HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.
We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/microL) and platelet recovery (>20,000/microL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.
Luznik
Leo
L
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
O'Donnell
Paul V
PV
Symons
Heather J
HJ
Chen
Allen R
AR
Leffell
M Susan
MS
Zahurak
Marianna
M
Gooley
Ted A
TA
Piantadosi
Steve
S
Kaup
Michele
M
Ambinder
Richard F
RF
Huff
Carol Ann
CA
Matsui
William
W
Bolaños-Meade
Javier
J
Borrello
Ivan
I
Powell
Jonathan D
JD
Harrington
Elizabeth
E
Warnock
Sandy
S
Flowers
Mary
M
Brodsky
Robert A
RA
Sandmaier
Brenda M
BM
Storb
Rainer F
RF
Jones
Richard J
RJ
Fuchs
Ephraim J
EJ
D000328:Adult; D000368:Aged; D016913:Blood Component Transfusion; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000601:surgery*; D006457:Hemoglobinuria, Paroxysmal / Q000601:surgery*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011182:Postoperative Care / Q000379:methods; D011183:Postoperative Complications / Q000453:epidemiology; D011994:Recombinant Proteins; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine; D000069585:Filgrastim; D016559:Tacrolimus