Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma.
We evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated with melphalan/fludarabine followed by allogeneic stem cell transplantation. The cumulative risk at 1 year for treatment-related mortality (TRM) was 18% (95% confidence interval [CI], 12%-28%). In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16-6.74; P =.02), relapse (HR, 4.14; 95% CI, 2.04-8.38; P <.001), event-free survival (HR, 3.11; 95% CI, 1.77-5.46; P <.001), and overall survival (HR, 2.69; 95% CI, 1.35-5.35; P =.005). In addition, relapse was also significantly diminished by chronic graft-versus-host disease (GVHD) in a time-dependent Cox model (HR, 0.37; 95% CI, 0.16-0.87; P =.02). At transplantation, 8% of the patients were in complete remission, whereas 27% had progressive disease. After allografting, 49% achieved complete remission, and 38% achieved partial remission. In a subgroup of patients with chemosensitivity at transplantation and no relapse after prior high-dose chemotherapy who underwent transplantation with peripheral blood stem cells (n = 46), the cumulative risk of TRM at 1 year was only 8% (95% CI, 1%-54%). The 2-year estimated event-free and overall survival was 60% (95% CI, 42%-78%) and 75% (95% CI, 59%-91%), respectively, for related donors (n = 34) and was 81% (95% CI, 59%-100%) and 92% (95% CI, 76%-100%), respectively, for unrelated donors (n = 12).
Kröger
Nicolaus
N
Bone Marrow Transplantation, University Hospital Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Perez-Simon
Jose A
JA
Myint
Han
H
Klingemann
Hans
H
Shimoni
Avichai
A
Nagler
Arnon
A
Martino
Rodrigo
R
Alegre
Adrian
A
Tomas
Jose F
JF
Schwerdtfeger
Rainer
R
Kiehl
Michael
M
Fauser
Axel
A
Sayer
Herbert Gottfried
HG
Leon
Angel
A
Beyer
Jörg
J
Zabelina
Tatjana
T
Ayuk
Francis
F
San Miguel
Jesus F
JF
Brand
Ronald
R
Zander
Axel Rolf
AR
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002908:Chronic Disease; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan