Summary:
We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5–11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan–Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.
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References
De Vita Jr VT, Hubbard SM . Hodgkin's disease. N Engl J Med 1993; 328: 560–565.
Linch DC, Winfield D, Goldstone AH et al. Dose intensification with autologous bone marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet 1993; 341: 1051–1054.
Anderson JE, Litzow MR, Appelbaum FR et al. Allogeneic, syngeneic and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience. J Clin Oncol 1993; 11: 2342–2350.
Philip GL, Wolff SN, Herzig RH et al. Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation. Blood 1989; 73: 2086–2092.
Nademanee A, O'Donnel MR, Snyder DS et al. High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodkin's disease: results in 85 patients with analysis of prognostic factors. Blood 1995; 85: 1381–1390.
Horning SJ, Chao NJ, Negrin RS et al. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood 1997; 89: 801–813.
Gianni AM, Siena S, Bregni M et al. High-dose sequential chemo-radiotherapy with peripheral blood progenitor cell support for relapsed or refractory Hodgkin's disease. A 6-year update. Ann Oncol 1993; 4: 889–891.
Yahalom J, Gulati SC, Toia M et al. Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease. J Clin Oncol 1993; 6: 1062–1070.
Carella AM, Congiu AM, Gaozza E et al. High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: an Italian Study Group report. J Clin Oncol 1988; 6: 1411–1416.
Reece DE, Barnett MJ, Connors ME et al. Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 1991; 9: 1871–1879.
Lazarus HM, Crilley P, Ciobanu N et al. High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma. J Clin Oncol 1992; 10: 1682–1689.
Bierman PJ, Bagin RG, Jagannath S et al. High-dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease; long-term follow-up in 128 patients. Ann Oncol 1993; 4: 767–773.
Burns LJ, Daniels KA, McGlave PB et al. Autologous stem cell transplantation for refractory and relapsed Hodgkin's disease; factors predictive of prolonged survival. Bone Marrow Transplant 1995; 16: 13–18.
Wheeler C, Eickhoff C, Elias A et al. High-dose cyclophosphamide, carmustine and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant 1997; 3: 98–106.
Spinolo JA, Jagannath S, Velazquez et al. Cisplatin-CBV with autologous bone marrow transplantation for relapsed Hodgkin's disease. Leukemia Lymphoma 1993; 9: 71–77.
Weaver CH, Appelbaum FR, Petersen FB et al. High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy. J Clin Oncol 1993; 11: 1329–1335.
Reece DE, Connors ME, Spinelli JJ et al. Intensive therapy with cyclophosphamide, carmustine, etoposide±cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood 1994; 83: 1193–1199.
Chopra R, Mc Millan AK, Linch DC et al. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor risk Hodgkin's disease. A single-center eight-year study of 155 patients. Blood 1993; 81: 1137–1145.
Lumley MA, Milligan DW, Knechtli CJC et al. High lactate dehydrogenase level is associated with an adverse outlook in autografting for Hodgkin's disease. Bone Marrow Transplant 1996; 17: 383–388.
Rapaport AP, Rowe JM, Kouides PA et al. One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome. J Clin Oncol 1993; 11: 2351–2361.
Crump M, Smith AM, Brandwein J et al. High-dose etoposide and melphalan and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant. J Clin Oncol 1993; 11: 704–711.
Weaver CH, Petersen FB, Appelbaum FR et al. High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma. J Clin Oncol 1994; 12: 2559–2566.
Schiffman K, Buckner CD, Maziarz R et al. High-dose busulfan, melphalan, and thiotepa followed by autologous peripheral blood stem cell transplantation in patients with aggressive lymphoma or relapsed Hodgkin's disease. Biol Blood Marrow Transplant 1997; 3: 261–266.
Brunvand MW, Bensinger WI, Soll E et al. High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells. Bone Marrow Transplant 1996; 18: 131–141.
Gutierrez-Delgado F, Maloney D, Press OW et al. Autologous stem cell transplantation for non-Hodgkin lymphoma: comparison of radiation-based and chemotherapy-only preparative regimens. Bone Marrow Transplant 2001; 28: 455–461.
Carbone PP, Kaplan HS, Musshoff K et al. Report of the Committee on Hodgkin's disease Staging. Cancer Res 1971; 31: 1860–1861.
Lukes RJ, Butler JJ . The pathology and nomenclature of Hodgkin's disease. Cancer Res 1966; 26: 1063–1081.
Thomas ED, Storb R . Technique for human marrow grafting. Blood 1970; 36: 507–515.
Bensinger W, Singer J, Appelbaum F et al. Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte colony stimulating factor. Blood 1993; 81: 3158–3163.
Rowley SD, Bensinger W, Gooley T et al. The effect of cell concentration on bone marrow and peripheral blood stem cell cryopreservation. Blood 1994; 83: 2731–2736.
Bast R, Ritz J, Lipton J et al. Elimination of leukemic cells from human bone marrow using monoclonal antibody and complement. Cancer Res 1983; 43: 1389–1394.
Hill R, Mazza P, Amos D et al. Engraftment in 86 patients with lymphoid malignancy after autologous marrow transplantation. Bone Marrow Transplant 1989; 4: 69–74.
Bensinger W, Appelbaum F, Rowley S et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 1995; 13: 2547–2555.
Fefer A, Benyunes M, Higuchi C et al. Interleukin-2±lymphocytes as consolidative immunotherapy after autologous bone marrow transplantation for hematologic malignancies. Acta Haematol 1993; 89: 2–7.
Bearman S, Appelbaum F, Buckner C et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.
Crawford SW . Critical care and respiratory failure. In: Thomas ED, Forman SJ, Blume KG (eds). Stem Cell Transplantation. Blackwell Scientific: Boston, MA, 1999, pp 712–722.
Strasser SI, McDonald GB . Gastrointestinal and hepatic complications. In: Thomas ED, Forman SJ, Blume KG (eds). Stem Cell Transplantation. Blackwell Scientific: Boston, MA, 1999, pp 627–658.
Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 30: 695–706.
Poen JC, Hoppe RT, Horning SJ . High-dose therapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease: the impact of involved field radiotherapy on patterns of failure and survival. Int J Radiat Oncol Biol Phys 1996; 36: 3–12.
Martin A, Fernandez-Jimenez MC, Caballero M et al. Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease. Br J Haematol 2001; 113: 161–171.
Sureda A, Arranz A, Iriondo A et al. Autologous stem cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol 2001; 19: 1395–1404.
Wheeler C, Antin JH, Churchill WH et al. Cyclophosphamide, carmustine and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. J Clin Oncol 1990; 8: 648–656.
Andre M, Henry-Amar M, Blaise D et al. Comparison of high-dose chemotherapy and autologous stem cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case control study. Societe Francaise de Greffe de Moelle. J Clin Oncol 1999; 17: 222–229.
Jagannath S, Armitage JO, Dicke KA et al. Prognostic factors for response and survival after high-dose cyclophosphamide, carmustine, and etoposide. J Clin Oncol 1989; 7: 179–185.
Brice P, Bouabdallah R, Moreau P et al. Prognostic factors for survival after high-dose therapy and autologous stem cell transplantation for patients with relapsing Hodgkin's disease: analysis of 280 patients from the French registry. Societe Francaise de Gfreffe de Moelle. Bone Marrow Transplant 1997; 20: 21–26.
Yuen A, Rosenberg S, Hope R et al. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease. Blood 1997; 89: 814–822.
Arranz R, Tomas JF, Gil-Fernandez JJ et al. Autologous stem cell transplantation for poor prognostic Hodgkin's disease: comparative results with two CBV regimens and importance of disease status at transplant. Bone Marrow Transplant 1998; 21: 779–786.
Moreau P, Fleury J, Brice P et al. Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin's disease: retrospective analysis of 158 cases from the French registry. Bone Marrow Transplant 1998; 21: 787–793.
Hasenclever D, Diehl V . A prognostic score for advanced Hodgkin's disease. N Engl J Med 1998; 339: 1506–1514.
Moskowitz CH, Nimer SD, Zelenetz ED et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood 2001; 97: 616–623.
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Supported by grants from the National Institutes of Health CA 18029, CA 47748, CA 15704 and the Jose Carreras Foundation against Leukemia. FG-D was supported by a grant from Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
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Gutierrez-Delgado, F., Holmberg, L., Hooper, H. et al. Autologous stem cell transplantation for Hodgkin's disease: busulfan, melphalan and thiotepa compared to a radiation-based regimen. Bone Marrow Transplant 32, 279–285 (2003). https://doi.org/10.1038/sj.bmt.1704110
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DOI: https://doi.org/10.1038/sj.bmt.1704110
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