Adding Venetoclax to the High-dose Chemotherapy Regimen Prior to Mismatche Allogeneic Stem Cell Transplant

Inclusion Criteria:

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