A New and Cost-Effective Approach to Risk Stratification for Children with Precursor B-Cell Acute Lymphoblastic Leukemia Based on Competing Outcomes

Author:

Bonakchi HosseinORCID,Kuhestani Dehaghi Bentolhoda,Hosseini-Baharanchi Fatemeh SadatORCID,Parkhideh Sayeh,Farhangi HamidORCID,baghestani Ahmad rezaORCID

Abstract

Background: Acute lymphoblastic leukemia (ALL) is a malignancy of the white blood cells characterized by its rapid and aggressive progress that needs immediate treatment. ALL could affect both adults and children. Various patient- and disease-related factors may be involved in ALL patients’ prognosis. Therefore, it is critical to identify important risk factors related to the competing outcomes of patients with ALL. Objectives: This study aimed to stratify the risk of outcomes of children with precursor B-cell ALL using demographic characteristics, laboratory characteristics, and extramedullary diseases. To achieve this goal, we used the best competing risks model to make an appropriate decision for children's treatment according to this classification. Methods: In this retrospective cohort study, 393 patients with ALL were included. ALL with B cell origins (CD20, CD19, CD10, and CD22 positive markers) was differentiated using flow cytometry. Complete remission was defined by a lymphoblast count of less than 5% in the bone marrow, presence of no blasts in cerebrospinal fluid (CSF), as well as complete disappearance of clinical symptoms. Patients with ALL were treated based on Berlin-Frankfurt-Münster (BFM). Competing outcomes were first-relapse and non-relapse mortality, respectively. Risk factors affecting competing outcomes were assessed based on a fully specified sub-distribution model. Results: Five-year estimates for overall survival and event free survival were 75% (95% CI: 69 - 79%) and 71% (95% CI: 66 - 75%), respectively. Five-year incidence rates for first-relapse and non-relapse mortality in children were 11.4% (95% CI: 8.32 - 15.16%) and 17.6% (95% CI: 13.98 - 21.67%), respectively. Moreover, according to the results, children with WBC > 50000, hemoglobin 8, and tumor lysis syndrome for the first-relapse outcome, and children with central nervous system (CNS) involvement and tumor lysis syndrome for the non-relapse mortality (NRM) outcome were considered as high-risk groups. Conclusions: We found that extramedullary diseases could have a crucial role in the risk stratification of children with precursor B-cell ALL. Therefore, for a targeted and effective treatment of high-risk children, in addition to chemotherapy, using appropriate PI3K pathway inhibitors, JAK2 pathway inhibitors, and antibody-based immunotherapy is recommended to reduce minimal residual disease and, consequently, mortality rate.

Publisher

Briefland

Subject

Pediatrics, Perinatology and Child Health

Reference48 articles.

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