Abstract: Background The treatment of children with relapsed, refractory acute lymphoblastic leukemia (ALL) is difficult and the prognosis is poor. Bortezomib combined with chemotherapy shows promising effect, but there are few reports in China at present.Objective To investigate the efficacy and safety of bortezomib combined with chemotherapy in the treatment of children with relapsed, refractory or high-risk ALL.DesignCase series report.Methods Eleven children with relapsed, refractory or high-risk ALL who were treated with bortezomib combined with chemotherapy in the Department of Pediatrics, Peking University People's Hospital from September 2017 to September 2019 were included. Their clinical characteristics, laboratory examinations, treatment and prognosis were analyzed.Main outcome measures Overall response rate (ORR), 2-year event-free survival (EFS), overall survival (OS) and adverse events.Results Eleven children were included into the analysis, including 9 males and 2 females, with a median age of 10 (3-15) years old. We evaluated bortezomib in combination with chemotherapy in 7 cases of T-ALL, 2 cases of T lymphoblastic lymphoma stage IV, 2 cases of B-ALL. Among these patients, there were 2 cases of relapse, 4 cases of refractory and 5 cases of high-risk disease. After one course, 8 cases showed response, with an ORR of 72.7%, including B-ALL 50% (1/2) and T-ALL 77.8% (7/9). Before treatment, there were 3 cases of bone marrow non-remission and 4 cases of partial remission, and the complete remission (CR) rate was 85.7% (6/7). Before treatment, 10 cases were positive for bone marrow minimal residual disease (MRD), and all decreased after treatment, of which one case turned negative. The main adverse events were myelosuppression, infection, gastrointestinal disorder and abnormal liver function associated with combination chemotherapy. Nine cases were subsequently treated with allogeneic hematopoietic stem cell transplantation, seven of which survived without disease and two of which died of relapse after transplantation. Two cases continued chemotherapy and both died at the last follow-up. The median follow-up time was 15 (2-29) months, the 2-year EFS was 45.5±15%, and OS was 63.6±14.5%.Conclusion Bortezomib combined with chemotherapy is an effective and well-tolerated treatment option for relapsed, refractory or high-risk children with ALL.

Key words: Acute lymphoblastic leukemia, Children, Bortezomib, Combination chemotherapy