The prognosis of patients with myelodysplastic syndromes (MDS) following failure of hypomethylating agent (HMA) therapy is poor. Allogeneic hematopoietic cell transplantation (HCT) can be effective in curing patients who have failed therapy with HMA. However, published results have not addressed the outcomes with HCT in this setting. We identified 125 MDS patients who had been treated with HMA and underwent subsequent HCT. Among these, 68 were considered HMA failures, and 57 responders. Failure was defined as progression to higher grade MDS or acute myeloid leukemia (AML), lack of hematological improvement after at least 4 HMA cycles, or loss of response after initial improvement. Response was defined as showing at least hematological improvement. Outcomes were compared using Cox regression. Overall, 73 of 125 HMA-treated patients (58%) had died by the time of last contact. Median follow-up of survivors, measured from HCT, was 41.9 (range, 2.7-98.5) months. The estimated probability of relapse at 3 years was 56.6% and 34.2% among failing and responding patients, respectively (hazard ratio [HR] 2.1, 95% CI, 1.2-3.66, p< 0.01). The estimated probability of relapse-free survival (RFS) at 3 years was 23.8% and 42% in failing and responding patients, respectively (HR for relapse/death 1.88, 95% CI, 1.19-2.95, p< 0.01). The risk of non-relapse mortality was similar for both groups (HR 1.12, 95% CI, 0.52-2.39, p= 0.77). Failure of treatment with HMA was associated with higher risk of post-HCT relapse than observed in patients responding to HMA. Prospective trials are needed to evaluate the efficacy of novel conditioning regimens and post-HCT maintenance strategies in patients who have failed HMA pre-HCT.
- myelodysplastic syndromes (MDS)