title: Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS.
abstract: Although allogeneic hematopoietic cell transplantation (HCT) has proven curative potential for myelodysplastic syndrome, relapse after HCT remains a problem. Pretransplantation cytoreduction with induction chemotherapy (IC) has been used to reduce relapse rates but is associated with significant toxicity and mortality. Hypomethylating agents may achieve cytoreduction with limited toxicity; however, data on the effect of pre-HCT hypomethylation on post-HCT outcomes are limited. We retrospectively reviewed results in 68 patients who underwent allogeneic HCT for myelodysplastic syndrome or acute myeloid leukemia transformed from MDS. Thirty-five patients had received cytoreduction with azacitidine before HCT with either a high-dose (40%) or a reduced-intensity (60%) conditioning regimen, and 33 had undergone IC before HCT with high-dose conditioning. The estimated 1-year overall survival (OS) was 57% in the azacitidine group and 36% in the IC group. The risk of post-HCT mortality (hazard ratio, 0.68; 95% confidence interval, 0.35-1.30), nonrelapse mortality (hazard ratio, 0.99; 95% confidence interval, 0.41-2.34), and relapse (hazard ratio, 0.34; 95% confidence interval, 0.41-2.34) were lower in the azacitidine group compared to the IC group, but only the hazard for relapse was significantly lower. After adjustment for cytogenetic risk, International Prognostic Scoring System, and donor, the rates of post-HCT relapse for the 2 cohorts were similar. Although the current study was retrospective and nonrandomized and needs to be interpreted in this context, the results add to the growing evidence that pre-HCT therapy with azacitidine is associated with less toxicity than IC and may allow for similar post-HCT outcomes.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA, USA.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Gerds
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000601:surgery*; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine