WT1 mRNA in cerebrospinal fluid associated with relapse in pediatric lymphoblastic leukemia

Background: The goal was to assess a possible relationship between the detection of mRNA from WT1 gene in cerebrospinal fluid (CSF) and neoplastic relapse in pediatric patients being treated for lymphoid precursor cell neoplasms. Patients and Methods: Ninety-four patients less than 19 years old with lymphoid precursor cell leukemia in hematologic remission and without central nervous system (CNS) compromise were included. Cytology, cytochemistry, cell count, and qualitative RTPCR were performed using routine CSF samples obtained during intrathecal chemotherapy administration. The main outcome measure was clinical, radiologic, and cytologic evidence of CNS, hematologic or any other type of neoplastic relapse. Results: At some time during follow-up, 28.7% of the patients had a positive WT1 CSF test. Relapses included 10 patients with isolated hematologic, 4 with isolated CNS, 1 with combined CNS and hematologic, and 1 with mediastinal relapse; the maximal followup period was 312 days. A statistically significant association was found between the detection of WT1 in CSF and CNS relapse. Adjusted hazard rate ratios of 5.04 (95% confidence interval 1.33 - 19.12) and 7.48 (2.34-23.93) were estimated for isolated hematologic relapse and for all types of relapses, respectively. Conclusions: Although it is likely that the short follow-up period underestimated the incidence of relapse, this study was able to identify a strong association between WT1 mRNA detection and CNS or hematologic relapse. These findings represent a potentially novel and useful approach for subclinical disease detection.