Acute myelogenous leukemia after treatment for malignant germ cell tumors in children.

Abstract

To identify the long-term sequelae of therapy for malignant germ cell tumors (GCTs). 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). 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/m(2) epipodophyllotoxins, and four patients had received less than 20 g/m(2) 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. 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.