Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy

Abstract

Secondary neoplasms (SNs) represent serious late complications after successful treatment of malignant diseases. To evaluate the rate and type of SNs after Berlin-Frankfurt-Münster (BFM) treatment in children with acute lymphoblastic leukemia (ALL), we analyzed the data from the BFM database and the German Childhood Cancer Registry (GCCR). Between April 1979 and April 1995, 5006 children with B-precursor or T-ALL were enrolled in 5 ALL-BFM multicenter trials. The median follow-up time from diagnosis was 5.7 years (range 1.5-18 years). By December 1997, 52 SNs were documented, including 16 acute myeloid leukemias (AMLs), 13 neoplasms of the central nervous system (CNS), and 23 other neoplasms. Compared with the expected numbers estimated from incidence rates derived from the GCCR, this represented a 14-fold increase for all cancers and a 19-fold increase for CNS tumors. SNs developed 0.9 to 15 years (median: 6 years) after the diagnosis of ALL; 46 patients were in first complete remission (CR). The overall cumulative risk of SNs at 15 years was 3.3% (95% confidence interval [CI]: 1.6%-5.1%) and 2.9% (95% CI: 1.6%-4.2%) in first CR. The risk was 3.5% (95% CI: 1.5%-5.5%) after treatment, including cranial irradiation and significantly lower in nonirradiated patients: 1.2% (95% CI: 0.2%-2.3%;P = .048). The development of secondary AML was not associated with the use of any specific cytotoxic agent. Considering the high-survival rate of this large unselected ALL cohort, the risk of SN is relatively low, though higher, especially after cranial irradiation, than in the general population. Long-term follow-up is mandatory, and further SNs with longer latency periods are to be expected.