Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

For patients with newly diagnosed disease: diagnosis of "high-risk" myelodysplastic syndrome (MDS) (\>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 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 standard criteria requiring first or subsequent salvage therapy; patients with biphenotypic AML 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

Treatment-related mortality (TRM) score =\< 6.9 as calculated with simplified model

The use of hydroxyurea prior to study registration is allowed; patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) \> 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m\^2/dose) prior to enrollment

For patients with relapsed/refractory disease: patients may have previously received chemotherapy with a mitoxantrone- or cladribine-based regimen for MDS or AML; if that patient has received G-CLAM before and has been sensitive to this regimen, eligibility will be determined on a case-by-case basis by the study principal investigator (PI)

Should be off any active systemic 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

Bilirubin =\< 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)

Serum creatinine =\< 2.0 mg/dL (assessed within 14 days prior to study day 0)

Left ventricular ejection fraction \>= 45%, assessed within 3 months prior to study day 0, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographic suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal

Women of childbearing potential and men must agree to use adequate contraception

Provide written informed consent

What this study is about