1. Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma.
- Author
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Kröger N, Schwerdtfeger R, Kiehl M, Sayer HG, Renges H, Zabelina T, Fehse B, Tögel F, Wittkowsky G, Kuse R, and Zander AR
- Subjects
- Adult, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating toxicity, Female, Graft Survival, Graft vs Host Disease, Graft vs Leukemia Effect, Hematopoietic Stem Cell Transplantation mortality, Hematopoietic Stem Cell Transplantation standards, Humans, Male, Melphalan administration & dosage, Melphalan toxicity, Middle Aged, Multiple Myeloma complications, Multiple Myeloma mortality, Remission Induction methods, Survival Rate, Transplantation Chimera, Transplantation, Autologous immunology, Transplantation, Autologous mortality, Transplantation, Autologous standards, Transplantation, Homologous immunology, Transplantation, Homologous mortality, Transplantation, Homologous standards, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy
- Abstract
We evaluated toxicity, engraftment, chimerism, graft-versus-host disease (GVHD), and response to a dose-reduced allograft after cytoreductive autografting in 17 patients with advanced stage II/III multiple myeloma (MM). After autografting with melphalan (200 mg/m2) the patients received after a median interval of 119 days (range 60-210) a dose-reduced regimen consisting of fludarabine (180 mg/m2), melphalan (100 mg/m2), and antithymocyte globulin (3 x 10 mg/kg) followed by allografting from related (n = 7), mismatched related (n = 2), or unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After dose-reduced allografting all patients became neutropenic (< 0.2 x 10(9)/L) for at least 8 days. All patients engrafted with a median time for leukocyte (> 1 x 10(9)/L) and platelet (> 20 x 10(9)/L) counts of 16 (range, 11-24) and 23 days (range, 12-43), respectively. Complete donor chimerism was detected after a median of 30 days (range, 19-38). Acute GVHD stage II occurred in 4 patients (25%) and grade III GVHD in 2 patients (13%). Chronic GVHD developed in 40% of the patients, but only 1 patient experienced extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of alveolar hemorrhage and pneumonia, resulting in a day 100 mortality rate of 11%. The rate of complete remission with negative immunofixation increased from 18% after autografting to 73% after allografting. After a median follow-up of 17 months after autologous and 13 months after allogeneic transplantation 13 patients are alive and 12 of them free of relapse or progression. The tandem auto-allotransplant protocol is highly active and provides rapid engraftment with complete donor chimerism and tolerable toxicity.
- Published
- 2002
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