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.


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 RT-PCR 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 follow-up 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.
Ramirez
Oscar
O
Cancer Unit, Fundación Clínica Valle del Lili, Cali, Colombia. osramire@hotmail.com
Linares
Adriana
A
Trujillo
Marta Liliana
ML
Caminos
Jorge Eduardo
JE
D002648:Child; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000134:cerebrospinal fluid* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000235:genetics; D012333:RNA, Messenger / Q000134:cerebrospinal fluid*; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D025721:WT1 Proteins / Q000235:genetics*
D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025721:WT1 Proteins