title: HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen.
abstract: Allogeneic blood or marrow transplantation (BMT) is a curative therapy for chronic myeloid leukemia (CML). We have previously reported that the pharmacologic targeting of busulfan combined with cyclophosphamide (TBU/CY) can minimize regimen-related toxicity while preserving antileukemic effects. We report here on 131 consecutive chronic-phase CML patients treated with allogeneic related BMT using a TBU/CY preparative regimen, where the busulfan dose was targeted to achieve a steady-state plasma concentration of at least 900 ng/mL. The median age of the patients was 43 years (range, 14-66 years). Estimates of the probabilities of nonrelapse mortality, relapse, survival, and disease-free survival 3 years after transplantation were 14%, 8%, 86%, and 78%, respectively. Age had no statistically significant effect on survival. Although approximately 60% of the patients developed clinically extensive chronic graft-versus-host disease, the median Karnofsky score at last contact date among survivors was 95%. Of surviving patients, 11% were molecularly positive for the bcr-abl mRNA at last contact, with a median level of bcr-abl transcripts of 4.6 copies/microg RNA. These data suggest that TBU/CY is a very effective preparative regimen for CML in chronic phase, associated with an expected survival at 3 years of approximately 85%, with most patients being in molecular remission.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, D4-100, 1100 Fairview Ave N, Seattle, WA 98109, USA. jradich@fhcrc.org
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Ted
authors.initials: T
authors.lastname: Gooley
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Reginald
authors.initials: R
authors.lastname: Clift
authors.forename: Mary
authors.initials: M
authors.lastname: Flowers
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: John
authors.initials: J
authors.lastname: Slattery
authors.forename: Debbie
authors.initials: D
authors.lastname: Sultan
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan