Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Allogeneic stem cell transplantation; Peripheral T cell lymphoma; Retrospective analysis
Abstract :
[en] Background: Peripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated.
Methods: We retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplantrelated mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014.
Results: AlloSCT was given as part of front-line therapy (n = 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy (n = 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years.
TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III–IV acute GvHD (HR = 2.57, 95% CI 1.53–4.31; p = 0.00036), low Karnofsky score < 80% (HR = 5.14, 95% CI 2.02–13.06; p = 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25–3.89; p = 0.0062) were significantly associated with a reduced OS.
Conclusions: The data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients.
Disciplines :
Hematology
Author, co-author :
Mamez, Anne-Claire
Dupont, Axelle
Blaise, Didier
Chavallier, Patrice
Forcade, Edouard
Ceballos, Patrice
Mohty, Mohamad
Suarez, Felipe
BEGUIN, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'hématologie clinique
Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: Pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124-30.
Abouyabis AN, Shenoy PJ, Sinha R, et al. A systematic review and meta-analysis of front-line anthracycline-based chemotherapy regimens for peripheral T-cell lymphoma. ISRN Hematol. 2011;623924:16.
Schmitz N, de Leval L. How I manage peripheral T-cell lymphoma, not otherwise specified and angioimmunoblastic T-cell lymphoma: Current practice and a glimpse into the future. Br J Haematol. 2017;176:851-66.
Mak V, Hamm J, Chhanabhai M, et al. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: Spectrum of disease and rare long-term survivors. J Clin Oncol. 2013;31:1970-6.
Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30:631-6.
Lamarque M, Bossard C, Contejean A, et al. Brentuximab vedotin in refractory or relapsed peripheral T-cell lymphomas: The French named patient program experience in 56 patients. Haematologica. 2016 Mar;101(3):e103-6. https://doi.org/10.3324/haematol.2015.135400 Epub 2015 Dec 24.
Gauthier J, Chantepie S, Bouabdallah K, et al. Allogeneic hematopoietic cell transplantation for Hodgkin's disease, mantle cell lymphoma and other rare entities: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Bull Cancer. 2017;104:S112-20.
Kharfan-Dabaja MA, Kumar A, Ayala E, et al. Clinical practice recommendations on indication and timing of hematopoietic cell transplantation in mature T cell and NK/T cell lymphomas: An international collaborative effort on behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2017;23:1826-38.
Fossard G, Broussais F, Coelho I, et al. Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: An analysis of patients from LYSA centers. Ann Oncol. 2018;29:715-23.
Park SI, Horwitz SM, Foss FM, et al. The role of autologous stem cell transplantation in patients with nodal peripheral T-cell lymphomas in first complete remission: Report from COMPLETE, a prospective, multicenter cohort study. Cancer. 2019;29:31861.
Reimer P, Rudiger T, Geissinger E, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: Results of a prospective multicenter study. J Clin Oncol. 2009;27:106-13.
Alcantara M, Tesio M, June CH, et al. CAR T-cells for T-cell malignancies: Challenges in distinguishing between therapeutic, normal, and neoplastic T-cells. Leukemia. 2018;32:2307-15.
Mamez AC, Souchet L, Roos-Weil D, et al. Graft-versus-T-cell lymphoma effect: A sustained CR after tapering immunosuppressive drugs in a patient with angioimmunoblastic T-cell lymphoma in relapse after allogeneic transplantation. Bone Marrow Transplant. 2015;50:304-6.
Le Gouill S, Milpied N, Buzyn A, et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: A study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol. 2008;26:2264-71.
Corradini P, Dodero A, Zallio F, et al. Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol. 2004;22:2172-6.
Mamez AC, Levy V, Chevallier P, et al. Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: A study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). Bone Marrow Transplant. 2016;51:358-64.
Kanakry JA, Kasamon YL, Gocke CD, et al. Outcomes of related donor HLA-identical or HLA-haploidentical allogeneic blood or marrow transplantation for peripheral T cell lymphoma. Biol Blood Marrow Transplant. 2013;19:602-6.
Przepiorka D, Weisdorf D, Martin P, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825-8.
Smith SM, Burns LJ, van Besien K, et al. Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. J Clin Oncol. 2013;31:3100-9.
d'Amore F, Gaulard P, Trumper L, et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;108.
El-Asmar J, Reljic T, Ayala E, et al. Efficacy of high-dose therapy and autologous hematopoietic cell transplantation in peripheral T cell lymphomas as front-line consolidation or in the relapsed/refractory setting: A systematic review/meta-analysis. Biol Blood Marrow Transplant. 2016;22:802-14.
Loirat M, Chevallier P, Leux C, et al. Upfront allogeneic stem-cell transplantation for patients with nonlocalized untreated peripheral T-cell lymphoma: An intention-to-treat analysis from a single center. Ann Oncol. 2015;26:386-92.
Corradini P, Vitolo U, Rambaldi A, et al. Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma. Leukemia. 2014;28:1885-91.
Mercadal S, Briones J, Xicoy B, et al. Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma. Ann Oncol. 2008;19:958-63.
Shmitz N, Truemper L, Ziepert M, et al. First-line therapy of T-cell lymphoma: Allogeneic or autologous transplantation for consolidation-final results of the AATT study. J Clin Oncol. 2019;37:7503-3.
Zain J, Palmer JM, Delioukina M, et al. Allogeneic hematopoietic cell transplant for peripheral T-cell non-Hodgkin lymphoma results in long-term disease control. Leuk Lymphoma. 2011;52:1463-73.
Kyriakou C, Canals C, Finke J, et al. Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: A retrospective study from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2009;27:3951-8.
Jacobsen ED, Kim HT, Ho VT, et al. A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome. Ann Oncol. 2011;22:1608-13.
Goldberg JD, Chou JF, Horwitz S, et al. Long-term survival in patients with peripheral T-cell non-Hodgkin lymphomas after allogeneic hematopoietic stem cell transplant. Leuk Lymphoma. 2012;53:1124-9.
Dodero A, Spina F, Narni F, et al. Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: Long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect. Leukemia. 2012;26:520-6.
Delioukina M, Zain J, Palmer JM, et al. Reduced-intensity allogeneic hematopoietic cell transplantation using fludarabine-melphalan conditioning for treatment of mature T-cell lymphomas. Bone Marrow Transplant. 2012;47:65-72.
Czajczynska A, Gunther A, Repp R, et al. Allogeneic stem cell transplantation with BEAM and alemtuzumab conditioning immediately after remission induction has curative potential in advanced T-cell non-Hodgkin's lymphoma. Biol Blood Marrow Transplant. 2013;19:1632-7.
Schmitz N, Lenz G, Stelljes M. Allogeneic hematopoietic stem cell transplantation (HSCT) for T-cell lymphomas. Blood. 2018;26:2018-01.
Zhang JY, Briski R, Devata S, et al. Survival following salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL). Am J Hematol. 2018;93:394-400.
Damaj G, Malard F, Hulin C, et al. Efficacy of bendamustine in relapsed/refractory myeloma patients: Results from the French compassionate use program. Leuk Lymphoma. 2012;53:632-4.
O'Connor OA, Falchi L, Lue JK, et al. Oral 5-azacytidine and romidepsin exhibit marked activity in patients with ptcl: A multicenter phase i study. Blood. 2019.
O'Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: Results from the pivotal PROPEL study. J Clin Oncol. 2011;29:1182-9.
Zinzani PL, Venturini F, Stefoni V, et al. Gemcitabine as single agent in pretreated T-cell lymphoma patients: Evaluation of the long-term outcome. Ann Oncol. 2010;21:860-3.
Epperla N, Ahn KW, Litovich C, et al. Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: A CIBMTR analysis. J Hematol Oncol. 2019;12:6.
Kanate AS, DiGilio A, Ahn KW, et al. Allogeneic haematopoietic cell transplantation for extranodal natural killer/T-cell lymphoma, nasal type: A CIBMTR analysis. Br J Haematol. 2018;182:916-20.
Pro B, Advani R, Brice P, et al. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma [published correction appears in Blood. 2018 Jul 26;132(4):458-459]. Blood. 2017;130(25):2709-17.
Ghosh N, Karmali R, Rocha V, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A Center for International Blood and Marrow Transplant Research analysis. J Clin Oncol. 2016;34:3141-9.
Zoellner AK, Fritsch S, Prevalsek D, et al. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma. Bone Marrow Transplant. 2015;50:679-84.
Mediwake H, Morris K, Curley C, et al. Use of brentuximab vedotin as salvage therapy pre-allogeneic stem cell transplantation in relapsed/refractory CD30 positive lympho-proliferative disorders: A single centre experience. Intern Med J. 2017;47:574-8.
Koh KN, Im HJ, Suh JK, et al. Successful use of brentuximab vedotin for refractory anaplastic large cell lymphoma as a bridging therapy to haploidentical stem cell transplantation and maintenance therapy post-transplantation. Pediatr Blood Cancer. 2015;62:1063-5.