Combined adoptive immunotherapy with Blinatumomab and donor lymphocyte infusions in children with relapsed/refractory B-ALL after allogeneic stem cells transplantation

Abstract

Allo-HSCT is potential curative option for high-risk pediatric B-cell acute leukemia (B-ALL), nevertheless about 30-70% of patients relapsed after allo-HSCT. Patients with relapsed/refractory (r/r) B-ALL have a dismal prognosis with 3-year probability overall survival (OS) about 20%. In this study we firstly appreciated efficacy and safety of combined adoptive immunotherapy with bispecific T-cell engager Blinatumomab and donor lymphocyte infusions (DLI) for 17 children underwent allo-HSCT and having relapse or minimal residual disease (MRD) after that. Fifteen (88%) of patients achieved a complete remission within the first 2 cycles of treatment with blinatumomab and DLI. The median relapse-free survival was 9.1 months (95% CI, 3.0 to 37.2 months) in patients who achieved CR, with the median duration follow up 13,3 months (95% CI, 10.0 to 30.3 months). The median overall survival for all patients was not reached at a median follow-up of 13.3 months (95% CI, 8.8 to 27.4 months). The Kaplan-Meier estimate overall survival was 76.5% (95% CI, 44%-92%) at a median follow-up time 13,3 months. Three children (18%) experienced drug-related adverse events grade 3 and two children (12%) had clinically significant induced "graftversus-host disease" (GVHD). There were no fatal cases due to the therapy. Further immunotherapy options for r/r pediatric ALL may include repeated courses of combined adoptive immunotherapy, monotherapy of escalated DLI, chimeric antigen receptor T-cell therapies, checkpoint inhibitors or undergo second allo-HSCT.

The prophylaxis of severe hemophilia A with inhibitors in children in the Republic of Belarus: a 12-year experience

“…Из них 6 человек имели ответ на терапию, однако долгосрочные результаты были неблагоприятными ввиду рецидива заболевания и развившихся осложнений [4]. Профилактический подход с использованием ИДЛ и гипометилирующих агентов потенциально эффективен у взрослых пациентов с ОМЛ и миелодиспластическими синдромами, но данных у детей, особенно с ЮММЛ, недостаточно [6,16].…”