Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

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