Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children62110.24287/1726-1708-2022-21-2-95-104ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИLow-intensity therapy cures over 40 % of children with rapid Flow-MRD responding ALL: the ALL-MB 2008 trial resultsLow-intensity therapy cures over 40 % of children with rapid Flow-MRD responding ALL: the ALL-MB 2008 trial resultshttps://orcid.org/0000-0002-0889-6986PopovA.
Russian Federation

Alexander M. Popov, MD, PhD, head of Leukemia immunophenotyping laboratory1 Sam

ory Mashela St., Moscow 117997

Alexander M. Popov, MD, PhD, head of Leukemia immunophenotyping laboratory

1 Samory Mashela St., Moscow 117997

uralcytometry@gmail.comHenzeG.
Germany

Department of Pediatric Oncology Hematology

Berlin

https://orcid.org/0000-0001-9670-3728RoumiantsevaYu.
Russian Federation

Moscow

https://orcid.org/0000-0003-3232-2322BudanovO.
Russian Federation

Moscow, Russian Federation

Borovlyany, Minsk District, Belarus

Moscow, Russian Federation

Borovlyany, Minsk District, Belarus

 

BelevtsevM.
Belarus

Borovlyany, Minsk District

https://orcid.org/0000-0001-9329-1828VerzhbitskayaT.
Russian Federation

Ekaterinburg

BoyakovaE.
Russian Federation

Moscow

MovchanL.
Belarus

Borovlyany, Minsk District, Belarus

Borovlyany, Minsk District

https://orcid.org/0000-0002-9881-6221TsaurG.
Russian Federation

Ekaterinburg

FadeevaM.
Russian Federation

Moscow

https://orcid.org/0000-0002-3793-104XLagoykoS.
Russian Federation

Moscow

https://orcid.org/0000-0002-1105-8676ZharikovaL.
Russian Federation

Moscow

https://orcid.org/0000-0002-4779-1896MyakovaN.
Russian Federation

Moscow

https://orcid.org/0000-0002-7461-0050LitvinovD.
Russian Federation

Moscow

KhlebnikovaO.
Russian Federation

Ekaterinburg

StrenevaO.
Russian Federation

Ekaterinburg

StolyarovaE.
Belarus

Borovlyany, Minsk District

https://orcid.org/0000-0002-6499-0977PonomarevaN.
Russian Federation

Moscow

https://orcid.org/0000-0002-2322-5734NovichkovaG.
Russian Federation

Moscow

https://orcid.org/0000-0002-1885-3912FechinaL.
Russian Federation

Ekaterinburg

AleinikovaO.
Belarus

Borovlyany, Minsk District

Minsk District

Borovlyany

KarachunskiyA.
Russian Federation

Moscow

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationCharité – Universitätsmedizin BerlinBelarusian Research Center for Pediatric Oncology, Hematology and ImmunologyRegional Children’s HospitalResearch Institute of Medical Cell TechnologiesMoscow City Blood Center named after O. K. GavrilovRepublican Children’s Hospital08072022212951042406202224062022Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/621

   Serious side effects occur during therapy for childhood acute lymphoblastic leukemia (ALL), and survivors can experience long-term consequences. This study aimed at identifying patients who can be successfully treated with low treatment intensity combining clinical parameters and minimal residual disease (MRD) measurements. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. ALL-MB studies used reduced-intensity therapy from the beginning, for standard risk (SR) patients no cyclophosphamide, a very low daunorubicin dose, no high dose of methotrexate, no cranial irradiation. In the ALL-MB 2008 study, 1702 children (49.1 % of all patients) were classified as SR due to favorable initial characteristics. These included 295 patients treated in institutions who took part in a pilot study on MRD measurement using flow cytometry on day 15 and/or at the end of induction (EOI). The most suitable time point for MRD measurement was EOI with threshold 0.1% in 90.5 % of the patients with excellent results: event-free survival of 95 % and overall survival of 97 %, that identified the large proportion of patients (more than 40 % of all ALL patients). The outcome of children with slower MRD response was significantly worse. Initial SR characteristics plus one single MRD measurement at EOI identify more than 40 % of all children with ALL who can be successfully treated with low-intensity regimens as used in the MB protocols.

   Serious side effects occur during therapy for childhood acute lymphoblastic leukemia (ALL), and survivors can experience long-term consequences. This study aimed at identifying patients who can be successfully treated with low treatment intensity combining clinical parameters and minimal residual disease (MRD) measurements. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. ALL-MB studies used reduced-intensity therapy from the beginning, for standard risk (SR) patients no cyclophosphamide, a very low daunorubicin dose, no high dose of methotrexate, no cranial irradiation. In the ALL-MB 2008 study, 1702 children (49.1 % of all patients) were classified as SR due to favorable initial characteristics. These included 295 patients treated in institutions who took part in a pilot study on MRD measurement using flow cytometry on day 15 and/or at the end of induction (EOI). The most suitable time point for MRD measurement was EOI with threshold 0.1% in 90.5 % of the patients with excellent results: event-free survival of 95 % and overall survival of 97 %, that identified the large proportion of patients (more than 40 % of all ALL patients). The outcome of children with slower MRD response was significantly worse. Initial SR characteristics plus one single MRD measurement at EOI identify more than 40 % of all children with ALL who can be successfully treated with low-intensity regimens as used in the MB protocols.

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