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

Purpose: To identify the long-term sequelae of therapy for malignant germ c ell rumors (GCTs). Patients and Methods: Between 1980 and 1998, 1,132 patients were prospectiv ely enrolled onto the German nontesticular GCT studies. A total of 442 pati ents received chemotherapy using combinations of the drugs cisplatin, ifosf amide, etoposide, vinblastine, and bleomycin, and 174 patients were treated with a combination of chemotherapy and radiotherapy. Median follow-up dura tion 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) o r 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 chemo therapy (three of 442) and 4.2% for patients treated with combined chemothe rapy and radiotherapy (three of 174). Notably, four of these six patients h erd been treated according to a standard protocol with modest cumulative ch emotherapy doses. Five patients had received less than 2 g/m(2) epipodophyl lotoxins, and four patients had received less than 20 g/m(2) ifosfamide. Fo ur patients presented with AML, two with myelodysplasia in transformation t o AML, In five patients, cytogenetic aberrations were found, four of which were considered characteristic for t-AML, Four patients died despite antile ukemic 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 pathogene tic mechanisms must be considered. AML might evolve from a malignant transf ormation of GCT components without any influence of the chemotherapy. On th e other hand, the use of alkylators and topoisomerase It inhibitors is asso ciated with an increased risk of t-AML. Future studies will show if the red uction of treatment intensity in the current protocol reduces the risk of s econdary leukemia in these patients. (C) 1999 by American Society of Clinic al Oncology.