Factors Determining Responses to Azacitidine in Patients with Myelodysplastic Syndromes and Acute Myeloid Leukemia with Early Post-Transplantation Relapse: A Prospective Trial

•Azacitidine given early after transplantation for myelodysplastic syndromes is well tolerated•Azacitidine induces remissions after early post-transplantation relapse in patients with myelodysplastic syndromes•Early detection and intervention with azacitidine may improve outcome•The clonal composition of myelodysplastic syndromes changes with relapse and during therapy

Retrospective analyses suggest a benefit of therapy with hypomethylating agents in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective trial in 39 patients with MDS or AML who relapsed within 100 days of HCT. Relapse was documented by morphology, flow cytometry, or cytogenetics. Treatment consisted of 5-azacitidine, 75 mg/m2/day for 7 days, administered every 28 days. Patients were followed by sequential marrow examinations, and responses were assessed at 6 months. There were 3 complete remissions and 9 partial remissions (30%); an additional 3 patients had stable disease by International Working Group criteria. In multivariate analysis, only the type of induction chemotherapy given before HCT was significantly associated with post-HCT response to 5-azacitidine and overall survival (P = .004). These data support the use of hypomethylating therapy for post-HCT relapse in patients with MDS and AML and suggest that pre-HCT therapy may affect the likelihood of response to this salvage approach.