Hypomethylating Agents for Relapse after Allogeneic Hematopoietic Cell Transplantation in Myeloid Malignancies: A Case Series and Review of the Literature

Abstract

Background/aims: Relapse is a leading cause of mortality after allogeneic hematopoietic cell transplantation (HCT). Hypomethylating agents (HMAs) have immunomodulatory properties, including augmenting tumor antigen presentation that may enhance the graft-versus-leukemia effect. Moreover, inhibitory effects on T-cell activation and cytokine production may lead to a lower incidence of graft-versus-host disease (GVHD). Our aim was to describe outcomes in patients treated with HMAs for relapse after HCT.

Methods: Subjects were retrospectively identified as patients with relapse or loss of donor chimerism after HCT for myeloid malignancies treated with HMAs at the University of Pittsburgh.

Results: Thirteen patients were identified, with a median age of 57 years and a median time to relapse of 98 days. Nine of 12 (75%) evaluable patients had a complete remission (CR). Grade I-IV acute GVHD involving the liver occurred in 6 patients. Cases of acute liver GVHD were diagnosed clinically based on the elevation of liver function tests. The median survival was 14.3 months from the time of relapse.

Conclusion: HMAs for relapse after HCT can be effective in inducing a CR. This may be due to epigenetic changes and immunomodulatory effects that enhance the graft-versus-leukemia effect. There may be a risk of GVHD, and further exploration into pathophysiology and predisposing factors are warranted.