Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome

Inclusion Criteria:

* Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization \[FISH\])
* Patient has one of the following:

  * Patient has previously untreated de novo AML and meets the criteria for AML with \>= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification

    * Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/FISH testing is feasible can be substituted for the marrow exam at diagnosis
  * Patient has cytopenias and/or bone marrow blasts but does not meet the criteria for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of \< 20% marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome (MDS)
  * For patients who do not meet criteria for AML or MDS as outlined above; patient has a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention and:

    * Is \> 8 weeks since resolution of transient myeloproliferative disease (TMD) with \>= 5% blasts, OR
    * Has an increasing blast count (\>= 5%) in serial bone marrow aspirates performed at least 4 weeks apart
* Children who have previously received chemotherapy, radiation therapy or any anti-leukemic therapy are not eligible for this protocol, with the exception of cytarabine for the treatment of TMD
* There are no minimal organ function requirements for enrollment on this study

  * Note: Previous cardiac repair with sufficient cardiac function is not an exclusion criteria
* Each patient's parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human subjects research must be met

Exclusion Criteria:

* Patients with promyelocytic leukemia (French-American-British \[FAB\] M3)
* Prior therapy

  * Patients =\< 30 days from the last dose of cytarabine used for treatment of TMD