Pediatric NHL Clinical Trial
Official title:
A Retrospective Cohort Study: The Influence of MTHFR C677T and A1298C on the High-dose Methotrexate-Related Toxicities in Pediatric Patients With Non-Hodgkin Lymphoma
We hypothesized that polymorphism MTHFR C677T and A1298C should be associated with HD-MTX-related toxicities in children with NHL. Therefore, we aimed to retrospectively explore their relationships in this analysis.
INTRODUCTION: Non-Hodgkin lymphoma (NHL), the fourth most common malignancy across the
pediatric age spectrum, is a heterogeneous group of lymphoid malignancies. In children, NHL
comprises four main wide categories: lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL),
diffuse large B-cell lymphoma (DLBCL), and anaplastic large cell lymphoma (ALCL). The current
overall survival rate of pediatric NHL exceeds 80% due to dramatic progress in developing
risk-adapted curative therapy (1), in which methotrexate (MTX) plays a crucial part.
MTX is used to treat a variety of cancers. A high-dose MTX (HD-MTX) regimen, referred to the
administration of a dosage ranging from 0.5g/m2 to 12.0g/m2 or even higher, is commonly used
to treat childhood acute lymphoblastic leukemia (ALL), lymphoma and pediatric osteosarcoma.
Despite its wide range of therapeutic efficacy, the toxicities of HD-MTX including reversible
myelosuppression, nausea, vomiting, diarrhea, hepatotoxicity, nephrotoxicity, neurotoxicity,
and particularly oral mucositis should not be neglected. Accumulating pharmacogenetic studies
have revealed that polymorphisms of enzymes involved in folate pathway could lead to
variability in response to MTX and HD-MTX-related toxicities in various malignancies. The
most two extensively studied SNPs of MTHFR in relation to the toxicities of MTX are the C677T
variant (Ala222Val, rs1801133) and A1298C variant (Glu 429Ala, rs1801131), both dampening the
enzyme activity by 40-70%.
However, limited evidence is available in pediatric NHL, with results varying considerably in
different studies. Therefore, the aim of this retrospective study was to evaluate the
influence of C677T and A1298C polymorphisms on HD-MTX-related toxicities in children with NHL
treated according to BFM-modified protocols.
PATIENTS & METHODS：We reviewed the medical records of all pediatric patients who were
diagnosed as NHL and received HD-MTX-based chemotherapy at the dose of 5g/m2 in Sun Yat-sen
University Cancer Center between March 2014 and March 2019. Data were analyzed by chi-square
test.
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