Patients eligible for a mismatch allogeneic stem cell transplant will receive Venetoclax daily for 7 days prior to transplant in addition to the following chemotherapy regimen: Decitabine daily for 5 days, Fludarabine daily for 5 days, and Busulfan daily for 2 days followed by 1 day of total body irradiation. Stem cell transplant will occur thereafter.
Availability of a 4/8 - 6/8 HLA-matched related donor or a 7/8 HLA-matched unrelated donor Receiving first allogeneic transplant KPS >/= 70% MDS associated with TP53 mutation AND R-IPSS high or very high risk at diagnosis OR AML with adverse risk cytogenetics or molecular abnormalities according to the 2017 ELN risk stratification OR pre-transplant MRD by either flow cytometry, cytogenetics or FISH Less than 5% myeloblasts in the marrow pre-transplant
Exclusion Criteria:
Poor cardiac function defined as LVEF <45% Poor pulmonary function defined as FEV1, FVC, or DLCO <50% predicted Poor liver function defined as bilirubin >/=2.5mg/dL, AST/ALT >3xULN Poor renal function defined as creatinine >/=2.0mg/dL or CrCl <40mL/min Ongoing or active systemic infection, active Hepatitis B or C virus infection, or known HIV positivity Patient requiring treatment with a moderate or strong inhibitor or inducer of CYP3A4 or a P-gp inhibitor within 7 days prior to starting preparative chemotherapy through Day +4 post-transplant