Increased Risk of Secondary Leukemia After Single-Agent Treatment with Etoposide for Langerhans' Cell Hlstlocytosls

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Abstract
The study evaluated 139 patients diagnosed with Langerhans' cell histiocytosis (LCH) and enrolled in any protocol of the Italian Association of Pediatric Hematology/Oncology since 1982, Treatment was etoposide (VP-16) only in 50 patients, VP-16 and other drugs with an already established bukemogenic effect in 17 patients, only drugs with leukemogenic effect in 6 patients, other drugs in 35 patients, and surgery only in 31 patients. Median length of follow-up after diagnosis was 65 months (range, 1 to 126 months) for a total of 742.5 person-years at risk (PYRs). Three cases of acute myelogenous leukemia (AML) were reported; only 0.0044 case was expected. The standard incidence ratio (SIR) of AML in this cohort was 680.5 [95% confidence interval (CI), 140.2–1988.5], and the incidence rate per 1000 PYRs was 4.0 (95% CI, 0.8–11.8). For the subgroup treated with single-agent VP-16, the SIR after treatment was 2270.0 (95% CI, 275–8199), and the incidence rate after treatment was 14.7 (95% CI, 1.8–42.8). The study confirms a higher risk of leukemia after LCH and supports the hypothesis of an association between treatment-related acute nonlymphocytic leukemia and single-agent treatment with VP-16.

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