Prognostic significance of various 11q23/KMT2A rearrangements in infants with acute lymphoblastic leuekemia

G. A. Tsaur; Цаур Г. А.; T. O. Riger; Ригер Т. О.; A. M. Popov; Попов А. М.; A. M. Kustanovich; Кустанович А. М.; Yu. V. Olshanskaya; Ольшанская Ю. В.; T. V. Nasedkina; Наседкина Т. В.; A. G. Solodovnikov; Солодовников А. Г.; E. V. Shorikov; Шориков Е. В.; A. S. Demina; Демина А. С.; O. M. Plekhanova; Плеханова О. М.; E. S. Nokhrina; Нохрина Е. С.; T. Yu. Verzhbitskaya; Вержбицкая Т. Ю.; O. V. Streneva; Стренева О. В.; O. V. Makarova; Макарова О. В.; O. R. Arakaev; Аракаев О. Р.; L. I. Seveliev; Савельев Л. И.; O. V. Aleinikova; Алейникова О. В.; E. S. Lapotentova; Лапотентова Е. С.; N. V. Myakova; Мякова Н. В.; V. V. Fominykh; Фоминых В. В.; K. L. Kondratchik; Кондратчик К. Л.; E. G. Boichenko; Бойченко Е. Г.; N. I. Ponomareva; Пономарева Н. И.; A. I. Karachunskiy; Карачунский А. И.; A. G. Roumiantsev; Румянцев А. Г.; L. G. Fechina; Фечина Л. Г.

doi:10.24287/1726-1708-2021-20-1-27-39

Prognostic significance of various 11q23/KMT2A rearrangements in infants with acute lymphoblastic leuekemia

Authors: Tsaur G.A.¹^,2^,3, Riger T.O.¹^,2, Popov A.M.⁴, Kustanovich A.M.⁵, Olshanskaya Y.V.⁴, Nasedkina T.V.⁶, Solodovnikov A.G.²^,3, Shorikov E.V.⁷, Demina A.S.¹^,2, Plekhanova O.M.¹, Nokhrina E.S.¹, Verzhbitskaya T.Y.¹^,2, Streneva O.V.¹^,2, Makarova O.V.¹, Arakaev O.R.¹^,2, Seveliev L.I.¹^,2^,3, Aleinikova O.V.⁴^,8, Lapotentova E.S.⁷, Myakova N.V.⁴, Fominykh V.V.⁴, Kondratchik K.L.⁹, Boichenko E.G.¹⁰, Ponomareva N.I.¹¹, Karachunskiy A.I.⁴, Roumiantsev A.G.⁴, Fechina L.G.¹²
Affiliations:
1. Regional Children’s Hospital
2. Research Institute of Medical Cell Technologies
3. Ural State Medical University of Ministry of Healthcare of the Russian Federation
4. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
5. The Sharett Institute of Oncology, Hadassah Medical Center
6. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
7. PET-Technology Center of Nuclear Medicine
8. Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
9. Morozov Children's City Clinical Hospital of the Moscow City Healthcare Department
10. City Children’s Hospital №1
11. Russian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, of Ministry of Healthcare of the Russian Federation
12. Regional Children’s Hospital Research Institute of Medical Cell Technologies
Issue: Vol 20, No 1 (2021)
Pages: 27-39
Section: ORIGINAL ARTICLES
Submitted: 14.04.2021
Accepted: 14.04.2021
Published: 14.04.2021
URL: https://hemoncim.com/jour/article/view/477
DOI: https://doi.org/10.24287/1726-1708-2021-20-1-27-39
ID: 477

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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).

Keywords

acute lymphoblastic leukemia, prognosis, infants, 11q23/KMT2A rearrangements

About the authors

G. A. Tsaur

Regional Children’s Hospital;
Research Institute of Medical Cell Technologies;
Ural State Medical University of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: tsaur@mail.ru
ORCID iD: 0000-0002-9881-6221

Dr. Med. Sci., Head of the Laboratory of Molecular Biology, Immunophenotyping and Pathomorphology;
a leading researcher at the Laboratory of Cellular Therapy for Oncohematological Diseases;

Associate Professor at the Department of Clinical Laboratory Diagnostics and Bacteriology,

32 S. Deryabinoy St., Ekaterinburg 620149

Russian Federation

T. O. Riger

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

Ekaterinburg

Russian Federation

A. M. Popov

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

ORCID iD: 0000-0002-0889-6986

Moscow

Russian Federation

A. M. Kustanovich

The Sharett Institute of Oncology, Hadassah Medical Center

Jerusalem

Israel

Yu. V. Olshanskaya

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

ORCID iD: 0000-0002-2352-7716

Moscow

Russian Federation

T. V. Nasedkina

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Moscow

Russian Federation

A. G. Solodovnikov

Research Institute of Medical Cell Technologies;
Ural State Medical University of Ministry of Healthcare of the Russian Federation

Ekaterinburg

Russian Federation

E. V. Shorikov

PET-Technology Center of Nuclear Medicine

Ekaterinburg

Russian Federation

A. S. Demina

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

Ekaterinburg

Russian Federation

O. M. Plekhanova

Regional Children’s Hospital

Ekaterinburg

Russian Federation

E. S. Nokhrina

Regional Children’s Hospital

Ekaterinburg

Russian Federation

T. Yu. Verzhbitskaya

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

ORCID iD: 0000-0001-9329-1828

Ekaterinburg

Russian Federation

O. V. Streneva

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

Ekaterinburg

Russian Federation

O. V. Makarova

Regional Children’s Hospital

Ekaterinburg

Russian Federation

O. R. Arakaev

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

Ekaterinburg

Russian Federation

L. I. Seveliev

Regional Children’s Hospital;
Research Institute of Medical Cell Technologies;
Ural State Medical University of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-5180-6560

Ekaterinburg

Russian Federation

O. V. Aleinikova

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

ORCID iD: 0000-0003-0143-1921

Moscow;

Minsk

Belarus

E. S. Lapotentova

PET-Technology Center of Nuclear Medicine

Ekaterinburg

Belarus

N. V. 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

Russian Federation

V. V. Fominykh

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

Moscow

Russian Federation

K. L. Kondratchik

Morozov Children's City Clinical Hospital of the Moscow City Healthcare Department

Moscow

Russian Federation

E. G. Boichenko

City Children’s Hospital №1

Saint-Petersburg

Russian Federation

N. I. Ponomareva

Russian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, of Ministry of Healthcare of the Russian Federation

Moscow

Russian Federation