title: HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies.
abstract: A hematopoietic cell transplantation (HCT) approach was developed for elderly or ill patients with hematologic malignancies that employed nonmyeloablative conditioning to avoid common regimen-related toxicities and relied on graft-versus-tumor effects for control of malignancy. Eighty-nine patients, median age 53 years, were given fludarabine (90 mg/m2) and 2 Gy total body irradiation. Marrow (n = 18) or granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral blood mononuclear cells (G-PBMCs; n = 71) were transplanted from unrelated donors matched for human leukocyte antigen A (HLA-A), -B, -C antigens and -DRB1 and -DQB1 alleles. Postgrafting immunosuppression included mycophenolate mofetil and cyclosporine. Donor T-cell chimerism was higher for G-PBMCs compared with marrow recipients. Durable engraftment was observed in 85% of G-PBMCs and 56% of marrow recipients. Cumulative probabilities of grade II, III, and IV acute graft-versus-host disease (GVHD) were 42%, 8%, and 2%, respectively. Nonrelapse mortality at day 100 and at 1 year was 11% and 16%, respectively. One-year overall survivals and progression-free survivals were 52% and 38%, respectively. G-PBMC recipients had improved survival (57% vs 33%) and progression-free survival (44% vs 17%) compared with marrow recipients. HLA-matched unrelated donor HCT after nonmyeloablative conditioning is feasible in patients ineligible for conventional HCT. G-PBMCs conferred higher donor T-cell chimerism, greater durable engraftment, and better progression-free and overall survivals compared with marrow.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024. mmaris@fhcrc.org
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Monic
authors.initials: M
authors.lastname: Stuart
authors.forename: David
authors.initials: D
authors.lastname: Maloney
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Peter
authors.initials: P
authors.lastname: McSweeney
authors.forename: Michael
authors.initials: M
authors.lastname: Pulsipher
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Ed
authors.initials: E
authors.lastname: Agura
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.forename: John
authors.initials: J
authors.lastname: Slattery
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Karl
authors.initials: K
authors.lastname: Blume
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015994:Incidence; D007938:Leukemia / Q000401:mortality* / Q000628:therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000628:therapy; D015479:Leukemia, Myelomonocytic, Acute / Q000401:mortality / Q000628:therapy; D017710:Lymphocyte Transfusion; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy; D009173:Mycophenolic Acid / Q000493:pharmacokinetics; D009196:Myeloproliferative Disorders / Q000401:mortality / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D014019:Tissue Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
chemical_list: D000903:Antibiotics, Antineoplastic; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine