title: HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.
abstract: 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.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Symons
authors.forename: Allen R
authors.initials: AR
authors.lastname: Chen
authors.forename: M Susan
authors.initials: MS
authors.lastname: Leffell
authors.forename: Marianna
authors.initials: M
authors.lastname: Zahurak
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Steve
authors.initials: S
authors.lastname: Piantadosi
authors.forename: Michele
authors.initials: M
authors.lastname: Kaup
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Huff
authors.forename: William
authors.initials: W
authors.lastname: Matsui
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Powell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Harrington
authors.forename: Sandy
authors.initials: S
authors.lastname: Warnock
authors.forename: Mary
authors.initials: M
authors.lastname: Flowers
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Rainer F
authors.initials: RF
authors.lastname: Storb
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine; D000069585:Filgrastim; D016559:Tacrolimus