Minimal residual disease in pediatric precursor B acute lymphoblastic leukemia and its relationship to cytogenetics and other prognostic factors

Abstract: BACKGROUND: Minimal residual disease (MRD) is the strongest prognostic indicator in acute lymphoblastic leukemia (ALL). Studying its associations with cytogenetics and various clinical and laboratory parameters may be valuable in identifying predictors for its occurrence, and thus guide risk-adapted treatment. OBJECTIVES: To determine the frequency of day-28 MRD positivity in pediatric B-ALL, and assess its associations with baseline clinical, cytogenetic risk categories, and treatment assignments. MATERIALS AND METHODS: This ambispective cohort study included 87 children with precursor B-ALL diagnosed and followed by two major Pediatric Oncology Centers in the Kurdistan Region of Iraq. All patients were screened for cytogenetic aberrations by fluorescence in situ hybridization at diagnosis, and were stratified according to UKALL-2019 criteria to receive appropriate regimens. MRD was assessed at day 28 using eight-color multiparameter flow cytometry. Associations between MRD status and various clinical and laboratory parameters were analyzed using Chi-square testing, Fisher’s exact test, and multivariate logistic regression. Kaplan–Meier analysis and Log-rank test were used to assess event-free survival (EFS). RESULTS: The enrollees had a median age of 5 years (range: 1–16), and a male-to-female ratio of 1.23:1. After receiving assigned induction therapy as per United Kingdom Acute Lymphoblastic Leukemia 2019 (UKALL-2019) criteria, MRD negativity at day-28 was achieved in 68 patients (78.2%), while 19 (21.8%) patients were MRD-positive. Univariate analysis revealed that MRD positivity was significantly associated with age ≥10 years, white blood cell ≥50 × 10 9 /L, less favorable cytogenetic risk categories, and treatment regimen allocation ( P = 0.014, 0.03, 0.0005, and 0.03, respectively). Of the latter parameters, it was only cytogenetic aberrations that remained significant by multivariate analysis ( P = 0.003). After a median follow-up of 18 months, EFS was 89.7% in MRD-negative patients compared to 84.2% in MRD-positive patients ( P = 0.332). CONCLUSIONS: Postinduction MRD positivity was encountered in 21.8% of B-ALL patients from Iraqi Kurdistan. Several MRD positivity predictors were identified; however, cytogenetic aberrations at diagnosis were the only significant MRD predictors by multivariate analysis. This underscores the crucial role of both postinduction MRD and cytogenetics to guide treatment decisions in this type of leukemia. Further studies with larger sample sizes and longer follow-up are needed to further validate these observations.