Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

Chao Gao; Shu-Guang Liu; Zhi-Xia Yue; Yi Liu; Jing Liang; Jun Li; Yuan-Yuan Zhang; Jiao-Le Yu; Ying Wu; Wei Lin; Hu-Yong Zheng; Rui-Dong Zhang

doi:10.1186/s12935-019-1013-9

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

Cancer Cell Int. 2019 Nov 14:19:293. doi: 10.1186/s12935-019-1013-9. eCollection 2019.

Authors

Chao Gao^#¹, Shu-Guang Liu^#¹, Zhi-Xia Yue¹, Yi Liu¹, Jing Liang¹, Jun Li¹, Yuan-Yuan Zhang¹, Jiao-Le Yu¹, Ying Wu¹, Wei Lin¹, Hu-Yong Zheng¹, Rui-Dong Zhang¹

Affiliation

¹ Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing, 100045 China.

^# Contributed equally.

Abstract

Background: Although leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes.

Methods: This study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19⁺CD10^- pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children's Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed.

Results: KMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1 ⁺ patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively).

Conclusions: Pediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.

Keywords: Acute lymphoblastic leukemia; Biological characteristics; Pediatric; Pro-B cell; Prognostic factor.