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Title: Treatment of children with relapsed and refractory acute lymphoblastic leukemia with mitoxantrone, vincristine, pegaspargase, dexamethasone, and bortezomib. Author: August KJ, Guest EM, Lewing K, Hays JA, Gamis AS. Journal: Pediatr Blood Cancer; 2020 Mar; 67(3):e28062. PubMed ID: 31724803. Abstract: BACKGROUND: The treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in children is challenging and new treatment options are needed. Bortezomib is a proteasome inhibitor with activity in pediatric acute lymphoblastic leukemia. Adding bortezomib to standard reinduction chemotherapy in relapsed and refractory pediatric ALL has produced very good response rates in prior studies. METHODS: We evaluated bortezomib in combination with reinduction therapy (ALL R3) in 10 children with relapsed or refractory ALL. Bortezomib (1.3 mg/m2 /dose) was administered to patients on days 1, 4, 8, and 11. In addition, patients received mitoxantrone, dexamethasone, pegaspargase, vincristine, and intrathecal methotrexate over 4 weeks. RESULTS: Of the 10 patients, eight (80%) achieved a complete remission (CR) or complete remission with incomplete recovery (CRi). Of the patients in CR, two had undetectable minimal residual disease by flow cytometry (<0.01%). Five patients were subsequently treated with a stem cell transplant. All eight patients that achieved CR or CRi eventually relapsed. One patient remains alive following treatment with tisagenlecleucel after relapse. Grade 3 or higher infections occurred in four out of 10 patients, and other toxicities commonly associated with bortezomib were not seen. CONCLUSIONS: In children with relapsed or refractory ALL, the addition of bortezomib to reinduction chemotherapy that includes mitoxantrone produces a complete response in the majority of cases and does not lead to excessive toxicity.[Abstract] [Full Text] [Related] [New Search]