Study on Relationships of Tumor Status and Gene Polymorphism With Blood Concentration of MTX and Toxicities in 63 Pediatric Mature B Cell Lymphoma in Chinese Population.

Abstract

OBJECTIVE:

This study investigated the relationships of tumor status (stage, renal involvement, bone marrow status, bulky disease, liver function), tumor gene polymorphism, and methotrexate (MTX) dosage (stratified by treatment group) with blood MTX levels and adverse reactions (ADR).

METHODS:

We retrospectively reviewed 63 mature B cell lymphoma patients who were treated in our center. Genotyping of the MTHFR 677 and SLCO1B1 genes was carried out, and the relationships between tumor status, polymorphism of the genes, MTX level, and ADR were analyzed.

RESULTS:

Altogether, 63 children were included. The mean blood MTX concentration was 0.25 ± 0.2 umol/L at 45 h. Liver dysfunction and bulky disease were both correlated with MTX level (both P < 0.05). ADRs were higher among patients with blood MTX > 0.5 mmol/l at 45 h than for the groups with lower blood MTX. The MTHFR 677 CT genotype was correlated with liver function damage (P = 0.04); the rs11045879 locus CC genotype of SLCO1B1, stage IV, and bulky disease at the time of diagnosis were correlated with 4° neutropenia (P < 0.05). Stage IV, bulky disease, leukemia stage at the time of diagnosis, and C2 treatment group were correlated with severe anemia (P < 0.05). Stage IV, bulky disease, leukemia stage, renal invasion at the time of diagnosis, and C2 treatment group were associated with severe thrombocytopenia (P < 0.05). Bulky disease and renal invasion at the time of diagnosis were associated with severe mucositis and severe infection (P < 0.05).

CONCLUSION:

Taken together, our data demonstrate that gene polymorphism, MTX levels, tumor status, and treatment group might be useful to optimize MTX therapy and estimate toxicity.

• Authors: Shuang Huang, Lin Jin, Jing Yang, Long Yan Duan, Meng Zhang, Ju Chun Zhou, Hong Yong Zhang
• Journal: Technology in cancer research & treatment (Technol Cancer Res Treat) 2021 Jan-Dec Vol. 20 Pg. 1533033821995288 ISSN: 1533-0338 [Electronic] United States
• PMID: 33752528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Liver-Specific Organic Anion Transporter 1
• SLCO1B1 protein, human
• MTHFR protein, human
• Methylenetetrahydrofolate Reductase (NADPH2)
• Methotrexate

Topics

• Adolescent
• Anemia (chemically induced)
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, blood)
• Bone Marrow (pathology)
• Chemical and Drug Induced Liver Injury (genetics)
• Child
• Child, Preschool
• China
• Female
• Genotype
• Humans
• Infant
• Liver (physiopathology)
• Liver-Specific Organic Anion Transporter 1 (genetics)
• Lymphoma, B-Cell (blood, drug therapy, pathology)
• Male
• Methotrexate (administration & dosage, adverse effects, blood)
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Neoplasm Staging
• Neutropenia (chemically induced, genetics)
• Polymorphism, Single Nucleotide
• Retrospective Studies
• Stomatitis (chemically induced)
• Thrombocytopenia (chemically induced)