Inclusion Criteria:

- Patients must have one of the following disease characteristics:

- Therapy-related myeloid neoplasm (t-MN) age >= 18 years

- Patients must have received cytotoxic chemotherapy, radiation, or a drug
known to affect the properties of deoxyribonucleic acid (DNA) or cell
growth, prior to current diagnosis of therapy-related myeloid neoplasm
(t-MN); this broad definition is meant to include any prior therapy with
chemicals that affect DNA replication, DNA integrity, or DNA structure, or
chemicals that alter cell growth; this includes traditional cytotoxic
chemotherapy, newer immunologic agents that have been shown to have
cytotoxic activities in addition to immunosuppressive functions, and other
chemicals; note that patients with primary AML could be diagnosed with a t-
MN if morphology/cytogenetic analysis clearly indicated that the second
process is not a relapse of the original disease

- AML arising from an antecedent hematological disorder age >= 18 years

- De novo AML in patients age >= 60 years

- Relapsed and/or refractory AML >= 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment

- Male and female patients must use an effective contraceptive method during the study
and for at least 6 months after study treatment

- Patients must be at least 2 weeks from major surgery, radiation therapy,
participation in other investigational trials and must have recovered from clinically
significant toxicities of these prior treatments

- Ability to understand and willingness to sign the informed consent form

Exclusion Criteria:

- Concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified
in this protocol

- Diagnosis of acute promyelocytic leukemia (APL)

- Use of investigational agents/any anticancer therapy within 2 weeks before study
entry with the exception of hydroxyurea (note: for patients with hyperleukocytosis
[white blood cell (WBC) > 20,000/uL], hydroxyurea [and leukapheresis, if clinically
indicated] will be initiated and these patients will receive 5-azacytidine when the
WBC count has decreased to =< 20,000/uL; hydroxyurea can be overlapped with
5-azacytidine in selected cases, after consultation with the study chair; hydroxyurea
must be discontinued before the initiation of the HiDAC/mitoxantrone chemotherapy)

- Prior treatment with 5-azacytidine followed immediately by HiDAC and mitoxantrone as
proposed in this study (note: prior therapy with 5-azacytidine or decitabine or HiDAC
or mitoxantrone would be allowed-in patients with relapsed/refractory disease- unless
the prior therapy was identical to the schema/schedule proposed in this study)

- Active second cancer other than specified; active cancer refers to cancer that
requires systemic chemotherapy or biological therapy within 6 months of the study
entry; patients who have received only hormonal therapy in the neoadjuvant or
adjuvant setting in the past 6 months may participate in this study

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction (e.g. uncontrolled or severe cardiovascular disease, diabetes, pulmonary
disease, infection, psychiatric illness) that may in the judgment of the treating
physician/ principal investigator place the patient at undue risk to undergo
treatment

- Pregnant or lactating patients

- Any significant concurrent illness that would, in the judgment of the treating
physician/principal investigator, compromise patient safety or compliance, or study
participation