life and a lack of effective treatment options. Further research is needed to better identify the underlying mechanisms of CTCL development and course as well as to better tailor treatment strategies to individual patients.
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Xu S, Foss F. New nonchemotherapy treatment options for cutaneous T-cell lymphomas. Expert Rev Anticancer Ther 2021; 21:1017-1028. [PMID: 33554707 DOI: 10.1080/14737140.2021.1882859] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches. AREAS COVERED In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors. EXPERT OPINION Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future.
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Affiliation(s)
- Suzanne Xu
- Yale University School of Medicine, New Haven, United States
| | - Francine Foss
- Hematology and Stem Cell Transplantation, Yale University School of Medicine, New Haven, United States
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31
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Mehta-Shah N, Horwitz SM, Ansell S, Ai WZ, Barnes J, Barta SK, Clemens MW, Dogan A, Fisher K, Goodman AM, Goyal G, Guitart J, Halwani A, Haverkos BM, Hoppe RT, Jacobsen E, Jagadeesh D, Lunning MA, Mehta A, Olsen EA, Pro B, Rajguru SA, Shanbhag S, Shaver A, Shustov A, Sokol L, Torka P, Torres-Cabala C, Wilcox R, William BM, Zain J, Dwyer MA, Sundar H, Kim YH. NCCN Guidelines Insights: Primary Cutaneous Lymphomas, Version 2.2020. J Natl Compr Canc Netw 2021; 18:522-536. [PMID: 32380458 DOI: 10.6004/jnccn.2020.0022] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
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Affiliation(s)
- Neha Mehta-Shah
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - Weiyun Z Ai
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | - Stefan K Barta
- Abramson Cancer Center at the University of Pennsylvania
| | | | | | - Kristopher Fisher
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | | | | | - Joan Guitart
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | | | - Deepa Jagadeesh
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | - Barbara Pro
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - Satish Shanbhag
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | - Andrei Shustov
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | | | - Basem M William
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
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Hernández-Coronado M, Gómez-Almaguer D, Jaime-Pérez JC. Haploidentical hematopoietic cell transplantation for mycosis fungoides/ Sezary syndrome using reduced intensity conditioning after brentuximab therapy discontinuation: advantages of an outpatient program in the times of COVID-19. Hematol Transfus Cell Ther 2021; 43:357-360. [PMID: 34253503 PMCID: PMC8446262 DOI: 10.1016/j.htct.2021.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 05/17/2021] [Indexed: 11/25/2022] Open
Affiliation(s)
- Marcela Hernández-Coronado
- Dr. José E. González University Hospital and School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
| | - David Gómez-Almaguer
- Dr. José E. González University Hospital and School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
| | - José Carlos Jaime-Pérez
- Dr. José E. González University Hospital and School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.
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Sethi TK, Montanari F, Foss F, Reddy N. How we treat advanced stage cutaneous T-cell lymphoma - mycosis fungoides and Sézary syndrome. Br J Haematol 2021; 195:352-364. [PMID: 33987825 DOI: 10.1111/bjh.17458] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
T-cell lymphomas (TCLs) constitute a rare subset of non-Hodgkin lymphomas, with mycosis fungoides/Sézary syndrome (MF/SS) being the most common subtype of cutaneous TCLs (CTCLs). Considered an incurable but treatable disease, MF/SS management presents several challenges including diagnostic delays, debilitating effect on patients' quality of life, need for several lines of therapies, multidisciplinary care and cumulative drug toxicities limiting duration of use. The present review intends to provide an overview of the recent advances in our understanding of the biology of CTCL and how these are being leveraged to provide additional treatment options for management of advanced and recurrent disease. In addition, the discussion of the different modalities of treatment is summarised to further outline the importance of multidisciplinary care and early referral to CTCL centres.
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Affiliation(s)
- Tarsheen K Sethi
- Division of Hematology, Yale University School of Medicine, New Haven, CT, USA
| | - Francesca Montanari
- Division of Hematology, Yale University School of Medicine, New Haven, CT, USA
| | - Francine Foss
- Division of Hematology, Yale University School of Medicine, New Haven, CT, USA
| | - Nishitha Reddy
- Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
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Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood Adv 2021; 4:4474-4482. [PMID: 32941647 DOI: 10.1182/bloodadvances.2020001627] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 08/13/2020] [Indexed: 02/08/2023] Open
Abstract
The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.
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35
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Boo YL, Koh LP. Hematopoietic Stem Cell Transplantation in T Cell and Natural Killer Cell Lymphomas: Update on Recent Advances. Transplant Cell Ther 2021; 27:571-588. [PMID: 33857661 DOI: 10.1016/j.jtct.2021.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 11/19/2022]
Abstract
Mature T and natural killer (NK) cell non-Hodgkin lymphoma (T-NHL) has a poor prognosis. Data from existing retrospective and prospective studies have suggested that high-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) may improve the survival in patients with chemosensitive disease, either in the upfront or salvage setting. Auto-HCT is currently recommended to be used as frontline consolidation in peripheral T cell lymphoma not otherwise specified, angioimmunoblastic T cell lymphoma, anaplastic large cell lymphoma-anaplastic lymphoma kinase negative, NK/T cell (disseminated), and enteropathy-associated T cell lymphoma. However, about one-third of patients never reach transplantation because of early relapse or refractory disease. Allogeneic hematopoietic cell transplantation (allo-HCT), via its immunologic graft-versus-lymphoma effect, has been used to salvage patients with relapsed or refractory disease, resulting in long-term disease-free survival in a fraction of patients. However, the higher risk of transplant-related mortality due to regimen-related toxicities, graft-versus-host disease, and post-transplant infectious complications continues to limit the mainstream adoption of allo-HCT for this disease. Despite that, allo-HCT has been incorporated as part of the frontline treatment for aggressive subtypes of T-NHL, such as γδ T cell lymphoma and aggressive NK cell leukemia. Recent attempts to incorporate novel targeted T cell directed therapies into the treatment pathway of T-NHL may enhance treatment response and enable more patients to reach transplant, offering an alternative means of treating this disease.
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Affiliation(s)
- Yang Liang Boo
- Department of Hematology-Oncology, National University Cancer Institute, Singapore; Department of Hematology, Hospital Sultanah Aminah, Johor Bahru, Malaysia
| | - Liang Piu Koh
- Department of Hematology-Oncology, National University Cancer Institute, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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36
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Howles A, Scarisbrick J. Cutaneous T-cell lymphoma: practical recommendations to enhance clinical practice. Br J Hosp Med (Lond) 2021; 82:1-6. [PMID: 33792384 DOI: 10.12968/hmed.2021.0055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Management of cutaneous T-cell lymphoma should provide a holistic approach to a patient's wellbeing. Treatments depend on the stage of lymphoma. Patients with the early stages tend to have a near-normal life expectancy. Management should be aimed at improving the extent of disease and reducing symptoms with minimal therapeutic adverse effects. Skin-directed treatments are preferred and may be used in combination with treatments for symptom relief such as anti-pruritic medication. In advanced stages of disease where the median life expectancy is reduced the aims are also to prevent disease progression and prolong life, and this requires a multidisciplinary approach. Symptom control remains important as patients often have painful, itchy disfiguring lesions which greatly impact on health-related quality of life. National and international guidelines provide stage-related treatment options to be considered with first-line options followed by subsequent second-line therapies. All are listed in no particular order of preference and are chosen according to patients' needs and expertise of the treating centre. Several first-line options may be chosen before moving to the second-line options. Three drugs received European Medicines Agency approval in 2017 and 2018 (chlormethine gel, brentuximab and mogamulizumab) but there still remains an unmet need for more improved treatments or combinations. Most treatments only result in a partial response and there is no cure for early-stage disease; as such, patients live for a long time with their disease. In the advanced stages if a good response is achieved eligible patients will be considered for an allogeneic haematopoietic stem cell transplant.
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Affiliation(s)
- Allison Howles
- Skin Lymphoma Group, University Hospital Birmingham, Birmingham, UK
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37
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Allogeneic haematopoietic stem cell transplantation for advanced stage mycosis fungoides and Sézary syndrome: never-late, never-never? Bone Marrow Transplant 2021; 56:1232-1234. [PMID: 33526916 DOI: 10.1038/s41409-020-01150-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 10/26/2020] [Accepted: 11/10/2020] [Indexed: 11/09/2022]
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38
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Domingo-Domenech E, Duarte RF, Boumedil A, Onida F, Gabriel I, Finel H, Arcese W, Browne P, Beelen D, Kobbe G, Veelken H, Arranz R, Greinix H, Lenhoff S, Poiré X, Ribera JM, Thompson J, Zuckerman T, Mufti GJ, Cortelezzi A, Olavarria E, Dreger P, Sureda A, Montoto S. Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides and Sézary syndrome. An updated experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2021; 56:1391-1401. [PMID: 33420392 DOI: 10.1038/s41409-020-01197-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 10/05/2020] [Accepted: 12/09/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD). METHODS AND PATIENTS Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported. RESULTS 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS. CONCLUSIONS This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.
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Affiliation(s)
- E Domingo-Domenech
- Hematology Department, Institut Català d'Oncologia. Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
| | - R F Duarte
- Hematology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - A Boumedil
- EBMT Central Registry Office, Paris, France
| | - F Onida
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico IRCCS, Milano, Italy
| | - I Gabriel
- Department of Hematology, Imperial College, Hammersmith Hospital, London, United Kingdom
| | - H Finel
- EBMT Central Registry Office, Paris, France
| | - W Arcese
- Tor Vergata University of Rome, Stem Cell Transplant Unit, Policlinico Universitario Tor Vergata, Rome, Italy
| | - P Browne
- St's James Hospital, Dublin, Ireland
| | - D Beelen
- University Hospital, Department of Bone Marrow Transplantation, Essen, Germany
| | - G Kobbe
- Heinrich Heine University, Medical F, Department of Hematology, Düsseldorf, Germany
| | - H Veelken
- Leiden University Medical Center, Leiden, The Netherlands
| | - R Arranz
- Hematology Department, Hospital La Princesa, Madrid, Spain
| | - H Greinix
- Division of Hematology, Medical University Graz, Graz, Austria
| | - S Lenhoff
- Skanes University Hospital, Department of Hematology, Lund, Sweden
| | - X Poiré
- Cliniques Universitaires St. Luc, Department of Hematology, Brussels, Belgium
| | - J M Ribera
- Hematology Department, Institut Català d'Oncologia, Josep Carreras Leukemia Research Institute, Badalona, Spain
| | - J Thompson
- Albert's Stem Cell Transplantation Center, Pretoria, South Africa
| | - T Zuckerman
- Ramban Medical Center, Department of Hematology and Bone Marrow Transplantation, Haifa, Israel
| | - G J Mufti
- GKT School of Medicine, Dept. of Haematological Medicine, King's Denmark Hill Campus, London, United Kingdom
| | - A Cortelezzi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico IRCCS, Milano, Italy
| | - E Olavarria
- Department of Hematology, Imperial College, Hammersmith Hospital, London, United Kingdom
| | - P Dreger
- Universitaetsklinkum Heidelberg, Heidelberg, Germany
| | - A Sureda
- Hematology Department, Institut Català d'Oncologia. Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Barcelona, Spain
| | - S Montoto
- Department of Haemato-Oncology, St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
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Kamijo H, Miyagaki T. Mycosis Fungoides and Sézary Syndrome: Updates and Review of Current Therapy. Curr Treat Options Oncol 2021; 22:10. [PMID: 33415447 DOI: 10.1007/s11864-020-00809-w] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 12/12/2022]
Abstract
OPINION STATEMENT While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a median survival of less than 5 years. Although there are a number of treatments currently available, achieving and maintaining a durable response remain challenging, especially in advanced-stage MF/SS. The choice of frontline therapy is dependent on the stage of disease. For early-stage MF, the treatment concept is to control skin lesions mainly by skin-directed therapies, such as topical therapies, phototherapies, and radiotherapies. For advanced-stage MF/SS, systemic treatments by biological or targeted therapies including bexarotene and interferon either alone or in combination are tried first, with more immunosuppressive chemotherapies being reserved for refractory or rapidly progressive disease. Recent improvements in biological or targeted therapies include brentuximab vedotin and mogamulizumab. When biopsy samples have 10% or more CD30-positive malignant cells, brentuximab vedotin, an anti-CD30 antibody conjugated to monomethyl auristin E, can be a desirable treatment option. For cases with blood involvement, mogamulizumab, an antibody binding to C-C chemokine receptor 4, is effective with high response rates. In the refractory setting, alemtuzumab, histone deacetylase inhibitors, pralatrexate, gemcitabine, and doxorubicin are considered as the treatment option. Because only allogeneic hematopoietic stem cell transplantation can offer a chance of cure with durable complete remission, advanced-stage patients with a markedly short life expectancy should be evaluated for eligibility. Given that there are few randomized controlled studies in the literature, it is necessary to investigate which therapy is preferable for each patient with MF/SS by comparative prospective trials.
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Affiliation(s)
- Hiroaki Kamijo
- Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tomomitsu Miyagaki
- Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
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Bhabha FK, McCormack C, Wells J, Campbell BA, Newland K, Lade S, Buelens O, Joske D, Shortt J, Mapp S, Radeski D, Hertzberg M, Khot A, Van Der Weyden C, Khoo C, Hawkes E, Prince HM. Mycosis fungoides and Sézary syndrome: Australian clinical practice statement. Australas J Dermatol 2020; 62:e8-e18. [PMID: 33368169 DOI: 10.1111/ajd.13467] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/16/2020] [Accepted: 08/17/2020] [Indexed: 11/28/2022]
Abstract
Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).
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Affiliation(s)
- Friyana K Bhabha
- Department of Dermatology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Christopher McCormack
- Department of Dermatology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Jillian Wells
- Department of Dermatology, Westmead Hospital and The University of Sydney, Sydney, New South Wales, Australia
| | - Belinda A Campbell
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia
| | - Kate Newland
- Department of Dermatology, Flinders Medical Centre, Bedford Park, South Australia, Australia.,Department of Dermatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Stephen Lade
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Odette Buelens
- Nurse Practitioner, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - David Joske
- Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Jake Shortt
- School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia.,Department of Haematology, Monash Health, Clayton, Victoria, Australia
| | - Sally Mapp
- Haematology Department, Princess Alexandra Hospital, Brisbane, Australia
| | - Dejan Radeski
- Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Mark Hertzberg
- Department of Haematology, Prince of Wales Hospital, Randwick, Australia
| | - Amit Khot
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Carrie Van Der Weyden
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Christine Khoo
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Eliza Hawkes
- Olivia Newton-John Cancer Research Institute at Austin Health, Heidelberg, Victoria, Australia.,Eastern Health, Box Hill, Victoria, Australia.,University of Melbourne, Melbourne, Victoria, Australia
| | - H Miles Prince
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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41
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Ohtsuka M, Hamada T, Miyagaki T, Shimauchi T, Yonekura K, Kiyohara E, Fujita H, Izutsu K, Okuma K, Kawai K, Koga H, Sugaya M. Outlines of the Japanese guidelines for the management of primary cutaneous lymphomas 2020. J Dermatol 2020; 48:e49-e71. [PMID: 33245165 DOI: 10.1111/1346-8138.15707] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 10/31/2020] [Indexed: 01/06/2023]
Abstract
Since the publication of the Japanese "Guidelines for the management of cutaneous lymphomas" in 2011, the World Health Organization (WHO) classification of hematolymphoid neoplasms and the WHO-European Organisation for Research and Treatment of Cancer classification for primary cutaneous lymphomas were updated and a number of novel systemic drugs for cutaneous T-cell lymphoma had been approved in Japan. In 2020, we revised the Japanese guidelines for the management of cutaneous lymphomas with consideration of the recent advances in the understanding of the pathophysiology and classification of cutaneous lymphomas together with the update of treatment strategies reflecting the advent of novel drugs. In addition to a brief explanation of epidemiology, diagnosis, staging system, prognosis and management of each subtype of cutaneous lymphomas, the recommendations for nine clinical questions regarding treatment options that can vary even among experts are also described. A systematic review process and determination of recommendations in answer to each clinical question have been performed in accordance with the Grading of Recommendations, Assessment, Development and Evaluation scheme by a multidisciplinary expert panel consisting of dermatologists, a hematologist and a radiation oncologist. In this article, we present the outlines of the revised Japanese "Guidelines for the management of cutaneous lymphomas".
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Affiliation(s)
- Mikio Ohtsuka
- Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Toshihisa Hamada
- Department of Dermatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Tomomitsu Miyagaki
- Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Takatoshi Shimauchi
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kentaro Yonekura
- Department of Dermatology, Imamura General Hospital, Kagoshima, Japan
| | - Eiji Kiyohara
- Department of Dermatology, Osaka University School of Medicine, Suita, Japan
| | - Hideki Fujita
- Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Koji Izutsu
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Kae Okuma
- Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuhiro Kawai
- Department of Dermatology, Kido Hospital, Niigata, Japan
| | - Hiroshi Koga
- Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Makoto Sugaya
- Department of Dermatology, International University of Health and Welfare, Narita, Japan
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42
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Kudelka MR, Switchenko JM, Lechowicz MJ, Esiashvili N, Flowers CR, Khan MK, Allen PB. Maintenance Therapy for Cutaneous T-cell Lymphoma After Total Skin Electron Irradiation: Evidence for Improved Overall Survival With Ultraviolet Therapy. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2020; 20:757-767.e3. [PMID: 32703750 PMCID: PMC9126313 DOI: 10.1016/j.clml.2020.06.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/11/2020] [Accepted: 06/24/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Treatment of cutaneous T-cell lymphoma (CTCL) with total skin electron beam (TSEB) therapy has been associated with deep responses but short progression-free intervals. Maintenance therapy might prolong the response duration; however, limited data assessing the outcomes with maintenance therapy after TSEB are available. We evaluated the effect of maintenance therapy on the outcomes for patients with CTCL receiving TSEB therapy. MATERIALS AND METHODS We conducted a single-center retrospective analysis of 101 patients with CTCL who had received TSEB therapy from 1998 to 2018 at the Winship Cancer Institute of Emory University and compared the overall survival (OS) and progression-free survival (PFS) for patients had received maintenance therapy, including retinoids, interferon, ultraviolet therapy, nitrogen mustard, and extracorporeal photopheresis compared with those who had not. RESULTS We found that pooled maintenance therapies improved PFS (hazard ratio [HR], 0.60; P = .026) but not OS (median HR, 0.73; P = .264). The median PFS and OS was 7.2 months versus 9.6 months and 2.4 years versus 4.2 years for the no maintenance and maintenance groups, respectively. On exploratory analysis of the individual regimens, ultraviolet therapy was associated with improved OS (HR, 0.21; P = .034) and PFS (HR, 0.26; P = .002) compared with no maintenance. CONCLUSION Among the patients with CTCL who had received TSEB therapy, maintenance therapy improved PFS for all patients, and ultraviolet-based maintenance improved both PFS and OS in a subset of patients.
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Affiliation(s)
- Matthew R Kudelka
- Medical Scientist Training Program, Emory School of Medicine, Atlanta, GA
| | - Jeffrey M Switchenko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA
| | | | - Natia Esiashvili
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | | | - Mohammad K Khan
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Pamela B Allen
- Winship Cancer Institute of Emory University, Atlanta, GA.
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43
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Scarisbrick JJ, Bagot M, Ortiz-Romero PL. The changing therapeutic landscape, burden of disease, and unmet needs in patients with cutaneous T-cell lymphoma. Br J Haematol 2020; 192:683-696. [PMID: 33095448 PMCID: PMC7894136 DOI: 10.1111/bjh.17117] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 08/31/2020] [Indexed: 12/18/2022]
Abstract
Cutaneous T-cell lymphomas (CTCLs) have a chronic, relapsing course, and the most common subtypes are mycosis fungoides and Sézary syndrome. The disease causes visible skin alterations and can also cause alopecia, pruritus and pain, all of which can impact patients' health-related quality of life (HRQoL). The goal of treatment is to reduce symptoms and prevent disease progression. However, treatment recommendations are often based on low levels of evidence due to the lack of well-designed randomised clinical trials and treatment guidelines, and approved drugs vary considerably across different countries and regions. Currently, available treatments rarely lead to durable remissions and eventually become less effective, meaning patients often require multiple therapy changes. Skin-directed therapies (SDTs) are first-line treatments for early-stage CTCL, whereas systemic therapies may be needed for early-stage disease that does not respond to SDT or for advanced-stage disease. However, patients can experience significant side-effects with these treatments or may be unable to tolerate them. Hence, there is an unmet need for effective therapies with good safety profiles for the treatment of early- and late-stage CTCL. Here, we review current treatment guidelines, investigational and approved treatments, the impact of CTCL on patients' HRQoL, and the treatment of pruritus.
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Affiliation(s)
| | - Martine Bagot
- Hôpital Saint Louis, Université de Paris, Paris, France
| | - Pablo L Ortiz-Romero
- Department of Dermatology, University Complutense, Hospital 12 de Octubre, Medical School, Institute i+12, Madrid, Spain
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44
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Allogeneic Hematopoietic Stem Cell Transplantation in Cutaneous T-Cell Lymphomas. Cancers (Basel) 2020; 12:cancers12102856. [PMID: 33023002 PMCID: PMC7601655 DOI: 10.3390/cancers12102856] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/30/2020] [Accepted: 10/01/2020] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Advanced-stage cutaneous T-cell lymphomas are aggressive diseases with frequent disease relapses and a reduced overall survival. Most treatment regimens fail to induce long-term remissions. Allogeneic hematopoietic stem cell transplantation has been associated with treatment-free long-term remissions and holds a potential for cure in this disease but is associated with frequent complications, mostly linked to the development of graft-versus-host disease and infections. Herein, we review the current evidence supporting the use of allogeneic stem cell transplantation in advanced-stage cutaneous T-cell lymphomas. Abstract Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that develop primarily in the skin. They account for almost 80% of primary cutaneous lymphomas. Epidermotropic CTCLs (mycosis fungoides (MF) and Sézary syndrome (SS)) are the most common form of CTCL. The course of the disease ranges from an indolent clinical behavior in early-stage disease to an aggressive evolution in the advanced stages. Advanced-stage disease is defined by the presence of tumors, erythroderma, or significant blood, nodal or visceral involvement. Advanced-stage disease is characterized by frequent disease relapses, refractory disease, a severely impaired quality of life and reduced overall survival. In the last twenty-five years, allogeneic hematopoietic stem cell transplantation (HSCT) has led to prolonged remissions in advanced CTCL, presumably linked to a graft-versus-lymphoma effect and is thus emerging as a potential cure of the disease. However, the high post-transplant relapse rate and severe morbidity and mortality associated with graft-versus-host disease and infections are important issues. Allogeneic HSCT is thus mostly considered in young patients with no comorbidities and an aggressive, advanced-stage CTCL. Allogeneic HSCT gives the best results in patients with a pre-transplant complete remission of the lymphoma. For this reason, one of the challenges is to define the best time to consider allogeneic HSCT in the disease course. Early identification of patients at high risk for progression is important to identify candidates who may benefit from allogeneic HSCT before their disease becomes treatment-refractory. This review describes the role of allogeneic HSCT in CTCL, summarizes the published data and future perspectives in this area.
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45
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Kanda-Kato M, Yoshioka S, Ishikawa T. Haploidentical Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide for Sézary Syndrome. Case Rep Oncol 2020; 13:1053-1058. [PMID: 33082748 PMCID: PMC7548877 DOI: 10.1159/000509347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 06/09/2020] [Indexed: 01/01/2023] Open
Abstract
Patients with advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment option; however, since most patients with MF/SS are elderly, they often have difficulty in finding HLA-matched donors. In recent years, HCT from HLA-haploidentical donors (haplo-HCT) using posttransplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis has been conducted for patients without HLA-matched donors. Infectious complications, particularly cutaneous bacterial infections, are common among patients with MF/SS. The lower incidence of severe infectious complications after haplo-HCT than after an unrelated cord blood transplantation could lead to lower transplant-related mortality. Here, we report on a patient with SS who was treated successfully with haplo-HCT with PTCy. The patient has remained in complete remission for more than 24 months.
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Affiliation(s)
- Madoka Kanda-Kato
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Satoshi Yoshioka
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Takayuki Ishikawa
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
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46
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Dimitriou F, Schanz U, Nair G, Kimeswenger S, Brüggen MC, Hoetzenecker W, French LE, Dummer R, Cozzio A, Guenova E. Long-Term Disease Control After Allogeneic Hematopoietic Stem Cell Transplantation in Primary Cutaneous T-Cell Lymphoma; Results From a Single Institution Analysis. Front Med (Lausanne) 2020; 7:290. [PMID: 32714935 PMCID: PMC7344271 DOI: 10.3389/fmed.2020.00290] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 05/22/2020] [Indexed: 12/22/2022] Open
Abstract
Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been proposed as curative approach for advanced cutaneous T–cell lymphomas (CTCL). Currently, there is no established consensus for the management of disease relapse after alloHSCT. Results: Ten patients, previously treated with multiple lines of systemic treatment, received alloHSCT. Six patients had achieved partial response (PR, N = 5) and complete response (CR, N = 1) prior to HSCT. Post—HSCT, seven patients (N = 7) relapsed after a median time of 3.3 months (0.5–7.4 months) and were subsequently treated with radiotherapy (RT, N = 1), RT and adoptive T-cell transfer with EBV specific cells (N = 1), R-CHOP (N = 1) and interferon alpha−2a combined either with donor lymphocyte infusion (N = 1) or with brentuximab—vedotin (N = 1). One patient (N = 1) achieved PR only after reducing the immunosuppression. Two patients relapsed again and received interferon alpha−2a and brentuximab—vedotin, respectively. After a median follow-up time of 12.6 months (3.5–73.7 months) six patients were alive (60%) and four had deceased, three (N = 3) due to CTCL and one (N = 1) due to GVHD. Conclusion: Disease relapse after alloHSCT can be controlled with available treatments. For most patients who ultimately relapsed, reduction of immunosuppression and interferon alpha−2a either administered alone or in combination with another systemic agent were preferred. Although interferon alpha−2a, similarly to immunosuppression reduction, may be beneficial for the achievement of graft–vs.–lymphoma effect, the risk of simultaneous worsening of GVHD must be carefully evaluated and taken into consideration.
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Affiliation(s)
- Florentia Dimitriou
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Urs Schanz
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.,Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
| | - Gayathri Nair
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.,Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
| | - Susanne Kimeswenger
- Department of Dermatology, Kepler University Hospital Linz, Linz, Austria.,Department of Soft Matter Physics, Institute for Experimental Physics, Johannes Kepler University, Linz, Austria
| | - Marie-Charlotte Brüggen
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | | | - Lars E French
- Department of Dermatology, University Hospital Munich (LMU), Munich, Germany
| | - Reinhard Dummer
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Antonio Cozzio
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.,Department of Dermatology, Kantonsspital St Gallen, St Gallen, Switzerland
| | - Emmanuella Guenova
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.,Faculty of Medicine, University of Zurich, Zurich, Switzerland.,Lausanne University Hospital (CHUV) and Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
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47
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Isufi I, Seropian S, Gowda L, Wilson LD, Roberts K, Girardi M, Perreault S, Foss F. Outcomes for allogeneic stem cell transplantation in refractory mycosis fungoides and primary cutaneous gamma Delta T cell lymphomas. Leuk Lymphoma 2020; 61:2955-2961. [DOI: 10.1080/10428194.2020.1790555] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Iris Isufi
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Stuart Seropian
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Lohith Gowda
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Lynn D. Wilson
- Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Kenneth Roberts
- Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Michael Girardi
- Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
| | - Sarah Perreault
- Department of Pharmacy, Yale New Haven Hospital, New Haven, CT, USA
| | - Francine Foss
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
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48
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Mori T, Shiratori S, Suzumiya J, Kurokawa M, Shindo M, Naoyuki U, Katsuto T, Miyamoto T, Morishige S, Hirokawa M, Fukuda T, Atsuta Y, Suzuki R. Outcome of allogeneic hematopoietic stem cell transplantation for mycosis fungoides and Sézary syndrome. Hematol Oncol 2020; 38:266-271. [PMID: 32011008 DOI: 10.1002/hon.2719] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 12/31/2019] [Accepted: 01/12/2020] [Indexed: 11/05/2022]
Abstract
Although allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to provide prolonged remission of relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS), its role has not been fully evaluated. Here, the outcomes of allogeneic HSCT for patients with MF/SS were retrospectively evaluated by using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Forty-eight patients were evaluable and enrolled in the analysis. Median age was 45.5 years. Eighteen patients (38%) received myeloablative conditioning, and 33 (69%) received HSCT from an alternative donor. Disease status was complete or partial response in 25% of the patients and relapsed or refractory in the others. At the time of analysis, 18 patients were alive, with a median follow-up of 31.0 months (range, 3.8-31.1). Three-year overall survival (OS) and progression-free survival (PFS) were 30% (95%CI, 16-45%) and 19% (95%CI, 9-31%), respectively. Disease progression was not observed later than 17 months after transplantation. Both disease status and performance status at transplant significantly affected OS and PFS. Although our findings suggest that allogeneic HSCT provides long-term PFS in patients with MF/SS, the timing of transplantation should be decided carefully based on the disease status and the patient's condition in order to improve the outcome.
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Affiliation(s)
- Takehiko Mori
- Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Souichi Shiratori
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Junji Suzumiya
- Department of Oncology/Hematology, School of Medicine, Shimane University, Shimane, Japan
| | - Mineo Kurokawa
- Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Motohiro Shindo
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Uchida Naoyuki
- Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan
| | - Takenaka Katsuto
- First Department of Internal Medicine, Ehime University Hospital, Ehime, Japan
| | - Toshihiro Miyamoto
- Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Satoshi Morishige
- Division of Hematology and Oncology, Department of Medicine, Kurume University Hospital, Kurume, Japan
| | - Makoto Hirokawa
- Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
| | - Takahiro Fukuda
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.,Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ritsuro Suzuki
- Department of Oncology/Hematology, School of Medicine, Shimane University, Shimane, Japan
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49
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Dalal M, Mitchell S, McCloskey C, Zagadailov E, Gautam A. The clinical and humanistic burden of cutaneous T-cell lymphomas and response to conventional and novel therapies: results of a systematic review. Expert Rev Hematol 2020; 13:405-419. [DOI: 10.1080/17474086.2020.1717945] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Mehul Dalal
- Global Outcomes Research, Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA
| | | | | | - Erin Zagadailov
- Global Outcomes Research, Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA
| | - Ashish Gautam
- Global Outcomes Research, Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA
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50
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Iqbal M, Reljic T, Ayala E, Sher T, Murthy H, Roy V, Foran J, Tun H, Kumar A, Kharfan-Dabaja MA. Efficacy of Allogeneic Hematopoietic Cell Transplantation in Cutaneous T Cell Lymphoma: Results of a Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant 2020; 26:76-82. [DOI: 10.1016/j.bbmt.2019.08.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 08/23/2019] [Accepted: 08/25/2019] [Indexed: 11/25/2022]
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