New guidelines on diagnosis and treatment of a primary immune thrombocytopenia (ITP) in children and adults, on the basis of modern pathogenesis conceptions and considering possibilities of hematological practice in Russia are presented. Guidelines are based on a consensus of international and Russian experts on ITP. Diagnostic features of ITP are noted and various I, II and III lines treatment, including new effective medical products which have recently appeared in Russia, in particular, trombopoietin receptor agonists (romiplostim, eltrombopag), considerably expanded conservative treatment possibilities are offered. The presented guidelines can help hematologists to develop individual schedule for each given patients with ITP and to improve patients quality of life.

Russian Interregional Register of hematopoietic stem cell transplantation was established in 2000. 11 transplant centres from 7 Russian cities are including in Register now. In this analysis we applied transplant activity survey data from 01.01.1996 to 31.12.2006. A total 1118 transplants (846 – autologous and 272 – allogeneic) were carried during this period.

Background Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies. Methods This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered (NCT01254630 and EudraCT 2010-023156-89). Findings Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI −1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI −17·8 to 41·3). Interpretation The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies. Funding Merck & Co, Inc.

По инициативе Российского национального гематологического общества, исследовательской группой по изучению идиопатической тромбоцитопенической пурпуры (первичной иммунной тромбоцитопении) ИТП разработаны клинические рекомендации по ее диагностике и лечению. Целью рекомендаций является стандартизация диагностических и лечебных подходов при ИТП в России. Используемые методологические подходы основаны на принципах доказательной медицины, в их основе лежат рекомендации Российского совета экспертов по диагностике и лечению больных первичной иммунной тромбоцитопенией и российский опыт ведения больных ИТП, а также руководство Международной рабочей группы по изучению первичной иммунной тромбоцитопении (International Working Group), решения Международного консенсуса по диагностике и лечению ИТП и рекомендации европейских и американских обществ гематологов по изучению данного заболевания. Национальные клинические рекомендации разработаны многоцентровой исследовательской группой по изучению ИТП в России. В их разработке принимали участие ведущие специалисты 8 гематологических центров РФ.

The research group for studies of idiopathic thrombocytopenic purpura (ITP) has developed clinical recommendations for the diagnosis and treatment of this disease. The aim of the recommendations is standardization of the diagnostic and therapeutic approaches in Russia. The current methodological approaches proceed from the conclusive medicine philosophy and are based on the recommendations of the Russian Expert Council for the diagnosis and therapy of patients with primary immune thrombocytopenia and the experience gained in the treatment of ITP patients (primary immune thrombocytopenia) in Russia, as well as on recommendations of the International Working Group for studies of primary immune thrombocytopenia, decisions of the International Consensus on ITP diagnosis and therapy, and recommendations of the European and American Societies of Hematologists for ITP studies. The recommendations are developed by the multicenter research group for ITP studies. Working groups from 8 leading institutions of Russia contributed to the development of clinical recommendations.

Primary immune thrombocytopenia (ITP) is a rare (orphan) blood disease. Most frequent manifestations of ITP are purpura, petechiae and bleedings with many patients have either no symptoms or minimal bleedings manifestation. The management of ITP varies widely and must be based on current international recommendations and individual assessment of clinical course. The paper presents the results of interim analysis of clinical course and therapeutic approaches in the Russian register of ITP patients with immune thrombocytopenia and literature review about ITP treatment approaches.

Diabetes mellitus (DM) is characterised by relative or absolute insulin deficiency. The currently available treatment methods for DM cannot provide normal blood glucose level without hypo- or hyperglycaemia episodes, thus failing to completely prevent the development of diabetic complications. Replacement of ?-cells (transplantation of the pancreas or ?-cells) is accompanied by complications and requires life-long immunosuppressive therapy that is not always followed by restoration of insulin independence; there is also a substantial deficit of donors. Stem cells do not cause such negative effects and can be used in therapy to avoid such problems. Allogeneic stem cell transplantation is complicated by immune rejection of a transplant, whereas the use of embryonic stem cells is associated with ethical concerns, complicated cell line selection, and risk of teratoma formation. The present review focuses on therapeutic pathways of autologous transplantation of tissue stem cells in order to restore the ?-cell pool, for immune reconstitution and modulation of the immune response in DM patients.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life‑threatening clonal hematological disorder caused by an acquired mutation in the phosphatidylinositol glucan (PIG)-A gene. PNH is characterized by chronic intravascular hemolysis, marrow failure, thrombophilia and other severe clinical syndromes. Until recently, the treatment of PNH has been symptomatic with blood transfusions, anticoagulation and supplementation with folic acid or iron. The only potentially curative treatment is allogeneic stem cell transplantation, but this has severe complications with high mortality rates. A new targeted treatment strategy is the inhibition of the terminal complement cascade with anti‑C5 monoclonal antibody (eculizumab). Eculizumab has shown significant efficacy in controlling of intravascular hemolysis resulting in improving quality of life and survival.

Primary immune thrombocytopenia (ITP) is a rare (orphan) blood disease. Most frequent manifestations of ITP are purpura, petechiae and bleedings with many patients have either no symptoms or minimal bleedings manifestation. The management of ITP varies widely and must be based on current international recommendations and individual assessment of clinical course. The paper presents the results of interim analysis of clinical course and therapeutic approaches in the Russian register of ITP patients with immune thrombocytopenia and literature review about ITP treatment approaches.

Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT). The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP) with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l) due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l) with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg/kg weekly with completion of hemorrhagic syndromes and achieving 20 × 109/l blood platelet counts. Romiplostim was continued in dose 5 mkg/kg/wk during 2 weeks and stable platelet counts > 30 × 109/l was achieved. The romiplostim efficacy in these patients supports the use of TPO-agonists in patients after allogeneic BMT who developed severe thrombocytopenia due to TTP, CMV infections, acute GVHD and other posttransplant complications.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal blood disorder caused by somatic mutation of the phosphatidylinositol glycan complementation group A gene (PIG-A) in a hematopoietic stem cell. PNH is characterized by chronic intravascular hemolysis, bone marrow failure, thrombosis, renal dysfunction and other severe clinical syndromes. These clinical guidelines include definition, classification, methods and diagnostic criteria of PNH, indications for screening, optimal treatment including targeted therapy with eculizumab, bone marrow transplantation and symptomatic therapy.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal blood disorder caused by somatic mutation of the phosphatidylinositolglycan complementation group A gene (PIG-A) in a hematopoietic stem cell. PNH is characterized by chronic intravascular hemolysis, bone marrow failure, thrombosis, renal dysfunction and other severe clinical syndromes. These clinical guidelines include definition, classification, methods and diagnostic criteria of PNH, indications for screening, optimal treatment including targeted therapy with eculizumab, bone marrow transplantation and symptomatic therapy.