Publikasi Scopus FKUI 2021 per tanggal 31 Agustus 2021 (582 artikel)

Rosdiana D.S., Setiabudy R., Andalusia R., Gatot D., Louisa M., Bardosono S., Instiaty I.
56955579800;6602316235;57191278723;6508292159;41461551400;21933841000;55703138400;
Tpmt genetic variability and its association with hematotoxicity in indonesian children with acute lymphoblastic leukemia in maintenance therapy
2021
Pharmacogenomics and Personalized Medicine
14
199
210
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Dharmais National Cancer Hospital, Jakarta, Indonesia; Drug Registration Directorate, National Agency for Drug and Food Control, Jakarta, Indonesia; Division of Hematology-Oncology, Department of Pediatrics, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Department of Nutrition, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
Rosdiana, D.S., Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Setiabudy, R., Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Andalusia, R., Dharmais National Cancer Hospital, Jakarta, Indonesia, Drug Registration Directorate, National Agency for Drug and Food Control, Jakarta, Indonesia; Gatot, D., Division of Hematology-Oncology, Department of Pediatrics, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Louisa, M., Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Bardosono, S., Department of Nutrition, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Instiaty, I., Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Purpose: Hematotoxicity monitoring in children with acute lymphoblastic leukemia (ALL) is critical to preventing life-threatening infections and drug discontinuation. The primary drug that causes hematotoxicity in ALL children is 6-mercaptopurine (6-MP). Genetic variability of the drug-metabolizing enzymes of 6-MP, thiopurine S-methyltransferase (TPMT), is one factor that might increase the susceptibility of children to hematotoxicity. The present study aimed to determine the variability in TPMT genotypes and phenotypes and its association with the occurrence of hematotoxicity in ALL children in maintenance therapy. Patients and Methods: A cross-sectional study was conducted at Cipto Mangunkusumo and Dharmais National Cancer Hospital, Jakarta, Indonesia, from June 2017 to October 2018. We included ALL patients, 1–18 years, who were receiving at least one month of 6-MP during maintenance therapy according to the Indonesian protocol for ALL 2013. Direct sequencing was used to determine TPMT*3A, *3B, and *3C genotypes, and LCMS/MS analysis was performed to measure the plasma concentrations of 6-MP and its metabolites. Association analysis between the TPMT genotype and hematotoxicity was evaluated using the unpaired t-test or Mann–Whitney’s test. Results: The prevalence of neutropenia, anemia, and thrombocytopenia in ALL children during maintenance therapy was 51.9%, 44.3%, and 6.6%, respectively. We found a low frequency of TPMT*3C, which is 0.95%. No association was found between hematotoxicity and TPMT genotypes or age, nutritional status, serum albumin levels, risk stratification, the daily dose of 6-MP, and cotrimoxazole co-administration. However, hematotoxicity was associated with 6-methylmercaptopurine (6-MeMP) plasma concentrations and the ratio 6-MeMP/6-thioguanine (6-TGN). We also found no association between TPMT genotypes and TPMT phenotypes. Conclusion: The 6-MeMP/6-TGN ratio is associated with hematotoxicity in ALL children during maintenance therapy but is not strong enough to predict hematotoxicity. © 2021 Rosdiana et al.
Mercaptopurine; Methylmercaptopurine; Neutropenia; Thioguanine; Thiopurine methyltransferase
6 methylthioinosine; albumin; cotrimoxazole; dexamethasone; methotrexate; thiopurine methyltransferase; tioguanine; vincristine; acute lymphoblastic leukemia; adolescent; adult; albumin blood level; anemia; Article; blood toxicity; child; cross-sectional study; drug blood level; drug safety; female; gene sequence; genetic variability; groups by age; human; human cell; Indonesia; Indonesian; liquid chromatography-mass spectrometry; maintenance therapy; major clinical study; male; neutropenia; nutritional status; prevalence; risk factor; thrombocytopenia; TPMT gene
Dove Medical Press Ltd
11787066
Article
Q2
845
5609