Abstract
Outcome is poor with conventional therapy for relapsed transformed non-Hodgkin's lymphoma (NHL). Autologous SCT has been successfully employed; however the impact of allogeneic SCT has not been well defined. We therefore studied 40 consecutive patients who received allogeneic SCT for relapsed composite and transformed NHL (25 transformed, 8 composite (same site) and 7 discordant (different sites)) with related (n=25) and unrelated donors (n=15) to evaluate long-term outcome. Conditioning was myeloablative in the majority (39 of 40). Of 40 patients, 11 survive with median follow-up of 25 months. Death occurred in similar proportions due to relapsed NHL (n=14) or treatment-related complications (transplant-related mortality, TRM; n=15). The cumulative incidence of TRM was 36% at 3 years and disease relapse was 42% at 5 years. Probability of 2- and 5-year event-free survival is 36 and 23% with overall survival 39 and 23%. Performance of SCT within 1 year of NHL diagnosis predicted improved outcome. Relapse and TRM remain significant problems in this setting, indicating the need for strategies whereby patients at high risk of transformation should be selected for early SCT, ideally before their actual transformation.
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References
Yuen A, Kamel OW, Halpern J, Horning SJ . Long-term survival after histologic transformation of low-grade follicular lymphoma. J Clin Oncol 1995; 13: 1726–1733.
Gine E, Montoto S, Bosch F, Arenillas L, Mercadal S, Villamor N et al. The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma. Ann Oncol 2006; 17: 1539–1545.
Bastion Y, Sebban C, Berger F, Felman P, Salles G, Dumontet C et al. Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol 1997; 15: 1587–1594.
Hubbard S, Chabner BA, DeVita Jr VT, Simon R, Berard CW, Jones RB et al. Histologic progression in non-Hodgkin's lymphoma. Blood 1982; 59: 258–264.
Al-Tourah A, Chhanabahi M, Gill K . Incidence, predictive factors and outcome of transformed lymphoma: a population-based study from British Columbia. Ann Oncol 2005; 16 (Abstract): 64 (abstract).
Montoto SDA, Matthews J, Calaminici M, Norton AJ, Amess J, Vinnicombe S et al. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol 2007; 25: 2426–2433.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med 2002; 346: 235–242.
Kaminski M, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L et al. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol 2001; 19: 3918–3928.
Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC et al. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol 2004; 15: 511–516.
Foran J, Apostolidis J, Papamichael D, Norton AJ, Matthews J, Amess JA et al. High-dose therapy with autologous haematopoietic support in patients with transformed follicular lymphoma: a study of 27 patients from a single centre. Ann Oncol 1998; 9: 865–869.
Friedberg J, Neuberg D, Gribben JG, Mauch P, Anderson KC, Soiffer RJ et al. Autologous bone marrow transplantation after histologic transformation of indolent B cell malignancies. Biol Blood Marrow Transplant 1999; 5: 262–268.
Williams C, Harrison CN, Lister TA, Norton AJ, Blystad AK, Coiffier B et al. High-dose therapy and autologous stem-cell support for chemosensitive transformed low-grade follicular non-Hodgkin's lymphoma: a case-matched study from the European Bone Marrow Transplant Registry. J Clin Oncol 2001; 19: 727–735.
Chen C, Crump M, Tsang R, Stewart AK, Keating A . Autotransplants for histologically transformed follicular non-Hodgkin's lymphoma. Br J Haematol 2001; 113: 202–208.
Dhedin N, Giraudier S, Gaulard P, Esperou H, Ifrah N, Michallet M et al. Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database. Br J Haematol 1999; 107 (Societ Francaise de Greffe de Moelle): 154–161.
Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J et al. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol 1999; 10: 527–532.
Doocey R, Toze CL, Connors JM, Nevill TJ, Gascoyne RD, Barnett MJ et al. Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma. Br J Haematol 2005; 131: 223–230.
Rezvani A, Storer B, Maris M, Sorror ML, Agura E, Maziarz RT et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma. JCO 2008; 26: 211–217.
Ratanatharathorn V, Uberti J, Karanes C, Abella E, Lum LG, Momin F et al. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma. Blood 1994; 84: 1050–1055.
Peniket A, Ruiz de Elvira MC, Taghipour G, Cordonnier C, Gluckman E, de Witte T et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplantation 2003; 31: 667–678.
van Besien K, de Lima M, Giralt SA, Moore Jr DF, Khouri IF, Rondon G et al. Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. Bone Marrow Transplant 1997; 19: 977–982.
van Besien K, Loberiza Jr FR, Bajorunaite R, Armitage JO, Bashey A, Burns LJ et al. Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 2003; 102: 3521–3529.
Toze C, Shepherd JD, Connors JM, Voss NJ, Gascoyne RD, Hogge DE et al. Allogeneic bone marrow transplantation for low-grade lymphoma and chronic lymphocytic leukemia. Bone Marrow Transplantation 2000; 25: 605–612.
Verdonck L, Dekker AW, Lokhorst HM, Petersen EJ, Nieuwenhuis HK . Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin's lymphoma. Blood 1997; 90: 4201–4205.
Jaffe E, Harris NL, Stein H, Vardiman JW . World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon, France, 2001.
Carbone P, Kaplan HS, Musshoff K, Smithers DW, Tubiana M . Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 1971; 31: 1860–1861.
Shipp MA . The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993; 329: 987–994.
Canellos G, DeVita VT, Young RC, Chabner BA, Schein PS, Johnson RE et al. Therapy of advanced lymphocytic lymphoma a preliminary report of a randomized trial between combination chemotherapy (CVP) and intensive radiotherapy. Br J Cancer 1975; 2: 474–480.
Al-Tourah AJ, Gill KK, Hoskins PJ, Klasa RJ, Savage KJ, Sehn LH et al. The impact of initial treatment of advanced stage indolent lymphoma on the risk of transformation. J Clin Oncol 2006; 24 (abstract, ASCO): 7510.
Armitage J, Corder MP, Leimert JT, Dick FR, Elliot TE . Advanced diffuse histiocytic lymphoma treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) without maintenance therapy. Cancer Treat Rep 1980; 64: 649–654.
Coiffier B, Lepage E, Herbrecht R . Mabthera (rituximab) plus CHOP is superior to CHOP alone in elderly patients with diffuse large B-cell lymphoma (DLCL): interim results of a randomized GELA trial. Blood 2000; 96: 223a (abstract 950).
Cheson B, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17: 1244.
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314: 729–735.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.
Sullivan K, Forman SJ, Blume KG, Thomas ED . Graft-Versus-Host Disease in Bone Marrow Transplantation. Blackwell: Oxford, 1994, pp 339–362.
Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Pepe M, Mori M . Kaplan–Meier, marginal or conditional probability curves in summarizing competing risks failure time data. Stat Med 1993; 12: 737–751.
Cox D . Regression models and life-tables. J R Stat Soc 1972; 34: 187–220.
Toze C, Barnett MJ, Connors JM, Gascoyne RD, Voss NJ, Nantel SH et al. Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation. Br J Haematol 2004; 127: 311–321.
Seropian S, Bahceci E, Cooper DL . Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma. Bone Marrow Transplant 2003; 32: 763–769.
Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G et al. Outcomes after alemtuzumab-containing reduced intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 2004; 104: 3865–3871.
Robinson S, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 2002; 100: 4310–4316.
Khouri I, Saliba R, Giralt S . Long term remission and low mortality achieved with cisplatin, fludarabine, cytarabine nonablative preparative regimen and allogeneic stem cell transplantation (AST) for histologically aggressive non Hodgkins lymphoma (NHL). Blood 2001; 98: 190a (abstract).
Kottaridis P, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S et al. Mackinnon S. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.
Izutsu K, Kanda Y, Ohno H, Sao H, Ogawa H, Miyazaki Y et al. Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program. Blood 2004; 103: 1955–1960.
Acknowledgements
We thank Janet Nitta, Linda Lei and Wendy Zhang for assistance with data management and statistical analysis, the nursing, medical and support staff at the Leukemia/BMT Program, the Lymphoma Group at the BC Cancer Agency and the physicians of British Columbia, Manitoba, Saskatchewan and Yukon for referral of patients.
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Ramadan, K., Connors, J., Al-Tourah, A. et al. Allogeneic SCT for relapsed composite and transformed lymphoma using related and unrelated donors: long-term results. Bone Marrow Transplant 42, 601–608 (2008). https://doi.org/10.1038/bmt.2008.220
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DOI: https://doi.org/10.1038/bmt.2008.220
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