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Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among
Meagan Vacek1, Laura C Zárraga Vargas2,3, Elizabeth González Domínguez1
1Department of Pediatric Hematology-Oncology, Children's Mercy Hospital, Kansas City, MO.
Insights
Mexican and Hispanic children face higher risks of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL). This form of leukemia is linked to poor prognostic factors, highlighting ethnic disparities in pediatric cancer outcomes.
Area of Science:
- Pediatric Oncology
- Hematology
- Genetics
Background:
- Precursor B-cell acute lymphoblastic leukemia (pre-B ALL) disproportionately affects Mexican and Hispanic children, leading to poorer outcomes.
- Terminal deoxynucleotidyl transferase (TdT) expression is a key marker distinguishing immature lymphocytes in ALL from mature lymphoid malignancies.
Purpose of the Study:
- To investigate the incidence of TdT-negative pre-B ALL in Mexican, Caucasian, and US-born Hispanic children.
- To correlate TdT expression with patient characteristics and prognostic factors in pediatric ALL.
Main Methods:
- A multisite retrospective study was conducted.
- Statistical analyses included Fisher exact test for categorical variables and Wilcoxon rank-sum test for continuous variables.
- TdT expression was assessed in relation to National Cancer Institute risk, hypodiploidy, and KMT2A gene rearrangement.
Main Results:
- TdT-negative pre-B ALL was significantly associated with National Cancer Institute high-risk disease (P=0.014), hypodiploidy (P=0.001), and KMT2A gene rearrangement (P=0.0012).
- Mexican children exhibited the highest incidence of TdT-negative ALL compared to Caucasians and US Hispanics (P<0.001).
- Increased incidence of poor prognostic features was observed in Mexican children with TdT-negative ALL.
Conclusions:
- Significant racial and ethnic differences exist in TdT-negative expression, genomic alterations, and leukemic ploidy in pediatric ALL.
- The findings underscore the need for culturally sensitive approaches and targeted research to address disparities in ALL outcomes among Hispanic and Mexican children.
Abstract:
Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.
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