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Acute Myelogenous Leukemia After Treatment for Malignant Germ Cell Tumors in Children

From the Department of Pediatric Hematology and Oncology, Heinrich-Heine-University Düsseldorf, Medical Center, Düsseldorf; Department of Pediatrics, Charité, Humbold-University, Berlin; Department of Pediatrics, Johann Wolfgang Goethe University, Frankfurt/Main; Department of Pediatrics, University of Ulm, Ulm, Germany; and Department of Pediatrics, St Anna Spital, Vienna, Austria.

Address reprint requests to Dominik T. Schneider, MD, Department of Pediatric Hematology and Oncology, Heinrich-Heine-University, Medical Center, Moorenstr.5, D-40225 Düsseldorf, Germany; email dominik.schneider{at}uni-duesseldorf.de

PURPOSE: To identify the long-term sequelae of therapy for malignant germ cell tumors (GCTs).

PATIENTS AND METHODS: Between 1980 and 1998, 1,132 patients were prospectively enrolled onto the German nontesticular GCT studies. A total of 442 patients received chemotherapy using combinations of the drugs cisplatin, ifosfamide, etoposide, vinblastine, and bleomycin, and 174 patients were treated with a combination of chemotherapy and radiotherapy. Median follow-up duration was 38 months (range, 6 to 199 months).

RESULTS: Six patients developed therapy-related acute myelogenous leukemia (t-AML). There was no t-AML among patients treated with surgery (n = 392) or radiotherapy only (n = 124). The Kaplan-Meier estimates of the cumulative incidence (at 10 years) of t-AML were 1.0% for patients treated with chemotherapy (three of 442) and 4.2% for patients treated with combined chemotherapy and radiotherapy (three of 174). Notably, four of these six patients had been treated according to a standard protocol with modest cumulative chemotherapy doses. Five patients had received less than 2 g/m² epipodophyllotoxins, and four patients had received less than 20 g/m² ifosfamide. Four patients presented with AML, two with myelodysplasia in transformation to AML. In five patients, cytogenetic aberrations were found, four of which were considered characteristic for t-AML. Four patients died despite antileukemic therapy. One patient is alive but suffered a relapse of his GCT, and one patient is alive and well. No secondary solid neoplasm was observed.

CONCLUSION: In patients with AML after treatment for GCT, several pathogenetic mechanisms must be considered. AML might evolve from a malignant transformation of GCT components without any influence of the chemotherapy. On the other hand, the use of alkylators and topoisomerase II inhibitors is associated with an increased risk of t-AML. Future studies will show if the reduction of treatment intensity in the current protocol reduces the risk of secondary leukemia in these patients.

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