Frequency of Thiopurine S-methyltransferase (TPMT) Genotypes Among Patients With Acute Lymphoblastic Leukemia at a Tertiary Care Hospital in Bangladesh: A Cross-Sectional Study.
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BACKGROUND: 6-Mercaptopurine is central to consolidation and maintenance therapy in acute lymphoblastic leukemia (ALL). Thiopurine S-methyltransferase (TPMT) inactivates its cytotoxic thioguanine nucleotides, and loss-of-function TPMT variants predispose carriers to severe myelosuppression at conventional doses. Published Bangladeshi evidence is confined to children. This study determined the frequency and distribution of laboratory-reported TPMT diplotypes and the corresponding predicted metabolizer phenotypes among Bangladeshi patients with ALL. METHODS: This cross-sectional study was conducted in the Department of Hematology and Bone Marrow Transplantation Unit, Dhaka Medical College Hospital, Dhaka, from February 2023 to July 2024. All eligible, consenting patients with newly diagnosed ALL were enrolled consecutively, and 40 were analyzed. Genotyping was outsourced to two commercial laboratories, which sequenced complementary DNA reverse transcribed from peripheral blood RNA rather than the genomic DNA specified by international recommendations; the assay was therefore nonstandard and unvalidated, and haplotype phasing was not performed. Reported diplotypes were translated into predicted metabolizer phenotypes. Exact binomial 95% confidence intervals (CIs) were calculated, and association analyses were post hoc and exploratory, using two-sided exact tests. RESULTS: Among the participants, 31 (77.5%) were male patients, and 24 (60.0%) had B-lineage ALL. Thirty-eight carried TPMT*1/*1 and were predicted normal metabolizers (95.0%; exact 95% CI, 83.1-99.4), and two were predicted intermediate metabolizers (5.0%; 0.6-16.9), reported as TPMT*1/*3A and TPMT*1/*3C. No poor metabolizer was identified on the diplotypes as reported (0/40; 0.0-8.8). Because the phase was not established, the patient reported as TPMT*1/*3A could instead carry TPMT*3B and TPMT*3C in trans and would then be a poor metabolizer requiring an approximately 10-fold rather than twofold dose reduction, leaving one intermediate and one poor metabolizer. Exploratory tests detected no difference by sex, immunophenotypic subtype, or hematological parameters, but had no meaningful power. CONCLUSIONS: In this study, two of 40 Bangladeshi patients with ALL carried a reported reduced-function TPMT diplotype. Because every call derived from a nonstandard, unvalidated RNA-based assay and the TPMT*3A phase remains unresolved, these estimates are provisional and require DNA-based, phased confirmation. They nonetheless support international guidance favoring pretreatment TPMT genotyping. Combined NUDT15 testing is indicated by published Asian evidence rather than by these data, since NUDT15 was not assessed. Larger multicenter studies with prospective toxicity follow-up are needed.