Decitabine With GCLAM for Adults With Newly Diagnosed, Relapsed, or Refractory AML or High-Risk MDS

Inclusion Criteria: * For patients with newly diagnosed disease: diagnosis of "high-grade" MDS (\>= 10% blasts by morphology) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; for patients with relapsed/refractory disease: prior diagnosis of "high-risk" MDS or non-APL AML, with relapsed/refractory disease according to 2003 recommendations of the International Working Group, requiring first or subsequent salvage therapy; patients with mixed phenotype acute leukemia (MPAL) are eligible * Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines * Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents * Treatment-related mortality (TRM) score =\< 9.2 as calculated with simplified model * Should be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved * May have previously received monotherapy with demethylating agents for MDS o…