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High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia.

ABSTRACT: Sixty-three children (1-14 years of age) newly diagnosed with T-cell acute lymphoblastic leukemia were treated from January 2001 to December 2014. Patient outcomes were evaluated based on the regimen received; Capizzi methotrexate (C-MTX) vs. high-dose methotrexate (HDMTX). Complete remission (CR) was achieved in 54 of 60 (90.0%) patients and 3 patients died during induction. The 5-year overall survival (OS) and disease-free survival (DFS) were 88.3?±?6.5% and 85?±?7.5%, respectively. Post-induction, 35 patients were treated with HDMTX and 25 with C-MTX. There was no difference in OS or DFS for patients treated with HDMTX vs. C-MTX (P?>?0.05 for both). Central nervous system involvement (CNS3) was associated with inferior survival outcomes compared to Non-CNS3 patients (OS, CNS3 73.3?±?9.1% vs.non-CNS3 93.2?±?2.6%, (P?=?0.045) and DFS, CNS3 66.7?±?10.4% vs. non-CNS3 90.9?±?3.1% (P?=?0.0163)). Delayed radiation in CNS3 was associated with relapse (P?=?0.0037) regardless of regimen. Thus optimization of CNS-directed therapy for patients with CNS3 is needed.

SUBMITTER: Jastaniah W

PROVIDER: S-EPMC6215054 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia.

Jastaniah Wasil W Elimam Naglla N Abdalla Khalid K AlAzmi Aeshah A AA Aseeri Mohammed M Felimban Sami S

Leukemia research reports 20181009

Sixty-three children (1-14 years of age) newly diagnosed with T-cell acute lymphoblastic leukemia were treated from January 2001 to December 2014. Patient outcomes were evaluated based on the regimen received; Capizzi methotrexate (C-MTX) vs. high-dose methotrexate (HDMTX). Complete remission (CR) was achieved in 54 of 60 (90.0%) patients and 3 patients died during induction. The 5-year overall survival (OS) and disease-free survival (DFS) were 88.3 ± 6.5% and 85 ± 7.5%, respectively. Post-induc ...[more]

PMID: 30416957

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Project description:ObjectivesIt is well known that transporter and enzyme genes could be regulated by microRNA (miRNA) at the post-transcriptional level, and single-nucleotide polymorphisms (SNPs) in miRNA, which are involved in the miRNA production and structure, may impact the miRNA expression level and then influence drug transport and metabolism. In this study, we aim to evaluate the association between miRNA polymorphisms and high-dose methotrexate (HD-MTX) hematological toxicities in Chinese pediatric patients with acute lymphoblastic leukemia (ALL).MethodA total of 181 children with ALL were administered with 654 evaluable cycles of HD-MTX. Their hematological toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5. The association between 15 candidate SNPs of miRNA and hematological toxicities (leukopenia, anemia, and thrombocytopenia) was analyzed using Fisher's exact test. Further multiple backward logistic regression analysis was used to explore the independent risk factors for grade 3/4 hematological toxicities.ResultRs2114358 G>A in pre-hsa-miR-1206 was related to HD-MTX-related grade 3/4 leukopenia after multiple logistic regression [GA + AA vs. GG: odds ratio (OR): 2.308, 95% CI: 1.219-4.372, P = 0.010], and rs56103835 T > C in pre-hsa-mir-323b was associated with HD-MTX-related grade 3/4 anemia (TT + TC vs. CC: OR: 0.360, 95% CI: 0.239-0.541, P = 0.000); none of the SNPs were significantly associated with grade 3/4 thrombocytopenia. Bioinformatics tools predicted that rs2114358 G>A and rs56103835 T>C would impact the secondary structure of pre-miR-1206 and pre-miR-323b, respectively, and then probably influence the expression level of mature miRNAs and their target genes.ConclusionRs2114358 G>A and rs56103835 T>C polymorphism may potentially influence HD-MTX-related hematological toxicities, which may serve as candidate clinical biomarkers to predict grade 3/4 hematological toxicities in pediatric patients with ALL.

Dataset Information

High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia.

Publications

High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia.

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