BackgroundMyelofibrosis (MF) is a myeloproliferative neoplasm with a relapse rate of 10-30% after allogeneic transplantation (alloHCT). Current recommendations to treat relapse include withdrawal of immunosuppression, donor lymphocyte infusion, and potentially a second alloHCT. Hypomethylating agents (HMA) have shown efficacy as salvage therapy by inducing an immune response and improving donor chimerism for myeloid neoplasm post-HCT. Data is limited on use of HMA for MF post-alloHCT relapse. ObjectiveTo determine the benefit of using HMA for MF patients relapsing after alloHCT. Study DesignWe retrospectively analyzed 12 patients with MF post-alloHCT relapse who received HMA to determine response via restoration of donor chimerism and clearance of molecular mutation. ResultsThe median age was 61 years (range 41-72) with 92% classified as intermediate-2/high-risk by DIPSS and 83% as high/very high risk by MIPSS70+. The median time to relapse post-alloHCT was 282.5 days (range 96-2388) with median donor chimerism 57.82% (range 2.48-84) prior to starting HMA. After two cycles of HMA, 58% experienced restoration of donor chimerism. Molecular clearance of pre-HCT driver mutations occurred in 50% of patients at the most recent follow-up. New chronic GvHD occurred in 50% of patients with most being mild to moderate that resolved after treatment. ConclusionHMA was safe and effective in a high-risk population after post-alloHCT relapse and is an option for patients in the future.