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Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity

Leukemia volume 20, pages 881–883 (2006)Cite this article

The efficacy of arsenic trioxide (As2O3) in the treatment of newly diagnosed and relapsed acute promyelocytic leukemia (APL) has been well established.1 Unlike all-trans retinoic acid (ATRA), which though effective as a single agent fails to induce molecular remission, single agent As2O3 can induce molecular remission consistently in the majority of patients.1 Arsenic trioxide is well tolerated and is not associated with conventional toxicities of chemotherapy such as grade 3/4 mucositis and neutropenia. These advantages have resulted in single agent As2O3 replacing ATRA, chemotherapy or a combination of ATRA and chemotherapy in the treatment of patients with relapsed APL.1 Concerns have been raised about the potential for fatal cardiac and hepatic toxicity1 in a subset of patients with APL who were treated with As2O3. However, most of these toxicities have been described in patients with relapsed APL who had received multiple courses of chemotherapy and had significant comorbidity. There are limited data on the toxicity profile of As2O3 and its impact on clinical outcomes when used in the treatment of patients with newly diagnosed APL who do not have significant comorbid conditions.

It has been noted that there is considerable interindividual variation in susceptibility to As2O3-induced toxicity, which is probably related to differences in in vivo biotransformation of arsenic. In addition to a poorly characterized arsenic methyltransferase, a number of other enzyme systems and genetic polymorphisms have been shown to have an effect on arsenic methylation.2 Of these, polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene and those of the glutathione S-transferases (GST) family of proteins have been noted to have an impact on the metabolism and toxicity profile of inorganic arsenic.3, 4 We report the hepatotoxicity profile in a cohort of patients with newly diagnosed APL treated at our center, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity.

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  1. Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India

    V Mathews, S Desire, B George, K M Lakshmi, J G Rao, A Viswabandya, A Bajel, A Srivastava & M Chandy

  2. Cytogenetics Unit, Christian Medical College, Vellore, Tamil Nadu, India

    V M Srivastava

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  1. V Mathews
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Mathews, V., Desire, S., George, B. et al. Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity. Leukemia 20, 881–883 (2006). https://doi.org/10.1038/sj.leu.2404165

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