Analysis of cytogenetic characteristics of primary childhood B-cell acute lymphoblastic leukemia and risk factors for first treatment response / 白血病·淋巴瘤

ABSTRACT

Objective:To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected, and the clinical characteristics, cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained. Genotyping, clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification (2018 version). The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed, and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results:The median age of 49 children was 3.0 years old (interquartile range 3.2 years old), 32 cases (65.3%) were male and 17 cases (34.7%) were female, with a male-to-female ratio of 1.88∶1. Thirty-five cases (71.4%) had gene mutations before treatment and 14 cases (28.6%) had no mutations. Among the 35 cases with mutations, E2A-PBX1 was found in 5 cases (10.2%), including 1 case with Philadelphia chromosome (Ph)-like; IKZF1 deletion was found in 8 cases (16.3%), including 4 cases with Ph-like, 1 case with Ph-positive, and 1 case with MLL rearrangement; MLL rearrangement was found in 3 cases (6.1%); Ph-like alone was found in 12 cases (24.5%); TEL-AML1 was found in 6 cases (12.2%), including 2 cases with Ph-like; 1 case (2.0%) with Ph-positive alone. The clinical risk stratification showed that 7 cases (14.3%) had high risk, 28 cases (57.1%) had intermediate risk, and 14 cases (28.6%) had low risk. The proportions of patients with high and intermediate clinical risk before induction chemotherapy [20.0% (7/35) vs. 0.0% (0/14), 62.9% (22/35) vs. 42.9% (6/14)] and the proportion of patients with altered mutation status on day 33 of induction chemotherapy [42.9% (15/35) vs. 0.0% (0/14)] were higher in patients with mutations before induction chemotherapy than those in patients without gene mutations before treatment (all P < 0.01). The gene mutation or not before treatment was not correlated with gender, white blood cell count at first diagnosis, hormone sensitivity, minimal residual disease (MRD) from the 15th to the 19th day of induction chemotherapy, and MRD on the 33rd day of induction chemotherapy (all P > 0.05). Clinical risk stratification of children was associated with white blood cell count at first diagnosis ( r = 0.392, P = 0.005), neutrophil count ( r = 0.453, P = 0.001), lymphocyte count ( r = 0.418, P = 0.001), monocyte count ( r = 0.359, P = 0.017), blood uric acid level ( r = 0.378, P = 0.007), and proportion of bone marrow naive lymphocyte count before treatment ( r = 0.316, P = 0.027) and from 15th to the 19th day of induction chemotherapy ( r = 0.399, P = 0.005) and the 33rd day of induction chemotherapy ( r = 0.408, P = 0.028), proportion of children with bone marrow MRD ≥ 0.000 1 on the 33rd day of induction chemotherapy ( χ2 = 15.42, P < 0.001), and proportion of children with gene mutations before treatment ( χ2 = 9.10, P = 0.005). Conclusions:High levels of leukocytes, neutrophils, lymphocytes, monocytes, naive lymphocytes, blood uric acid, and naive lymphocytes from the 15th to the 19th day and the 33rd day of chemotherapy, MRD on the 33rd day of chemotherapy and genotype in children with B-ALL may be associated with poor response to treatment. Clinical risk stratification is associated with gene mutation status, and gene mutation may be an important indicator of treatment response in children with B-ALL.