This phase II trial studies how well azacitidine works in treating patients with relapsed myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who have undergone stem cell transplant. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. To improve overall survival in patients with post-transplant relapse of myeloid malignancies.

OUTLINE:

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

• MDS, CMML or AML patients (as diagnosed by World Health Organization [WHO] criteria) with evidence of relapse or progression at >= day 28 and < day 100 post-transplant
• Recurrent or increased cytogenetic abnormalities by standard karyotype or fluorescence in situ hybridization (FISH) (the cytogenetic abnormalities must have been previously documented at some time point between diagnosis and date of stem cell transplant)
• Morphologic evidence of recurrence or increased abnormal myeloblasts in peripheral blood or marrow
• Flow Cytometric evidence of disease as determined by recurrent or increased abnormal myeloblasts in peripheral blood or marrow
• Extramedullary relapse (local radiotherapy will be allowed)
• MDS, CMML, or AML patients with persistent stable disease or persistent disease with regression at >= day 28 and < day 100 post-transplant; the inclusion of patients with persistent stable or persistent regressing disease in this protocol is not meant to advocate treatment; however, if the attending physician is inclined to offer treatment then these patients would be eligible for this study
• Persistence of cytogenetic abnormalities by standard karyotype or FISH
• Persistent morphologic evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow
• Persistent flow cytometric evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow
• Extramedullary persistence or regression

Exclusion Criteria:

• Refractory disease at time of stem cell transplant; patients who received chemotherapy prior to transplant with no evidence of response by International Working Group (IWG) criteria
• >= 10% bone marrow myeloblasts as measured by morphology
• Evidence of central nervous system (CNS) disease at time of relapse by morphology or flow (a diagnostic lumbar puncture [LP] is not required at time of relapse)
• Serum creatinine > 2 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2x ULN
• Performance status > 2 (Eastern Cooperative Oncology Group [ECOG] Scale)
• Patients with severe disease other than MDS, CMML or AML which would be expected to prevent compliance with treatment
• Patients with severe infections (pneumonia, sepsis, etc) within the 2 weeks prior to the anticipated start of protocol treatment