title: Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome after conditioning with busulfan and fractionated total body irradiation is associated with low relapse rate but considerable nonrelapse mortality.
abstract: The objectives of this study were to develop transplantation regimens for patients with advanced myelodysplastic syndrome (MDS) that would be associated with low transplantation-related mortality and improved relapse-free survival. Sixty patients with advanced MDS or acute myeloid leukemia evolving from MDS (sAML), 12 to 62 years old (median, 40 years), were conditioned with busulfan (7 mg/kg) and TBI (6 x 200 cGy) (BU/TBI) and received transplants from related (n = 20) or unrelated donors (n = 40). By French-American-British (FAB) criteria, 21 patients had refractory anemia with excess blasts (RAEB), 16 had RAEB in transformation (RAEB-T), 15 had sAML, and 8 had chronic myelomonocytic leukemia (CMML). By International Prognostic Scoring System (IPSS) criteria, 1 patient had low, 10 had intermediate-1, 13 had intermediate-2, and 31 had high-risk MDS (5 patients had proliferative CMML). All evaluable patients achieved sustained engraftment. The cumulative incidence (CI) of acute GVHD grades II to IV was 83% with unrelated donors and 85% with related donors. The CI of relapse was 25% at 3 years. The incidence of nonrelapse mortality (NRM) at 100 days was 38%. The Kaplan-Meier estimate of survival was 26% at 3 years. Major causes of death were relapse, organ failure, GVHD, and infection. In multivariate analysis, improved relapse-free survival was associated with good cytogenetic risk (P = .002) and shorter disease duration (P = .004). NRM was increased with longer disease duration (P = .0002), positive cytomegalovirus serology (P = .02), and male sex (P = .02). Relapse was associated with poor cytogenetic risk (P = .0004). Thus, BU/TBI conditioning as used in this trial was associated with relapse rates comparable to those observed with a previously used more intensive regimen combining BU/TBI with cyclophosphamide. However, despite the omission of cyclophosphamide, transplantation-related morbidity and mortality were considerable, particularly with transplants from unrelated donors. Future trials should explore the efficacy and tolerability of reduced-intensity conditioning regimens.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jurado
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Anderson
authors.forename: Eileen
authors.initials: E
authors.lastname: Bryant
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Kris
authors.initials: K
authors.lastname: Doney
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: John
authors.initials: J
authors.lastname: Hansen
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Jerry
authors.initials: J
authors.lastname: Radich
authors.forename: George
authors.initials: G
authors.lastname: Sale
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: James
authors.initials: J
authors.lastname: Wade
authors.forename: Robert
authors.initials: R
authors.lastname: Witherspoon
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage*; D002423:Cause of Death; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014916:Whole-Body Irradiation
chemical_list: D002066:Busulfan