Cancers (Sep 2023)
Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia—Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022
- Małgorzata Czogała,
- Wojciech Czogała,
- Katarzyna Pawińska-Wąsikowska,
- Teofila Książek,
- Karolina Bukowska-Strakova,
- Barbara Sikorska-Fic,
- Paweł Łaguna,
- Anna Fałkowska,
- Katarzyna Drabko,
- Katarzyna Muszyńska-Rosłan,
- Maryna Krawczuk-Rybak,
- Marta Kozłowska,
- Ninela Irga-Jaworska,
- Karolina Zielezińska,
- Tomasz Urasiński,
- Natalia Bartoszewicz,
- Jan Styczyński,
- Jolanta Skalska-Sadowska,
- Jacek Wachowiak,
- Anna Rodziewicz-Konarska,
- Krzysztof Kałwak,
- Małgorzata Ciebiera,
- Radosław Chaber,
- Agnieszka Mizia-Malarz,
- Agnieszka Chodała-Grzywacz,
- Grażyna Karolczyk,
- Katarzyna Bobeff,
- Wojciech Młynarski,
- Katarzyna Mycko,
- Wanda Badowska,
- Renata Tomaszewska,
- Tomasz Szczepański,
- Katarzyna Machnik,
- Natalia Zamorska,
- Walentyna Balwierz,
- Szymon Skoczeń
Affiliations
- Małgorzata Czogała
- Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Wojciech Czogała
- Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Katarzyna Pawińska-Wąsikowska
- Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Teofila Książek
- Department of Pediatric Oncology and Hematology, University Children Hospital, 30-683 Krakow, Poland
- Karolina Bukowska-Strakova
- Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Barbara Sikorska-Fic
- Department of Pediatrics, Oncology, Hematology and Transplantology, Medical University of Warsaw, 02-091 Warszawa, Poland
- Paweł Łaguna
- Department of Pediatrics, Oncology, Hematology and Transplantology, Medical University of Warsaw, 02-091 Warszawa, Poland
- Anna Fałkowska
- Department of Paediatric Haematology and Oncology and Transplantology, Medical University of Lublin, 20-095 Lublin, Poland
- Katarzyna Drabko
- Department of Paediatric Haematology and Oncology and Transplantology, Medical University of Lublin, 20-095 Lublin, Poland
- Katarzyna Muszyńska-Rosłan
- Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-089 Bialystok, Poland
- Maryna Krawczuk-Rybak
- Department of Pediatric Oncology and Hematology, Medical University of Bialystok, 15-089 Bialystok, Poland
- Marta Kozłowska
- Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 80-210 Gdansk, Poland
- Ninela Irga-Jaworska
- Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 80-210 Gdansk, Poland
- Karolina Zielezińska
- Department of Paediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
- Tomasz Urasiński
- Department of Paediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
- Natalia Bartoszewicz
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, 85-094 Bydgoszcz, Poland
- Jan Styczyński
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, 85-094 Bydgoszcz, Poland
- Jolanta Skalska-Sadowska
- Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 60-572 Poznan, Poland
- Jacek Wachowiak
- Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 60-572 Poznan, Poland
- Anna Rodziewicz-Konarska
- Department of Bone Marrow Transplantation, Pediatric Oncology and Hematology, Medical University of Wroclaw, 50-556 Wroclaw, Poland
- Krzysztof Kałwak
- Department of Bone Marrow Transplantation, Pediatric Oncology and Hematology, Medical University of Wroclaw, 50-556 Wroclaw, Poland
- Małgorzata Ciebiera
- Clinic of Pediatric Oncology and Hematology, State Hospital 2, 35-301 Rzeszów, Poland
- Radosław Chaber
- Clinic of Pediatric Oncology and Hematology, State Hospital 2, 35-301 Rzeszów, Poland
- Agnieszka Mizia-Malarz
- Department of Oncology, Hematology and Chemotherapy, Upper Silesia Children’s Care Health Centre, 40-752 Katowice, Poland
- Agnieszka Chodała-Grzywacz
- Department of Pediatric Hematology and Oncology, Regional Polyclinic Hospital in Kielce, 25-736 Kielce, Poland
- Grażyna Karolczyk
- Department of Pediatric Hematology and Oncology, Regional Polyclinic Hospital in Kielce, 25-736 Kielce, Poland
- Katarzyna Bobeff
- Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 91-738 Lodz, Poland
- Wojciech Młynarski
- Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 91-738 Lodz, Poland
- Katarzyna Mycko
- Department of Pediatrics and Hematology and Oncology, Province Children’s Hospital, 10-561 Olsztyn, Poland
- Wanda Badowska
- Department of Pediatrics and Hematology and Oncology, Province Children’s Hospital, 10-561 Olsztyn, Poland
- Renata Tomaszewska
- Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
- Tomasz Szczepański
- Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
- Katarzyna Machnik
- Department of Pediatrics, Hematology and Oncology, City Hospital, 41-500 Chorzow, Poland
- Natalia Zamorska
- Student Scientific Group of Pediatric Oncology and Hematology, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Walentyna Balwierz
- Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
- Szymon Skoczeń
- Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
- DOI
- https://doi.org/10.3390/cancers15184557
- Journal volume & issue
-
Vol. 15,
no. 18
p. 4557
Abstract
Background: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10–15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. Methods: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). Results: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). Conclusions: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.
Keywords