Low-intensity therapy cures over 40 % of children with rapid Flow-MRD responding ALL: the ALL-MB 2008 trial results

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Abstract

   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.

About the authors

A. Popov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: uralcytometry@gmail.com
ORCID iD: 0000-0002-0889-6986

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

ory Mashela St., Moscow 117997

Россия

G. Henze

Charité – Universitätsmedizin Berlin

Department of Pediatric Oncology Hematology

Berlin

Германия

Yu. Roumiantseva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-9670-3728

Moscow

Россия

O. Budanov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

ORCID iD: 0000-0003-3232-2322

Moscow, Russian Federation

Borovlyany, Minsk District, Belarus

Россия

M. Belevtsev

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Borovlyany, Minsk District

Белоруссия

T. Verzhbitskaya

Regional Children’s Hospital; Research Institute of Medical Cell Technologies

ORCID iD: 0000-0001-9329-1828

Ekaterinburg

Россия

E. Boyakova

Moscow City Blood Center named after O. K. Gavrilov

Moscow

Россия

L. Movchan

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Borovlyany, Minsk District, Belarus

Белоруссия

G. Tsaur

Regional Children’s Hospital; Research Institute of Medical Cell Technologies

ORCID iD: 0000-0002-9881-6221

Ekaterinburg

Россия

M. Fadeeva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Moscow

Россия

S. Lagoyko

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-3793-104X

Moscow

Россия

L. Zharikova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-1105-8676

Moscow

Россия

N. Myakova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-4779-1896

Moscow

Россия

D. Litvinov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-7461-0050

Moscow

Россия

O. Khlebnikova

Regional Children’s Hospital; Research Institute of Medical Cell Technologies

Ekaterinburg

Россия

O. Streneva

Regional Children’s Hospital; Research Institute of Medical Cell Technologies

Ekaterinburg

Россия

E. Stolyarova

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Borovlyany, Minsk District

Белоруссия

N. Ponomareva

Republican Children’s Hospital

ORCID iD: 0000-0002-6499-0977

Moscow

Россия

G. Novichkova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2322-5734

Moscow

Россия

L. Fechina

Regional Children’s Hospital; Research Institute of Medical Cell Technologies

ORCID iD: 0000-0002-1885-3912

Ekaterinburg

Россия

O. Aleinikova

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Borovlyany, Minsk District

Белоруссия

A. Karachunskiy

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Moscow

Россия

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