Cancer chemotherapy and pharmacology · 2025
DNA-incorporated thioguanine to detect potential non-adherence to maintenance therapy in acute lymphoblastic leukemia.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Koch Mathilde Rønne, Buhl Rasmussen Anna Sofie, Als-Nielsen Bodil, Duarte Ximo, Escherich Gabriele, Heyman Mats, Lepik Kristi, Malmros Johan, Nersting Jacob, Johannsdottir Inga, Niinimäki Riitta, Petersen Malene Johanne, Segers Heidi, van der Sluis Inge Margriet, Thastrup Maria, Vaitkeviciene Goda, Schmiegelow Kjeld, Toksvang Linea Natalie
Аннотация
PURPOSE: Adherence to 6-mercaptopurine (6-MP)/methotrexate maintenance treatment for acute lymphoblastic leukemia (ALL) is pivotal to preventing relapse, and the 6-MP metabolite DNA-incorporated thioguanine (DNA-TG) is associated with relapse risk. In the ALLTogether-1 (A2G1) Maintenance sub-study (EU CT nr 2022-501050-11-01), DNA-TG, thioguanine nucleotides (TGN), and methylated mercaptopurine metabolites (MeMP) are analyzed regularly. Upon levels below preset limits (TGN < 50, or MeMP < 200 or < 100 nmol/mmol hemoglobin for thiopurine S-methyltransferase (TPMT) wild type and heterozygous patients, respectively), the treating physician is informed of potential non-adherence. We investigated the feasibility of using DNA-TG as the primary flagging of potential non-adherence.
METHODS: We analyzed 6-MP metabolites in 3,074 blood samples from 368 children enrolled in the A2G1 Maintenance sub-study.
RESULTS: In 6% of samples, TGN (median 212, 95% range 40-642), MeMP (median 4,959, 95% range 135-23,880) or both were below the flagging potential non-adherence limits. DNA-TG was associated with TGN (estimate = 1.72, p < 0.0001), MeMP (estimate = 1.10, p < 0.0001), and prescribed 6-MP dose (estimate = 1.083 and 1.132, p < 0.0001, for TPMT wild type and heterozygous patients) in linear effects models, and the predicted probability of treatment interruption in logistic regression models. DNA-TG was below 200 fmol TG/µg DNA (13th percentile of all measurements, median 569, 95% range 73-1,823) in all samples with both TGN and MeMP below the flagging potential non-adherence limits.
CONCLUSION: DNA-TG can provide a cost-effective guidance on when to measure TGN and MeMP to determine whether non-adherence should be suspected, which is an additional benefit to monitoring DNA-TG during maintenance therapy.
METHODS: We analyzed 6-MP metabolites in 3,074 blood samples from 368 children enrolled in the A2G1 Maintenance sub-study.
RESULTS: In 6% of samples, TGN (median 212, 95% range 40-642), MeMP (median 4,959, 95% range 135-23,880) or both were below the flagging potential non-adherence limits. DNA-TG was associated with TGN (estimate = 1.72, p < 0.0001), MeMP (estimate = 1.10, p < 0.0001), and prescribed 6-MP dose (estimate = 1.083 and 1.132, p < 0.0001, for TPMT wild type and heterozygous patients) in linear effects models, and the predicted probability of treatment interruption in logistic regression models. DNA-TG was below 200 fmol TG/µg DNA (13th percentile of all measurements, median 569, 95% range 73-1,823) in all samples with both TGN and MeMP below the flagging potential non-adherence limits.
CONCLUSION: DNA-TG can provide a cost-effective guidance on when to measure TGN and MeMP to determine whether non-adherence should be suspected, which is an additional benefit to monitoring DNA-TG during maintenance therapy.