Abstract
191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction. Minimal residual disease (MRD) was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001): 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS) of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 %) belonged to group with poor outcome (EFS 56.7 ± 9.0 %). At the end of remission induction (day 36) 36 children (18.85 %) with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001). From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.
Highlights
Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity
191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study
Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction
Summary
Прогностическое значение МОБ, определенной после окончания индукционной терапии Пациенты, у которых МОБ выявлялась на 85-й день терапии и после HR1, имели крайне неблагоприятный прогноз по сравнению с остальными детьми (БСВ 34,6 ± 13,3 и 89,8 ± 2,4 % соответственно; p < 0,0001). Результаты определения МОБ в данной точке наблюдения позволили выявить пациентов с худшим прогнозом и среди тех, у кого на 36-й день выявлялось более 0,1 % опухолевых клеток (БСВ 66,7 ± 10,3 и 28,6 ± 13,3 % соответственно), однако различия статистической значимости не достигли (p = 0,1225). Все неблагоприятные события (n = 9) произошли среди пациентов, остававшихся МОБ-позитивными (не ниже 0,001 %) и при дальнейшем наблюдении (n = 11), но не среди тех, кто в данной точке наблюдения последний раз был МОБ-позитивным (n = 5). БСВ в этих группах составила 18,2 ± 10,3 и 100 % соответственно (р = 0,0254). БСВ в различных группах пациентов в зависимости от результатов определения МОБ на 15-й день терапии
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