4115 POSTER Thiopurine-S-Methyl-Transferase Gene Polymorphisms and Antimetabolite Drug Toxicity in Children Treated for Acute Leukemia and Non-Hodgkin's Lymphoma

Abstract

Background: Reliable response criteria are still lacking in stage 4 neuroblastomas. We hypothesized that the dynamics of BM clearing mirrors the response to cytotoxic treatment and is thus able to identify prognostically differing subgroups of stage 4 patients. Patients and Methods: BM samples from 81 stage 4 patients registered in two neuroblastoma Trials were tested with a fully automatic fluorescence based device combining GD2 based immunocytology and molecularcytogenetic analyses of identical cells (automatic immunofluorescence plus FISH, AIPF). 44 patients (age 0 to 239 months, 219 BM specimens, median observation time 8.2 years) met the inclusion criteria (BM specimens at diagnosis and given time points during treatment and genomic information on the primary tumour) with a complete data set. Results: BM clearing after 2 to 4 chemotherapy cycles was achieved by 28 patients (63.6%) and was significantly associated with overall survival (OS) in patients above 18 months at diagnosis (p < 0.0002, Logrank test) but not in the younger age group. Stage 4 patients below 18 months had a good prognosis irrespective of BM clearing and tumour genetics. In younger patients, none of the genetic markers showed a correlation with OS. MNA was associated and intact 11q showed a trend towards association with BM clearing (p < 0.3 and p = 0.0735, both Fisher’s Exact Test). Conclusion: The determination of BM clearance reaches the so far highest prognostic impact in stage 4 neuroblastoma patients over 18 months of age making accurate BM monitoring an important tool for risk assessment in this patient group.