title: Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.
abstract: Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred in 50% of patients. Of the 63 URD HSCT patients, 54% were alive, 37% in CR, 3% PR, and 14% with disease progression or relapse. Related and unrelated nonmyeloablative HSCT is feasible and potentially curative in patients with advanced hematological malignancies who have no other treatment options.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.forename: Michael
authors.initials: M
authors.lastname: Maris
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: David G
authors.initials: DG
authors.lastname: Malone
authors.forename: Lyle
authors.initials: L
authors.lastname: Feinstein
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederweiser
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Edward
authors.initials: E
authors.lastname: Agura
authors.forename: Marie-Trse
authors.initials: MT
authors.lastname: Little
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Sahebi
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014181:Transplantation Immunology; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
chemical_list: D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine