ACUTE MYELOID-LEUKEMIA IN PATIENTS TREATED FOR RHABDOMYOSARCOMA WITH CYCLOPHOSPHAMIDE AND LOW-DOSE ETOPOSIDE ON INTERGROUP RHABDOMYOSARCOMASTUDY .3. AN INTERIM-REPORT

The early occurrence of five cases of acute myeloid leukemia (AML) in children treated for primary rhabdomyosarcoma on the Intergroup Rhabdo myosarcoma Study III (IRS III) has prompted this report. These patient s received cyclophosphamide and four received etoposide in addition to other agents. There were 1,062 eligible patients entered on IRS III b etween 1984 and 1991. Following surgery, treatment consisted of multia gent chemotherapy and radiotherapy in select clinical groups. Median f ollow-up time is 3.7 years (range 0-7.4 years). Incidence densities an d odds ratios for AML were calculated for various treatment groups. Fi ve cases of secondary AML have been reported through August 1992. A si ngle case of osteogenic sarcoma was reported in the same period and a patient with myelodysplastic syndrome has occurred since that time. Me dian time to development of AML was 39 months. Incidence density of AM L for patients receiving neither cyclophosphamide nor etoposide was 0, for those receiving cyclophosphamide but no etoposide it was 7.6, and when both agents were given, it was 51.6. The odds ratios of AML for the latter two groups indicated a risk of AML which was seven times hi gher in the patients who received both agents. A history of breast can cer was present in all five families of patients with AML and several other cancers had occurred in three families. Preliminary analysis sug gests a possible causal role for low-dose etoposide in addition to tha t assumed for cyclophosphamide in the early development of AML among p ediatric patients treated for rhabdomyosarcoma. (C) 1994 Wiley-Liss, I nc.