The long-term outcomes and risk factors for precursor B-cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: Experiences from multiple centers

Specific fusion genes play important roles as risk factors in the pediatric B-cell acute lymphoblastic leukemia (B-ALL) population. In addition, these fusion genes are used for determination of patient treatment. However, the risk factors and long term outcomes in B-ALL patients without common fusion genes have not been well demonstrated, and thus our aim was to evaluate this patient population. We retrospectively analyzed clinical and laboratory findings, treatment responses, and outcomes in pediatric patients with B-ALL without specific fusion genes. Moreover, we analyzed whole-exome sequencing and/or RNA sequencing data from bone marrow (BM) relapsed patients. Overall, 283 patients were enrolled in the study. Traditional parameters and treatment responses at different time points (TP) were evaluated to classify risk groups and adjust treatment strategy. Statistical analysis showed that 49 (17.31%) patients relapsed, while treatment-related mortality was found in 11 (3.89%) patients. Ten-year prospective event-free survival (pEFS) was 78.2 ± 2.5%. Adverse and unreported genetic abnormalities were discovered in 25 BM relapse patients. Univariate analysis revealed that good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Moreover, multivariable analysis of outcomes and hazard ratios determined that positive MRD level was the key risk factor. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy. Next generation sequencing has proven to be a useful technique in identifying molecular risk factors in cases without common specific genetic alterations.