High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease.
Because of its potent immunosuppressive yet stem cell-sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)-matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell-replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).
Luznik
Leo
L
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. luznile@jhmi.edu
Bolaños-Meade
Javier
J
Zahurak
Marianna
M
Chen
Allen R
AR
Smith
B Douglas
BD
Brodsky
Robert
R
Huff
Carol Ann
CA
Borrello
Ivan
I
Matsui
William
W
Powell
Jonathan D
JD
Kasamon
Yvette
Y
Goodman
Steven N
SN
Hess
Allan
A
Levitsky
Hyam I
HI
Ambinder
Richard F
RF
Jones
Richard J
RJ
Fuchs
Ephraim J
EJ
D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide