Arsenic induces acute promyelocytic leukemia remission

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By Lynda Williams, Senior medwireNews Reporter

Elderly patients with acute promyelocytic leukemia (APL) have a high rate of response to arsenic trioxide (ATO), say researchers who believe the drug should be a first-line treatment in this population.

Treatment with ATO alone resulted in complete hematologic remission for 87.9% of 33 patients aged 60 years and older with de novo APL, report Jin Zhou and co-workers from Harbin Medical University in Heilongjiang, China.

Indeed, 28 patients continued with postremission ATO and, over a median of 99 months' follow up, achieved a 10-year incidence of relapse, overall survival, disease-free survival, and cause-specific survival of 10.3%, 69.3%, 64.8%, and 84.8%, respectively.

This survival rate compares favorably with that of younger patients who may be successfully treated with all-trans retinoic acid and anthracycline-based chemotherapy, the team suggests.

Writing in Cancer, Zhou et al note the "characteristic leukocytic response" to ATO, such as an early increase in white blood cell count (WBC), followed by neutropenia and then WBC recovery.

"Based on decades of our clinical observations, the treatment response can be found in more than 90% of patients with APL, whereas it never occurred in the cases with other diseases, suggesting that the characteristic leukocytic response to ATO induction is highly sensitive and specific and may serve as a further validation of the diagnosis of APL," the team comments. "In fact, this response was observed in all but 3 patients in this series."

During induction of remission treatment (0.16 mg/kg per day up to a maximum of 10 mg/day), the most common adverse effect was leukocytosis, affecting 63.6% of patients. Five patients with severe leukocytosis developed definite differentiation syndrome and this was treated successfully with steroids and temporary withdrawal of ATO.

Patients with complete hematologic remission continued ATO treatment on an outpatient basis with close WBC monitoring over 4 years. Adverse events were "mild, transient, and no treatment was required," the researchers say.

No evidence of chronic arsenicosis, such as liver or kidney damage, or skin changes, were reported, and arsenic levels in the nails, hair, and urine did not differ from untreated controls.

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