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WT1 mRNA in cerebrospinal fluid associated with relapse in pediatric lymphoblastic leukemia
Oscar Ramirez1, Adriana Linares, Marta Liliana Trujillo
1Cancer Unit, Fundación Clínica Valle del Lili, Cali, Colombia. osramire@hotmail.com
Insights
Detecting WT1 gene mRNA in cerebrospinal fluid (CSF) strongly predicts relapse in pediatric lymphoid precursor neoplasms. This finding offers a novel method for early detection of subclinical disease, improving patient monitoring.
Area of Science:
- Oncology
- Pediatric Hematology
- Molecular Diagnostics
Background:
- Assessing the relationship between WT1 gene mRNA detection in cerebrospinal fluid (CSF) and neoplastic relapse in pediatric patients with lymphoid precursor neoplasms.
- Investigating the utility of WT1 mRNA as a biomarker for relapse in pediatric leukemia.
Purpose of the Study:
- To determine if WT1 mRNA detection in CSF correlates with neoplastic relapse in pediatric patients undergoing treatment for lymphoid precursor cell neoplasms.
- To evaluate WT1 mRNA as a potential marker for subclinical disease detection in pediatric leukemia.
Main Methods:
- Included 94 pediatric patients (<19 years) with lymphoid precursor cell leukemia in remission.
- Analyzed CSF samples using cytology, cytochemistry, cell count, and qualitative RT-PCR during intrathecal chemotherapy.
- Monitored for clinical, radiologic, and cytologic evidence of CNS, hematologic, or other neoplastic relapses.
Main Results:
- WT1 mRNA was detected in CSF in 28.7% of patients during follow-up.
- A statistically significant association was found between WT1 detection in CSF and CNS relapse.
- Elevated hazard ratios for isolated hematologic relapse (5.04) and all relapse types (7.48) were observed.
Conclusions:
- WT1 mRNA detection in CSF is strongly associated with CNS and hematologic relapse in pediatric lymphoid precursor neoplasms.
- Despite a short follow-up potentially underestimating relapse incidence, WT1 mRNA shows promise for subclinical disease detection.
- This approach may offer a novel, valuable tool for monitoring pediatric leukemia patients.
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 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.