Vol 18, No 3 (2019)

Viral infections are frequent causes of failure among the recipients of the HSCT with graft TCRα/β and CD19depletion. Adoptive transfer of memory T-cells by CD45RA-depleted donor lymphocytes infusions (memory DLI) may be useful in control of viral infections. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The work reflects the retrospective data analysis of 51 patients with non-malignant disorders who had received low dose memory DLI after HSCT. Up to 3 doses of donor lymphocytes were administered. Median follow-up for alive patients was 30 (18–49) months. We did not observe any allergic reactions, septic complications after memory DLI. The cumulative incidence of a de novo acute GVHD after DLI was 10% (95% CI: 4–22). Among 41% patients (n = 21) was detected CMV in the blood. In 73% of them (n = 16) CMV was detected before first DLI. Among patients who received DLI, 53% (n = 27) had documented appearance of virus-specific lymphocytes in peripheral blood (ELISPOT assay).Thus, the infusion of memory T-cells at a dose of 25–100 αβ 103/kg body weight of the recipient for CD3+ in the case of HSCT from a haploidentical donor and 100–300 αβ 103/kg for an unrelated HSCT. Infusions of low dose memory T-lymphocytes after transplant engraftment are safe, potentially effective and constitute a simple measure to prevent infections in the setting of alpha/beta T-cell-depleted transplantation.

Diamond–Blackfen Anemia (DBA) is a rare, clinically and genetically heterogeneous disorder from the group of congenital syndromes of bone marrow failure. The purpose of this work is to identify the main medical-frequency characteristics of DBA (incidence, prevalence, mortality, cartographic analysis) in children in the Russian Federation during the observation period 2011–2016. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The Russian register of DBA patients, which had been developed and maintained since 2012 year by NMITS DGOI, was used to obtained epidemiological data and their analysis. At the end of 2018 year 141 patients from 137 families were included in the register. The average annual incidence rate of children with DBA for the Russian Federation was 0.63 ± 0.034, the average annual prevalence rate – 5.75 ± 0.87 per 100 thousand newborns born alive; mortality rate – 2.12%; the cartographic method of research showed that the largest number of patients was registered in the Central Federal District of the country, which is explained by the high population living in this district.

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia, in which the bone marrow produce increased numbers of immature abnormal megakaryoblasts. AMKL is rare both in children and adults, but is the most frequent subtype of acute myeloid leukemia (AML) in children with Down syndrome. Morphological diagnosis of this disease could be complicated, thus flow cytometry plays a crucial role in the diagnostics of AMKL. The aim of the present study was to investigate the immunophenotypic characteristics of AMKL in children. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The study group included 103 patients with AMKL. Antigen expression profile was assessed by multicolor flow cytometry. We identified three groups of patients according to different levels of CD45 expression, and in majority of patients (74%) high level of CD45 expression was detected. Significant immunophenotypic differences between these groups were found. In 56% of patients trisomy of 21 chromosome was detected. Among these patients, 86% belonged to group of high CD45 expression. Moreover, children with trisomy 21 represented the majority in the group with high level of CD45 expression (64%). Also, there were found several significant differences between patients with and without trisomy 21 within the group of high CD45 expression. This study demonstrated the wide immunophenotypic heterogeneity of AMKL. In general, the revealed diversity obviously reflects the biological heterogeneity of this AML subtype.

Diffuse sclerosing osteomyelitis of the jaw (DSO) is a rare and poorly understood disease. Nowadays treatment protocols (steroid or painkillers, corticotomy) do not capable of to get good and stabile results or are associated with the development of potentially serious side effects. The treatment algorithm developed by us, including the course treatment with bisphosphonates, was well tolerated and capable of to get clinical and radiological remission in the case of previous decortication and antibacterial therapy was done. For these reasons, this treatment protocol is not without interest and need of further investigates. The study was approved by the Local Ethics Committee of Russian Children's Clinical Hospital.

ANKRD26-related thrombocytopenia (previously known as thrombocytopenia-2) is a rare form of inherited platelet disorders. Patients with ANKRD26-related thrombocytopenia usually do not suffer from severe bleeding but have predisposition to acute myeloid leukemia and other malignancies. Patients with ANKRD26-related thrombocytopenia and their relatives need genetic consultation and long term follow-up in view of risk of malignant blood disorders. The clinical case of ANKRD26-related thrombocytopenia in two siblings is presented in this paper. Review of literary data on pathogenesis, treatment and follow-up of patients with ANKRD26-related thrombocytopenia is performed. Common questions of diagnosis and management in patients with congenital thrombocytopenias with predisposition to malignant blood disorders are also reviewed. Parents gave their permission for using personal data for clinical research and publications.

Vitamin B12 (cobalamin) deficiency in infants exclusively breastfed is usually the result of its deficiency in the mothers (vegetarians or in the presence of unrecognized pernicious anemia or malabsorption syndrome). Cobalamin is crucial for the normal development of the nervous system, the production of erythrocytes and the synthesis of DNA. The classic manifestation of its deficiency is megaloblastic anemia and, in advanced cases, pancytopenia. However, infants often present neurological symptoms (fatigue, failure to thrive, regress of developmental skills, lethargy, motor disorders), as a consequence of inadequate myelination of the brain. Cobalamin treatment is effective in the most children, however, the neurological deficit varying degrees may persist. The long-term prognosis depends on overall duration of vitamin B12 deficiency and severity of symptoms. The article presents our own interesting clinical observations. Parents gave their permission for using personal data for clinical research and publications.

Invasive aspergillosis (IA) is a life-threatening complication in pediatric patients with hematological malignancies. The highest incidence rates of IA were found in pediatric patients with acute myeloid leukemia (AML). We presented a case of successful treatment of IA in a patient with debut of AML with Down syndrome, analysis of IA cases in children with AML according data of the register and a literature review. 46 pediatric patients with IA were included, among them 16 (34.7%) with AML. In 3 (18.75%) pts AML was diagnosed in presentation of AML. Risk factors of IA were prolonged neutropenia (100%) and lymphocytopenia (81%). The most common clinical signs were: fever > 38.5 ºС (93.7%), cough (75%) and respiratory failure (43.7%). The lung involvement was diagnosed in 93.7% of pts, more than 2 sites of IA – in 12.5%, endophthalmitis – in 6.25%. Typical imaging finding was «halo sign» – 37.5%. According received results «probable IA» was diagnosed in 87.5% of pts and «proven» in 12.5%. Antifungal treatment received 100% of patients, with voriconazole only – 50%, combined antifungal therapy – 33.3%. Overall 12-week survival was 87.5%. Parents patients agreed to use personal data in research and publications.

Primary immunodeficiencies (PIDS) are genetically caused heterogeneous diseases of the immune system. One of the genetic phenomenon affecting the phenotypic diversity of PIDS is a reverse somatic mosaicism (RM) observed in different groups of PIDS. The majority of RM cases are described in patients with Wiskott–Aldrich syndrome (WAS). Despite the fact that PM does not always lead to a mild form of the disease, the presence of this phenomenon can cause the delay of diagnosis and start of the appropriate treatment. This article presents the case of a patient with Wiskott–Aldrich syndrome with a reverse mutation in the WAS gene. Parents gave their consent to use information about the child in the article.

Platelets perform numerous important functions not only in the process of normal functioning of hemostatic system, but also in other physiological processes, such as: vessel wall integrity regulation, wound healing, inflammatory response. Its malfunction can be found in various diseases and conditions (including oncohematological disorders, solid tumors, inflammatory diseases, sepsis, autoimmune disorders), is triggered by injury or medications and can lead to dangerous consequences, such as bleeding and thrombosis. However, platelets functional activity quantity assessment tools are extremely limited, the perception what platelet functional activity is about is also quite unclear. This review considers platelets function, its' abnormalities, possibilities for its' assessment by existing methods as well as promising directions for their development.

Complement is a part of the immune system which provides host cells with protection against pathogen cells and particles. It is activated when a pathogen invasion is detected. The results of numerous investigations have led to growing realization of the important role of this system in maintaining normal organism homeostasis. This review summarizes a modern view on the complement system.