Abstract
The purpose of this work was evaluation of prognostic significance of 11q23/KMT2A rearrangements in infants (aged under 365 days) with B-cell precursor acute lymphoblastic leukemia (ALL) enrolled in Russian-Belarus multicenter trial MLLBaby. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Research Institute of Medical Cell Technologies (Ekaterinburg). Various 11q23/KMT2A rearrangements were revealed in 100 (72%) of 139 patients. Event-free survival (EFS) in the intermediate risk group of MLL-Baby trial was 35.1% (standard error (SE) 6.9%), in the high risk group – 38.3% (SE 7.1%) (p = 0.941). The most unfavorable prognosis had infants with translocation t(9;11)/KMT2A-MLLT3: EFS 18.8% (SE 9.8%), cumulative incidence of relapse (CIR) 75.0% (SE 9.7%). Intermediate results were obtained in patients with translocations t(4;11)/KMT2A-AFF1 and t(11;19)/KMT2A-MLLT1: EFS 36.9% (SE 7,2%) and 32,7% (SE 10.4%), respectively; CIR 46.3% (SE 7.8%) and 50.9% (SE 12.3%). The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3% (SE 15.2%), CIR 0,0%. In the multivariate analysis unfavorable outcome of KMT2A-rearranged infant ALL was associated with initial CNS involvement (p = 0.020), initial white blood cell count higher than 300 × 109 /L (p = 0.028), more than 5% blast cells on day 15 in bone marrow (p = 0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p = 0.012).
Highlights
Intermediate results were obtained in patients with translocations t(4;11)/KMT2A-AFF1 and t(11;19)/KMT2A-MLLT1: Event-free survival (EFS) 36.9% (SE 7,2%) and 32,7% (SE 10.4%), respectively; cumulative incidence of relapse (CIR) 46.3% (SE 7.8%) and 50.9% (SE 12.3%)
The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3% (SE 15.2%), CIR 0,0%
In the multivariate analysis unfavorable outcome of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) was associated with initial CNS involvement (p = 0.020), initial white blood cell count higher than 300 × 109/L (p = 0.028), more than 5% blast cells on day 15 in bone marrow (p = 0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p = 0.012)
Summary
Поступила 25.01.2021 Принята к печати 02.02.2021 жизни с острым лимфобластным лейкозом. Целью данной работы была оценка прогностической роли перестроек 11q23/KMT2A у детей первого года жизни с острым лимфобластным лейкозом (ОЛЛ) из B-линейных предшественников, включенных в российско-белорусское мультицентровое исследование MLL-Baby. Острый лимфобластный лейкоз (ОЛЛ) у детей первого года жизни характеризуется высокой частотой встречаемости перестроек гена KMT2A (ранее известного как MLL), достигающей 75% случаев [1, 2]. При ОЛЛ у детей первого года жизни наиболее частой перестройкой 11q23/KMT2A является транслокация t(4;11)/KMT2A-AFF1, на долю которой приходится около половины KMT2A-позитивных случаев. Суммарно на долю 5 наиболее частых генов-партнеров KMT2A (AFF1, MLLT1, MLLT3, MLLT10, EPS15) приходится более 90% всех случаев KMT2A-позитивных ОЛЛ у детей первого года жизни [6]. Традиционно считалось, что наиболее неблагоприятной является транслокация t(4;11)/KMT2A-AFF1, в то время как прогноз для пациентов с транслокациями t(11;19)/MLL-MLLT1, t(9;11)/MLL-MLLT3 и другими (более редкими) перестройками 11q23/ KMT2A несколько лучше [3].
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