Clinical Characteristics and Stratified Analysis of Ph-like Acute Lymphoblastic Leukemia in Children: A Retrospective Study from China

Objective: Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (All), also known as BCR-abl1 like ALL, has a negative BCR-abl1 fusion gene, and the gene expression profile overlaps significantly with Ph+ ALL. PH like ALL contains a variety of genomic changes, including ABL class fusion (abl1, abl2, CSF1R, PDGFRB, PDGFRA); JAK pathway gene (JAK2), chemokine receptor gene (CRLF2) or MEK-ERK pathway genes, that activate kinases and cytokine receptors. Herein, we analyzed the clinical characteristics and outcome of 24 childhood Ph-like ALL cases in single center, and performed a stratified analysis.

Methods: This retrospective study of Ph-like B-ALL other than Ph+ ALL was performed in patients aged 1-16 years and treated from April 2015 to October 2020 according to the CCCG-ALL-2015 protocols in our center in China. The baseline characteristics and treatment outcomes of patients were collected. The 4-year event-free survival (EFS) and 4-year overall survival (OS) were estimated by use of Kaplan-Meier methods, and the 4-year cumulative incidence of relapse was calculated by use of a competing risk model gray test. The comparison was performed between groups by use of log rank test.

Results: We identified 24 pediatric patients with newly diagnosed Ph-like B-ALL, including 16 males (66.7%) and 8 females (33.3%). The median age was 7 years old (1-16 years old). Median leukocyte count was 31.8 (2.65-846.5) × 10^9/L。4(17%) of 24 patients were PDGFRB fusion-positive, 2 (8%) were ABL1 fusion-positive, 2 (8%) were ABL2 fusion-positive, 1 (4%) were PDGFRA fusion-positive, 1 (4%) were JAK2 fusion-positive, and 14 (59%) were CRLF2 fusion-positive. The 4-year EFS was 70.6% (95% CI, 60·5-79·1), the 4-year OS was 81·1% (95% CI, 68·6-87·5), and the 4-year cumulative incidence of relapse was 16.7%. Overall survival was significantly different between the groups (p=0·037), that were 100% in patients who were ABL1 fusion positive, 92.9% in those who were CRLF2 fusion-positive, 50% in those who were ABL2 fusion-positive, and 49% in those who were PDGFRB fusion-positive.

Conclusion: Ph-like ALL in children are characterized by an older age and a high white blood cell count at diagnosis. Ph-like ALL is a heterogeneous group of disorders, Overall survival was significantly different between the different genomic groups. Children with abl1 positive or CRLF2 positive had better survival, while those with PDGFRB positive or abl2 positive had a poor outcome.

No relevant conflicts of interest to declare.