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.
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.
de Lima
Marcos
M
Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. mdelima@mdanderson.org
Anagnostopoulos
Athanasios
A
Munsell
Mark
M
Shahjahan
Munir
M
Ueno
Naoto
N
Ippoliti
Cindy
C
Andersson
Borje S
BS
Gajewski
James
J
Couriel
Daniel
D
Cortes
Jorge
J
Donato
Michele
M
Neumann
Joyce
J
Champlin
Richard
R
Giralt
Sergio
S
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
D007166:Immunosuppressive Agents