title: Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation.
abstract: Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P =.006), patients in first CR (28% versus 3%, P =.008), and HLA-matched sibling donors (81% versus 40%, P =.001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P =.036), and lower cumulative incidence of relapse-related mortality (P =.029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. mdelima@mdanderson.org
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Athanasios
authors.initials: A
authors.lastname: Anagnostopoulos
authors.forename: Mark
authors.initials: M
authors.lastname: Munsell
authors.forename: Munir
authors.initials: M
authors.lastname: Shahjahan
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
authors.forename: Cindy
authors.initials: C
authors.lastname: Ippoliti
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Michele
authors.initials: M
authors.lastname: Donato
authors.forename: Joyce
authors.initials: J
authors.lastname: Neumann
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
mesh_terms: D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D018579:Patient Selection; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents