Clinical impact of early minimal residual disease detection at day 15 in precursor B-childhood acute lymphoblastic leukemia: an Egyptian experience

Abstract

Abstract Background Chromosomal abnormalities in childhood acute lymphoblastic leukemia (ALL) are well-established prognostic markers and useful tools for minimal residual disease (MRD) assessment. This study aimed to stratify high-risk precursor B-childhood ALL (pre-B-ALL) patients according to standard prognostic factors (age and total leucocytic count), fluorescence in situ hybridization (FISH) analysis for these cytogenetic abnormalities [t (9;22) BCR/ABL, t(1;19)TCF3/PBX1, and 11q23 MLL gene rearrangement], and MRD status at day 15. Besides, we aimed to demonstrate the relation of these prognostic factors (standard and cytogenetic risk groups) to patients’ outcome at day 15 of induction therapy as well as exploring the impact of early MRD assessment during remission induction compared to other prognostic factors together with the ability to tailor investigations as needed especially in places with limited health resources without compromising the outcome. Seventy-two newly-diagnosed Egyptian children with pre-B-ALL, aged 6 months to 15.5 years, registered from February 2016 to February 2018 were included. They were treated according to the modified Children’s Oncology Group (COG) protocol. Patients were classified into (a) standard and high-risk groups according to standard prognostic factors. (b) Patients with the studied cytogenetic abnormalities and patients without the studied cytogenetic abnormalities. (c) Good outcome (negative MRD) and bad outcome (positive MRD) groups according to day 15 MRD status. Results The studied cytogenetic abnormalities were identified in 22.2% of patients, all of them were in the high-risk group, and 75% of them had a bad outcome (positive MRD) at day 15 of induction therapy. Conclusion Patients with favorable presenting features (standard risk) and undetectable MRD after 2 weeks remission induction therapy would not be in need to advanced molecular studies, while these studies should be considered for patients with high-risk presenting features and high levels of MRD after 2 weeks remission induction therapy. Therefore, this could provide a cost-effective guideline in countries suffering from financial challenges without affecting the outcome

Keywords

• Cytogenetic abnormalities
• Day 15 MRD
• Precursor B-childhood ALL
• Prognostic factors