Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS

Biol Blood Marrow Transplant. 2012 Aug;18(8):1211-8. doi: 10.1016/j.bbmt.2012.01.009. Epub 2012 Jan 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / adverse effects
  • Azacitidine / therapeutic use*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / surgery*
  • Recurrence
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning / methods
  • Treatment Outcome
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Azacitidine