A Phase 2 Study of Allogeneic Stem Cell Transplant in Myelodysplastic Syndrome Following Conditioning With Fludarabine and Total Body Irradiation 800 cGy

This is a single center phase II study of allogeneic stem cell transplantation in MDS who are unlikely to benefit from conventional therapy. Patients will undergo standard allogeneic stem cell transplant protocol following standard Flu/TBI 800 conditioning, PBSC transplant, and GVHD prophylaxis with PTCy and tacrolimus.

Inclusion Criteria: * MDS diagnosis and: * Very low, low, or low-intermediate risk by IPSS-M. This can be determined using the online calculator: https://mds-risk-model.com/. Must be relapsed, refractory or ineligible (due to serum erythropoietin level \>500 U/L) for erythropoiesis stimulating agent (ESA). Prior luspatercept or imetelstat is permitted. Transfusion-dependent requiring \>4 units packed red blood cells (PRBCs) over an 8 week period during the 16 weeks before enrollment. or * TP53 mutation/deletion with combined VAF \< 50% * Meets standard criteria for allogeneic stem cell transplant * Patient and related Donor (if applicable) must sign the Informed Consent Form for the study. If donor is unrelated, donor does not sign Informed Consent Form and this will not affect recipient study eligibility * Patient is deemed suitable to receive Flu/TBI 800 conditioning regimen as standard of care transplant. Exclusion Criteria: * Prior therapy with hypomethylating agent * Prior autologous or allogeneic stem cell transplant