title: Low-dose total body irradiation and fludarabine conditioning for HLA class I-mismatched donor stem cell transplantation and immunologic recovery in patients with hematologic malignancies: a multicenter trial.
abstract: HLA-mismatched grafts are a viable alternative source for patients without HLA-matched donors receiving ablative hematopoietic cell transplantation (HCT), although their use in reduced intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT has been not well established. Here, we extended HCT to recipients of HLA class I-mismatched grafts to investigate whether NMA conditioning can establish stable donor engraftment. Fifty-nine patients were conditioned with fludarabine (Flu) 90 mg/m(2) and 2 Gy total body irradiation (TBI), followed by immunosuppression with cyclosporine (CsA) 5.0 mg/kg twice a day and mycophenolate mofetil (MMF) 15 mg/kg 3 times a day for transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from related (n = 5) or unrelated donors (n = 54) with 1 antigen +/- 1 allele HLA class I mismatch or 2 HLA class I allele mismatches. Sustained donor engraftment was observed in 95% of the evaluable patients. The incidence of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) was 69% and 41%, respectively. The cumulative probability of nonrelapse mortality (NRM) was 47% at 2 years. Two-year overall and progression-free survival (OS, PFS) was 29% and 28%, respectively. NMA conditioning with Flu and low-dose TBI, followed by HCT using HLA class I-mismatched donors leads to successful engraftment and long-term survival; however, the high incidence of aGVHD and NRM needs to be addressed by alternate GVHD prophylaxis regimens.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109-1024, USA.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Finn B
authors.initials: FB
authors.lastname: Petersen
authors.forename: James C
authors.initials: JC
authors.lastname: Wade
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001772:Blood Cell Count; D002452:Cell Count; D003141:Communicable Diseases / Q000209:etiology; D003713:Dendritic Cells / Q000166:cytology; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000175:diagnosis; D019337:Hematologic Neoplasms / Q000628:therapy*; D006648:Histocompatibility / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D011183:Postoperative Complications; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014916:Whole-Body Irradiation / Q000379:methods*; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine