The effects of NUDT15 and TPMT variants on mercaptopurine treatment in Vietnamese pediatric acute lymphoblastic leukemia patients.

6-mercaptopurine (6-MP) plays a critical role in the treatment of pediatric acute lymphoblastic leukemia (ALL). NUDT15 and TPMT gene variants have been strongly associated with myelotoxicity caused by using 6-MP. Therefore, the purpose of this study is to investigate the frequency of NUDT15 and TPMT polymorphisms, as well as the impact of NUDT15 variants on the use of 6-MP to treat pediatric ALL in Vietnam. Sanger sequencing was applied to detect NUDT15 and TPMT gene variants in 70 pediatric ALL patients. Duration of drug interruption, level of neutropenia, and 6-MP tolerance dose were recorded. NUDT15 variants were detected from 23 out of 70 (32.9%) patients. Three well-known haplotype variants were identified as NUDT15 *2 (p.V18_V19insGV and p.R139C), *3 (p.R139C), and *6 (p.V18_V19insGV); besides, a novel NUDT15 p.R11Q was not previously reported. The NUDT15 wild-type, heterozygous variant, and homozygous variant genotypes were 67.1%, 30.1%, and 2.8%, respectively. Two TPMT heterozygous polymorphisms were TPMT*3C and *6, accounted for 2.8%. Patients with intermediate and low activity NUDT15 were given the median 6-MP tolerance dose of 55.2 and 37.2 versus 69.5 mg/m2/day of patients with NUDT15 normal activity (p = 0.0001). Patients with homozygous variant diplotype were drastically sensitive to 6-MP, with an average dose intensity of 49.6%, compared to 73.6% and 92.7% of those with heterozygous and wild-type diplotype, respectively (p = 0.0001). Our results suggest that 6-MP dose adjustment should be based on NUDT15 variants in pediatric Vietnamese ALL patients.

T-cell large granular lymphocytic leukemia in Vietnam: Using microscope-to-screen videoconferencing to improve diagnosis.

OBJECTIVES: Leukemia diagnosis in Vietnam is limited by a lack of hematopathology training and expert consultation as well as the cost of high-magnification digitization of hematology slides. Screen-sharing software allows international collaboration with experienced hematopathologists for improved diagnostic accuracy. METHODS: A hematopathology education and consultation program was proposed for Vietnam hospitals. By appointment, pathologists in Vietnam with access to a microscope camera, imaging software, and high-speed internet were invited to review slides and data with a volunteer board-certified hematopathologist in the United States using secure videoconferencing software. A single hospital in southern Vietnam assigned a pathologist proficient in English to access this service. All consultations from this site with clinicopathologic information were logged. After a 2-year period of online consultation, case slides for selected diagnoses were reviewed under the microscope in Vietnam to assess concordance. RESULTS: In total, 135 consultations were logged, 53 of which were for blood and bone marrow. T-cell large granular lymphocytic leukemia (T-LGLL) was 1 of the most frequent bone marrow consultation-related diagnoses; all diagnoses of this entity were confirmed by in-person microscopy (100% concordance). A records search and physician surveys found no prior documented diagnoses of T-LGLL made in Vietnam before this education and consultation program. CONCLUSIONS: Our virtual consultation model has improved patient care in Vietnam by providing correct diagnoses to inform best practices in treatment. As a result of our program, the first Vietnam diagnoses of T-LGLL were made and may help expand on the literature in this area. This model could provide cost-effective, real-time consultation and education services for pathologists in underserved communities.