Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma.
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.
Bone Marrow Transplantation, University Hospital Hamburg, Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Nicolaus
N
Kröger
Rainer
R
Schwerdtfeger
Michael
M
Kiehl
Herbert Gottfried
HG
Sayer
Helmut
H
Renges
Tatjana
T
Zabelina
Boris
B
Fehse
Florian
F
Tögel
Georg
G
Wittkowsky
Rolf
R
Kuse
Axel Rolf
AR
Zander
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality / Q000592:standards; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction / Q000379:methods; D015996:Survival Rate; D018183:Transplantation Chimera; D014182:Transplantation, Autologous / Q000276:immunology / Q000401:mortality / Q000592:standards; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality / Q000592:standards; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan