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Treatment of acute promyelocytic leukemia in children: arsenic or ATRA

Leukemia volume 18, pages 1576–1577 (2004)Cite this article

This invited commentary is addressed at the paper by George et al1 on ‘treatment of childen with Acute Promyelocytic Leukemia with arsenic trioxide –’published in this issue of Leukemia. Acute Promyelocytic Leukemia (APL) is a unique disorder, characterized by a translocation involving the PML gene on chromosome 15 and the retinoic acid receptor – RARα- gene on chromosome 17 giving rise to the classic translocation t(15;17)(q22;q21) and the PML-RARα fusion protein.2 Less frequent are associations of RARα with PLZF on chromosome 11 giving rise to t(11;17)(q23;q21)3 and the NPM gene on chromosome 5 giving rise to t(5;17)(q35;q21);4 rarely t(15;17) may not directly involve RARα as in t(15;17)(q13;q12).5 Morphologic variants include the microgranular variant (M3v) and the agranular variant. All of these cytogenetic and morphologic variants have been described in children as well as in adults and thus from a cytogenetic and morphologic perspective the disease appears to be homogeneous in adults and children.6 Yet some clinical differences have been observed, for example, high white counts and the M3v variant appears to be more common in children;7, 8, 9 and internal tandem duplication of the receptor tyrosine kinase FLT3 (FLT3-ITD) is less common in childhood.10 While the overall outcome with ATRA-based regimens appears to be the same, there is an increased incidence of headaches and the more ominous pseudotumor cerebri in children with ATRA.9 Additional concerns with current APL therapies for children are the risks for cardiotoxicity (acute and delayed) associated with the high cumulative doses of anthracyclines (up to 600 mg/M2 of daunorubicin) included in the chemotherapy component of some of the combined adult-pediatric APL studies. Thus, further improvements are necessary in the therapy of APL in children.

In this issue of the journal, Dr George et al1 from Vellore, India, describe their experience in 11 children with newly diagnosed APL treated with arsenic trioxide (As2O3), with virtually no additional chemotherapy. The age ranged from 6 to 14 years and all had molecular documentation of PML-RAR. None of the children had had WBC>10 000/μl, a well-recognized poor prognostic indicator in APL and none had evidence of coagulopathy prior to treatment. Treatment consisted of eight cycles of As2O3 at a dose of 0.15 mg/kg/day as an i.v. infusion over 4 h. During induction As2O3 was administered until the remission was achieved or a maximum of 60 days. Six patients also had hydroxyurea (HU) because of increasing white count and one patient in addition received a single dose of mitoxantrone. The mean duration to achieve remission was 48 days (41–60). One patient died on day 5 of intracranial hemorrhage and the remainder achieved remission. At the time of report, eight patients were off therapy and two were still on primary treatment. One patient had relapsed 6 months after completion of therapy and responded to a second course of arsenic trioxide. With a median duration of follow-up of 30 months (range 3–60), the leukemia free-survival was 81% with an overall survival of 91%. There were no cases of ATRA syndrome or pseudo-tumor cerebri. Minor toxicities included hyperpigmentation of the skin, ichthyosis, mild reversible peripheral neuropathy in one patient. Significant cardiotoxicity was not observed but it is not clear if the children were monitored by electrocardiograms for prolonged QT intervals.

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Authors and Affiliations

  1. Children's Hospital of Michigan and Wayne State University School of Medicine, Detroit, MI, USA

    Y Ravindranath

  2. Hackensack University Medical Center and University of Medicine and Dentistry, New Jersey, Hackensack, NJ, USA

    J Gregory

  3. University of California-San Francisco and Children's Hospital of Oakland, Oakland, CA, USA

    J Feusner

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  1. Y Ravindranath
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  2. J Gregory
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  3. J Feusner
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Correspondence to Y Ravindranath.

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Ravindranath, Y., Gregory, J. & Feusner, J. Treatment of acute promyelocytic leukemia in children: arsenic or ATRA. Leukemia 18, 1576–1577 (2004). https://doi.org/10.1038/sj.leu.2403479

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