Genetic characteristics and treatment outcome in infants with KMT2A germline B-cell precursor acute lymphoblastic leukemia: Results of MLL-Baby protocol
Corresponding Author
Alexander Popov
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Correspondence
Alexander M. Popov, National Research Centre of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St, Moscow 117998, Russian Federation.
Email: [email protected]
Search for more papers by this authorGrigory Tsaur
Regional Children's Hospital, Ekaterinburg, Russian Federation
Ural State Medical University, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorZhan Permikin
Regional Children's Hospital, Ekaterinburg, Russian Federation
Ural State Medical University, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorGuenter Henze
Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorTatiana Verzhbitskaya
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Plekhanova
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorEkaterina Nokhrina
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorAlena Valochnik
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorPetr Sibiryakov
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorElena Zerkalenkova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorYulia Olshanskaya
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorTatiana Gindina
R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University of Saint Petersburg, Saint Petersburg, Russian Federation
Search for more papers by this authorLiudmila Movchan
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorEgor Shorikov
PET-Technology Centre of Nuclear Medicine, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Streneva
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Khlebnikova
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Makarova
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorOleg Arakaev
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorElmira Boichenko
City Children's Hospital No. 1, Saint Petersburg, Russian Federation
Search for more papers by this authorKonstantin Kondratchik
Morozov Children's Hospital, Moscow, Russian Federation
Search for more papers by this authorNatalia Ponomareva
Republican Children's Hospital, Moscow, Russian Federation
Search for more papers by this authorElena Lapotentova
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorOlga Aleinikova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorNatalia Miakova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorGalina Novichkova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorAlexander Karachunskiy
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorLarisa Fechina
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorCorresponding Author
Alexander Popov
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Correspondence
Alexander M. Popov, National Research Centre of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St, Moscow 117998, Russian Federation.
Email: [email protected]
Search for more papers by this authorGrigory Tsaur
Regional Children's Hospital, Ekaterinburg, Russian Federation
Ural State Medical University, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorZhan Permikin
Regional Children's Hospital, Ekaterinburg, Russian Federation
Ural State Medical University, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorGuenter Henze
Department of Pediatric Oncology Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorTatiana Verzhbitskaya
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Plekhanova
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorEkaterina Nokhrina
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorAlena Valochnik
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorPetr Sibiryakov
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorElena Zerkalenkova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorYulia Olshanskaya
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorTatiana Gindina
R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University of Saint Petersburg, Saint Petersburg, Russian Federation
Search for more papers by this authorLiudmila Movchan
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorEgor Shorikov
PET-Technology Centre of Nuclear Medicine, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Streneva
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Khlebnikova
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorOlga Makarova
Regional Children's Hospital, Ekaterinburg, Russian Federation
Search for more papers by this authorOleg Arakaev
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorElmira Boichenko
City Children's Hospital No. 1, Saint Petersburg, Russian Federation
Search for more papers by this authorKonstantin Kondratchik
Morozov Children's Hospital, Moscow, Russian Federation
Search for more papers by this authorNatalia Ponomareva
Republican Children's Hospital, Moscow, Russian Federation
Search for more papers by this authorElena Lapotentova
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorOlga Aleinikova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Belarussian Research Centre for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
Search for more papers by this authorNatalia Miakova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorGalina Novichkova
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorAlexander Karachunskiy
National Research and Clinical Centre for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Search for more papers by this authorLarisa Fechina
Regional Children's Hospital, Ekaterinburg, Russian Federation
Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation
Search for more papers by this authorAlexander Popov, Grigory Tsaur, and Larisa Fechina contributed equally to this work.
Abstract
The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
Supporting Information
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