Inclusion Criteria:

* Patients must be newly diagnosed with a clinical diagnosis of APL (initially by morphology of bone marrow or peripheral blood)

* Bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted
* If the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate the PML-RARalpha transcript by RQ-PCR to be eligible
* NOTE: A lumbar puncture is not required in order to be enrolled on study nor are lumbar punctures recommended at the time of diagnosis; if the diagnosis of APL is known or suspected, diagnostic lumbar punctures in patients with neurologic symptoms should be deferred until any coagulopathy is corrected; if central nervous system (CNS) disease is suspected or proven, a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma; if CNS disease is documented, patients are still eligible and will receive protocol directed intrathecal treatments
* Patients may receive up to a maximum of 5 days of pre-treatment with ATRA prior to administration of protocol therapy
* Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine prior to beginning protocol directed therapy is allowed; however, it should be noted that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not recommended
* All patients and/or their 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 studies must be met

Exclusion Criteria:

* Patients with secondary APL are excluded; this includes all patients with APL that may have resulted from prior treatment (chemotherapy or radiation)
* Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) but without evidence of APL by bone marrow or peripheral blood morphology are excluded
* Patients with a pre-existing diagnosis of a prolonged QT syndrome (even if corrected QT interval \[QTc\] is normal at the time of APL diagnosis) are excluded
* Patients with a baseline QTc of \> 450 msec are excluded; Bazett's formula is to be used for measurement of the corrected QT interval: the QT interval (msec) divided by the square root of the RR interval (msec)
* Patients with a history or presence of significant ventricular or atrial tachyarrhythmia are excluded
* Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded
* Patients with serum creatinine \> 3.0 mg/dL and patients on active dialysis for renal dysfunction are excluded
* Patients who have received treatment with any other cytotoxic chemotherapy prior to beginning protocol therapy (other than allowed in above criteria) are excluded
* Female patients who are pregnant are excluded; patients should not be pregnant or plan to become pregnant while on treatment; a pregnancy test prior to enrollment is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are excluded
* Sexually active patients of reproductive potential who have not agreed to be abstinent or use 2 forms of effective contraception during treatment through 1 month off therapy are excluded