Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children34310.24287/1726-1708-2020-19-2-93-102ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИThe effect of the minimum residual disease on the risk of relapse at allogeneic hematopoietic stem cell transplantation in children, adolescents, and young adults with acute lymphoblastic leukemiaВлияние значения минимальной остаточной болезни на риск развития рецидива при аллогенной трансплантации гемопоэтических стволовых клеток у детей, подростков и молодых пациентов с острым лимфобластным лейкозомhttps://orcid.org/0000-0002-7899-3773PrudnikovD. V.ПрудниковД. В.
Belarus

Hematologist Department of transplantation,

Republic of Belarus, 223053, Minsk region, Borovlyani v., Frunzenskaya st., 43

врач-гематолог отделения трансплантации,

Республика Беларусь, 223053, Минский район, д. Боровляны, ул. Фрунзенская, 43

dima1911@mail.ruhttps://orcid.org/0000-0003-4172-9466MareikoYu. E.МарейкоЮ. Е.
Belarus
https://orcid.org/0000-0002-3193-4864KirsanovaN. P.КирсановаН. П.
Belarus
https://orcid.org/0000-0003-4814-804XMinakovskayaN. V.МинаковскаяН. В.
Belarus
https://orcid.org/0000-0003-0143-1921AleinikovaO. V.АлейниковаО. В.
Belarus
Belarusian research center for pediatric oncology, hematology and immunologyГУ «Республиканский научно-практический центр детской онкологии, гематологии и иммунологии»02072020192931020107202001072020Copyright ©; 2020, «D. Rogachev NMRCPHOI»Copyright ©; 2020, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2020«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/343

Minimal residual disease (MRD) is an independent predictor of relapse risk for childhood acute lymphoblastic leukemia(ALL). The aim of study to investigate impact MRD by real-time quantitative polymerase chain reaction before (day –21) andat +30 ± 10, +60 ± 10, +100 ± 10, +180 ± 10, +365 ± 10 days after hematopoietic stem cell transplantation (HSCT), and PCR-chimerismon transplant outcomes children with ALL. The study was approved by the Independent Ethics Committee and the Scientific Councilof the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Republic of Belarus). Fifty one patientswith ALL underwent allogeneic transplantation in remission (period 12.2010–12.2017, median follow-up 2,8 years). 3-years eventfreesurvival (EFS) and cumulative incidence of relapse (CIR) were 71.6 ± 17.1% and 14.3 ± 14.3% respectively for patients (n = 7)with pre-transplant MRD < 10-4 and 0% (n = 4, p = 0.0046) and 50.0 ± 29.2% (p = 0.3111) respectively for MRD ≥ 10-4. After HSCT(n = 29) 3-years EFS and CIR were 22.2 ± 13.9% and 66.7 ± 18.1% respectively for recipients (n = 9) with MRD ≥ 10-4 at leastin one analyzed point. In comparison, patients with MRD < 10-4 at all points (n = 20) had EFS and CIR 70.0 ± 10.2% (p = 0.0172)(HR = 12.3; 95% CI: 2.33–64.87; p = 0.0031), and 5.0±5.0% (p = 0.0004) (HR = 50.7; 2.5–97.5% CI: 1.60–1608.56; p = 0.0260)respectively. Patients with mixed chimerism at least in one analyzed point since day +30 to +365 hadn't significant differences OS,EFS, CIR but were worse (57.1%, 40.0% and 50.0% respectively) in comparison full chimerism patients (79.5% (p = 0.248), 71.4%(p = 0.072) and 20.0% (p = 0.070) respectively). MRD is significant predictor of relapse risk for childhood ALL at time of HSCT.MRD < 10-4 patients have significantly better EFS and CIR in comparison MRD ≥ 10-4 patients before and after HSCT.

Минимальная остаточная болезнь (МОБ) – независимый фактор риска рецидива у детей сострым лимфобластным лейкозом (ОЛЛ). Цель работы: оценить влияние МОБ, отслеживаемой пореаранжировкам генов IgH, IgK, TCRB, TCRG, TCRD перед аллогенной трансплантацией гемопоэтическихстволовых клеток (алло-ТГСК) и после нее, химеризма, определенного методом полимеразнойцепной реакции (ПЦР), после ТГСК на частоту развития рецидива, общую (ОВ) и бессобытийную(БСВ) выживаемость у пациентов с ОЛЛ. Данное исследование одобрено независимым этическимкомитетом и утверждено решением ученого совета ГУ «Республиканский научно-практическийцентр детской онкологии, гематологии и иммунологии» (Республика Беларусь). С 2010 по2017 г. (медиана времени наблюдения после ТГСК – 2,8 года) 51 пациент с ОЛЛ в Центре детскойонкологии, гематологии и иммунологии Республики Беларусь получили алло-ТГСК. Медианавозраста пациентов составила 11,1 (2,6–32,8) года. Точками контроля перед и после ТГСК былиопределены следующие: день –21 перед ТГСК и дни +30 ± 10, +60 ± 10, +100 ± 10, +180 ± 10,+365 ± 10 после ТГСК. Перед ТГСК 3-летняя БСВ и кумулятивная частота рецидива (КЧР)составили 71,6 ± 17,1% и 14,3 ± 14,3% соответственно у пациентов (n = 7) со значениемМОБ < 10-4 и 0% (p = 0,0046) и 50,0 ± 29,2% (p = 0,3111) соответственно у больных (n = 4) при МОБ ≥ 10-4.После ТГСК (n = 29) 3-летняя БСВ и КЧР составили 22,2 ± 13,9% и 66,7 ± 18,1% соответственнодля реципиентов (n = 9) с МОБ ≥ 10-4 хотя бы в одной из анализируемых точек против 70,0 ± 10,2%(p = 0,0172) (отношение рисков (ОР) = 12,3; 95% доверительный интервал (ДИ): 2,33–64,87;p = 0,0031), и 5,0 ± 5,0% (p = 0,0004) (ОР = 50,7; 2,5–97,5% ДИ: 1,60–1608,56; p = 0,0260)соответственно для пациентов (n = 20) со значением МОБ < 10-4 во всех точках. Реципиентысо смешанным химеризмом хотя бы в одном из исследуемых образцов костного мозга с дня+30 по день +365 имели показатели ОВ (57,1%), БСВ (40,0%) и КЧР (50,0%) хуже в сравнениис пациентами, у которых на протяжении года после ТГСК был полный донорский химеризм(79,5% (p = 0,248), 71,4% (p = 0,072) и 20,0% (p = 0,070) соответственно), хотя статистическойзначимости получено не было. МОБ является значимым фактором риска развития рецидиваи фактором, оказывающим влияние на выживаемость пациентов с ОЛЛ после алло-ТГСК.Пациенты со значением МОБ < 10-4 на этапах перед и после алло-ТГСК имеют статистическизначимо лучшие показатели БСВ и КЧР в сравнении с теми больными, у которых значениеМОБ ≥ 10-4.

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