Prognostic significance of IKZF1 deletions and IKZF1 plus profile in children with B-cell precursor acute lymphoblastic leukemia treated according to the ALL-IC BFM 2009 protocol.

Autor: Braun M; Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland.; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Pastorczak A; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Sędek Ł; Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland., Taha J; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Madzio J; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Jatczak-Pawlik I; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Wypyszczak K; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Matysiak M; Department of Pediatric Hematology and Oncology, Medical University of Warsaw, Warszawa, Poland., Derwich K; Department of Pediatric Hematology, Oncology and Transplantology, University of Medical Sciences, Poznan, Poland., Lejman M; Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland., Kazanowska B; Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Wroclaw, Wroclaw, Poland., Szczepański T; Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland., Kowalczyk JR; Department of Pediatric Hematology and Oncology, Medical University of Lublin, Lublin, Poland., Mlynarski W; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland.
Jazyk: angličtina
Zdroj: Hematological oncology [Hematol Oncol] 2022 Aug; Vol. 40 (3), pp. 430-441. Date of Electronic Publication: 2022 Feb 14.
DOI: 10.1002/hon.2973
Abstrakt: The strongest predictors of outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are minimal residual disease (MRD) and specific molecular abnormalities. One unfavorable prognostic factor is the presence of IKZF1 gene aberrations, particularly when co-occurring with high MRD level at the end of induction treatment. The present study determines the predictive value of a recently-defined IKZF1-plus (IKZF1 plus ) microdeletion profile in 373 children with BCP-ALL treated according to the ALL-intercontinental Berlin-Frankfurt-Munster protocol 2009 protocol. IKZF1-wild type (IKZF1 wt ) patients demonstrated lower leukemic burden parameters than those carrying IKZF1 deletion (IKZF1 del [n = 26, 7.0%]) or IKZF1 plus pattern (n = 34, 9.1%): (i) median blast percentage at diagnosis (78.0% vs. 86.9% vs. 86.0%; p = 0.021); (ii) median MRD level at day 15 of induction protocol (0.3% vs. 2.1% vs. 0.8%; p = 0.011); (iii) poor steroid response (7.6% vs. 26.5% vs. 12.5%; p = 0.010). Minimal residual disease level at day 33 (MRD33) exceeding 10 -4 was more frequently observed in both the IKZF1 del and IKZF1 plus subgroups than in IKZF1 wt patients (n = 9 [36.0%] vs. n = 13 [41.9%] vs. n = 70 [24.0%], p = 0.051). IKZF1 plus individuals showed a tendency for a lower MRD reduction between day 15 and 33 compared to IKZF1 del patients (p = 0.124). IKZF1 del and IKZF1 plus patients showed decreased relapse-free survival (HR [95%CI] for IKZF1 wt as reference = 2.72 [1.21-6.11] and 2.00 [0.87-4.49], respectively, p = 0.023). Both genetic markers including IKZF1 del and IKZF1 plus microdeletion profile provide additional predictive value of treatment outcome in childhood BCP-ALL and may contribute to more efficient patient stratification; the same is true in MRD guided protocols, which are based on flow cytometric measurements on day 15 of induction protocol.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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