title: Increased risk of secondary leukemia after single-agent treatment with etoposide for Langerhans' cell histiocytosis.
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 leukemogenic 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.
authors: Division of Pediatric Hematology/Oncology, G. Gaslini Children's Hospital, Genoa, Italy.
authors: R
authors: R
authors: Haupt
authors: T R
authors: TR
authors: Fears
authors: P
authors: P
authors: Rosso
authors: R
authors: R
authors: Colella
authors: G
authors: G
authors: Loiacono
authors: M
authors: M
authors: de Terlizzi
authors: A
authors: A
authors: Mancini
authors: A
authors: A
authors: Comelli
authors: P
authors: P
authors: Indolfi
authors: A
authors: A
authors: Donfrancesco
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D011241:Prednisone / Q000008:administration & dosage; D012306:Risk; D016879:Salvage Therapy; D014747:Vinblastine / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone