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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Acute Promyelocytic Leukemia

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Arsenic trioxide has also been identified as an active agent in patients with APL, and there are now data for its use as induction therapy, consolidation therapy, and in the treatment of patients with relapsed APL:

  • For adults with relapsed APL, approximately 85% achieve morphologic remission following treatment with this agent.[40,41,42] Arsenic trioxide is well tolerated in children with relapsed APL. The toxicity profile and response rates in children are similar to that observed in adults.[43]
  • In adults with newly diagnosed APL, the addition of two consolidation courses of arsenic trioxide to a standard APL treatment regimen resulted in a significant improvement in EFS (80% vs. 63% at 3 years, P < .0001) and disease-free survival (90% vs. 70% at 3 years, P < .0001), although the outcome of patients who did not receive arsenic trioxide was inferior to the results obtained in the GIMEMA or PETHEMA trials.[44] The Children's Oncology Group is evaluating arsenic trioxide as a consolidation therapy for newly diagnosed children with APL.
  • The concurrent use of arsenic trioxide and ATRA in newly diagnosed patients with APL results in high rates of CR.[45,46,47] Early experience in children with newly diagnosed APL also shows high rates of CR to arsenic trioxide, either as a single agent or given with ATRA. Results of a meta-analysis of seven published studies in adult APL patients suggest that the combination of arsenic trioxide and ATRA may be more effective than arsenic trioxide alone in inducing CR.[48] The impact of arsenic induction (either alone or with ATRA) on EFS and OS has not been well characterized and will require larger randomized studies. [49,50]
  • Arsenic trioxide was evaluated as a component of induction therapy with idarubicin and ATRA in the APML4 clinical trial, which enrolled both children and adults (N = 124 evaluable patients).[20] Patients received two courses of consolidation therapy with arsenic trioxide and ATRA (but no anthracycline) and maintenance therapy with ATRA, 6-mercaptopurine, and methotrexate. The 2-year rate for freedom from relapse was 97.5%, failure-free survival (FFS) was 88.1%, and OS was 93.2%. These results are superior for FFS and freedom from relapse when compared with the predecessor clinical trial (APML3) that did not use arsenic trioxide.

Because arsenic trioxide causes QT interval prolongation that can lead to life-threatening arrhythmias (e.g., torsades de pointes),[51] it is essential to monitor electrolytes closely in patients receiving arsenic trioxide and to maintain potassium and magnesium values at midnormal ranges.[52]

The induction and consolidation therapies currently employed result in molecular remission as measured by reverse transcriptase–polymerase chain reaction (RT–PCR) for PML-RARA in the large majority of APL patients, with 1% or fewer showing molecular evidence of disease at the end of consolidation therapy.[14,31] While two negative RT-PCR assays after completion of therapy are associated with long-term remission,[53] conversion from negative to RT-PCR positivity is highly predictive of subsequent hematologic relapse.[54] Patients with persistent or relapsing disease based upon PML-RARA RT-PCR measurement may benefit from intervention with relapse therapies (refer to the Recurrent Acute Promyelocytic Leukemia (APL) subsection of the Recurrent Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies section of this summary for more information).

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WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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