Clinical and molecular characteristics of paediatric mature B-cell acute lymphocytic leukaemia and non-Hodgkin lymphoma with bone marrow involvement: A joint study between the CCCG leukaemia and lymphoma groups.

in British journal of haematology by Jie Zhao, Tian-Feng Liu, Ke-Fei Wu, Liang-Chun Yang, Xue-Ju Xu, Jun Lu, Jing-Bo Shao, Fu Li, Fu-Tian Ma, Xia Guo, Hui Li, Ai-Guo Liu, Ning-Ling Wang, He-Ping Shen, Yang Li, Si-Xi Liu, Chang-Da Liang, Shu-Hong Shen, Yong-Jun Fang, Yi-Jin Gao

TLDR

  • The study analyzed the genetic and clinical characteristics of 156 patients with mature B-ALL/B-NHL with BM involvement, identifying driver variations and associated clinical features.

Abstract

Mature B-cell acute lymphocytic leukaemia (B-ALL) is distinguished from B-cell non-Hodgkin lymphoma (B-NHL) by the arbitrariness of the 25% cut-off, and given that the percentage of bone marrow (BM) blasts can vary according to site of aspirate, we refrained from differentiating mature B-ALL from B-NHL with BM infiltration. A total of 156 patients from the Chinese Children Cancer Group with BM blasts of more than 5% and consistent with immunophenotypic features of mature B cells were included in this study. The 2-year progression-free survival, 2-year event-free survival and 2-year overall survival were 76.6 ± 3.6%, 69.7 ± 3.7% and 80.1 ± 3.3% respectively. Central nervous system (CNS) involvement, serum ferritin levels higher than four times normal and rituximab no more than two doses were associated with lower PFS. Male, bulky disease and head/neck region involvement were associated with higher rate of CNS invasion. We performed an integrative transcriptomic characterization of 36 cases. Structure variant included IG::MYC, IGH::CACS11, MEF2D::BCL9, IGH::VPS53 and ACIN1::NUTM1. SNV analysis uncovered driver variations affecting 10 recurrently mutated genes including ID3, TP53, MYC, ARID1A, SMARCA4, DDX3X, CCND3, RHOA, SMARCB1, FOXO1 and GNA13. Mature B-ALL/B-NHL with BM involvement was a heterogeneous group of malignancies in both clinical features and genetic alternations. Genetics analysis was helpful for making accurate diagnoses and guiding appropriate therapeutic strategies.

Overview

  • Mature B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (NHL) are distinguished based on bone marrow (BM) blasts percentage.
  • The study included 156 patients with BM blasts > 5% and consistent with mature B-cell immunophenotypic features.
  • The primary objective is to analyze the genetic and clinical characteristics of mature B-ALL/B-NHL with BM involvement.

Comparative Analysis & Findings

  • The 2-year progression-free survival, event-free survival, and overall survival were 76.6%, 69.7%, and 80.1%, respectively.
  • CNS involvement, high serum ferritin levels, and rituximab use were associated with lower progression-free survival.
  • Driver variations affecting 10 recurrently mutated genes were identified, including ID3, TP53, MYC, and others.

Implications and Future Directions

  • Genetic analysis is helpful for making accurate diagnoses and guiding therapeutic strategies.
  • Further research is needed to understand the genetic heterogeneity of mature B-ALL/B-NHL with BM involvement.
  • Additional studies can explore the clinical and genetic characteristics of mature B-ALL/B-NHL with BM involvement in different patient populations.