Today, treatment results for acute lymphoblastic leukemia (ALL) look encouraging, yet 10–15% patients still end up relapsing. The success of relapse treatment is directly dependent on whether or not a tumor clone has been completely eradicated before hematopoietic stem cell transplantation (HSCT). Immunotherapy made it possible to achieve minimal residual disease (MRD) – negative remission even in refractory patients. One example of such immunotherapeutic agents is inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to the cytotoxic agent calicheamicin. We included 17 patients under the age of 18 with relapsed or refractory precursor B-cell ALL (pre-B ALL) who had been treated with InO at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of Russia from 01.10.2016 to 01.09.2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The efficacy of the therapy was assessed based on the patients’ morphological response, MRD negativity and overall survival. Treatment toxicity was assessed according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events). Statistical analysis was performed using the XLSTAT 2016 software. The majority of the patients (75%) responded to the therapy. MRD negativity was achieved in 41.2% of the study patients. The one-year overall survival rate was 40.3% (95% confidence interval 14.8–65.7). The treatment was well tolerated but 33% of the patients treated with standard-dose InO and subsequent HSCT developed veno-occlusive disease/sinusoidal obstruction syndrome. In our study, we demonstrated the high efficacy of InO both when used as a rescue therapy in patients with relapsed/refractory pre-B ALL and as a bridging therapy in patients before HSCT.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite remarkable improvements in the treatment of pediatric acute lymphoblastic leukemia over last years, relapse still carries a poor prognosis with considerable morbidity and mortality. New immunotherapeutic approaches will change the way we treated our patients and the results we had. Blinatumomab is a bispecific T-cell-engaging antibody indicated for the treatment of relapsed/refractory B-cell lymphoblastic leukemia. The use of Blinatumomab in relapsed B-cell ALL has shown promising effects, especially as a bridging tool to hematopoietic stem cell transplantation. The therapy results for patients in the high risk group remain far from optimal due to refractoriness to chemotherapy, death from infectious complications, as well as acute chemotherapy toxicity. This article demonstrates the results of our experience of using Blinatumomab in children with the high-risk group relapsed B-cell ALL treated according to the ALL-REZ 2016 protocol. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The efficacy and toxicity of innovational blocks with the use of fludarabine and clofarabine with subsequent Blinatumomab infusion are shown. And we present the efficacy of autologous CD3+ lymphocytes infusion once a week during the continuous blinatumomab therapy. Also we demonstrate the results of using Blinatumomab for the treatment of patients with refractory to the first line therapy relapsed B-lymphoblastic leukemia and patients with a second relapse of B-cell ALL. The first line therapy in these patients was carried out according to the ALL-REZ 2014 protocol. Our results show an improved reduction in minimal residual disease in patients with refractory relapsed B-cell ALL as well as an increased event free survival in children with the high-risk group relapsed B-cell ALL.

Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia (AT; Louis–Bar syndrome) are primary immunodeficiencies (PID) associated with chromosome instability and DNA repair defects that predispose individuals to an increased risk of various malignancies. In our study, we retrospectively analyzed clinical characteristics and outcomes of 28 cancer cases in 14 patients with AT and 10 patients with NBS who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January 2007 and December 2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The most common type of malignancy was mature B-cell non-Hodgkin lymphoma (B-NHL) (42%), with diffuse large B-cell lymphoma (DLBCL) accounting for 91% of all B-NHL cases. Other cases included T-cell acute lymphoblastic leukemia (ALL) (n = 3), B-cell ALL (n = 2), Hodgkin lymphoma (n = 3), NK/T-cell lymphoma (n = 1), T-cell lymphoblastic lymphoma (n = 1), peripheral T- cell lymphoma (n = 2), medulloblastoma (n = 1) epithelioid rhabdomyosarcoma (n = 1), T-cell prolymphocytic leukemia (n = 2). A total of 4 patients were diagnosed with second malignancies (2 children with AT and 2 children with NBS. The diagnosis of PID was suspected or confirmed before the initiation of cancer therapy in 62% of AT patients and in 100% of NBS patients. Treatment was given in accordance with standard protocols with chemotherapy dose modifications. A total of 93% of patients with AT and 80% of patients with NBS required dose reduction. The level of response was quite high: 81% of patients with AT and 58% of patients with NBS achieved complete remission. According to our data, the use of reduced-dose chemotherapy regimens helps to achieve an acceptable toxicity profile without reducing the overall effectiveness of treatment.