Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma

• Published in: Blood 2002-08, Vol.100 (3), p.755-760
• Main Authors: Kröger, Nicolaus, Schwerdtfeger, Rainer, Kiehl, Michael, Sayer, Herbert Gottfried, Renges, Helmut, Zabelina, Tatjana, Fehse, Boris, Tögel, Florian, Wittkowsky, Georg, Kuse, Rolf, Zander, Axel Rolf
• Format: Article
• Language: English
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - toxicity; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Female; Graft Survival; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Hematopoietic Stem Cell Transplantation - standards; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - toxicity; Middle Aged; Multiple Myeloma - complications; Multiple Myeloma - mortality; Multiple Myeloma - therapy; Remission Induction - methods; Survival Rate; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Chimera; Transplantation, Autologous - immunology; Transplantation, Autologous - mortality; Transplantation, Autologous - standards; Transplantation, Homologous - immunology; Transplantation, Homologous - mortality; Transplantation, Homologous - standards; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-01-0131

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 × 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 × 109/L) for at least 8 days. All patients engrafted with a median time for leukocyte (> 1 × 109/L) and platelet (> 20 × 109/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.