Introduction. Since 2009, the RALL Group has been treating Ph-positive ALL by protocols based on a continuous chemotherapeutic approach with TKI combination. Based on the results of the studies received in 2011, a protocol was developed for ALL-2012 for the treatment of Ph-positive ALL, in which chemotherapy was de-escalated.

Aim. The aim of the study was to compare the efficacy and long-term results in patients treated by  ALL-2009 protocol with TKI and ALL-2012 protocol.

Materials and methods. The study included patients with newly diagnosed Ph-positive ALL who received therapy from 2009 to 2017 in one of 3 centers: 12 patients who were treated according to the ALL-2009 protocol with TKI, and 23 patients treated according to the ALL-2012 protocol. The study does not include patients who have been treated in other centers.

Results. Two deaths were recorded on each protocol: ALL-2009 with imatinib – 1 (8%) in induction and  1 (8%) in consolidation; ALL-2012 – 1 (4%) patient in induction and 1 (4%) in consolidation treatment. There were no significant differences in the frequency of complete remissions after induction courses, and their incidence was 83% and 87%, respectively. In group of patients that were treated by ALL-2009 protocol with ITK, the frequency of complete molecular remission after 2 courses of induction therapy (the 70th day of the protocol) was 43% (3 of 7 patients), and those who received therapy by ALL-2012 protocol – 55% (in 11 of 20 patients).

The differences in the frequency were not statistically significant (p > 0.05).

Refractory of the disease was detected in 1 (8%) of the patients on the ALL-2009 protocol with ITK and in  1 (4%) of the patients on the ALL-2012 protocol. In all patients with Ph-positive ALL (n = 35) the overall survival was 55% and the disease-free survival was 40%. Fourteen (40%) of 35 patients underwent transplantation of hematopoietic stem cells.

The conclusion. According to the retrospective multicentre study of the RALL, it was shown that  de-intensification of chemotherapeutic treatment against the background of constant therapy of TKI did  not affect the effectiveness of therapy.

In our research the comparison of different regimes of mobilization of HSC were carried out. First regime: conduct stimulation of granulopoiesis using granulocyte colony-stimulating factor (GCSF). Other regimes: of mobilization with chemotherapy (cyclophosphamide or cytarabine). The efficiency and the toxicity were  assessed. The grafts with satisfactory cellularity were obtained in 91% patients. The number of CD34⁺ cell/ml were obtained in the first apheresis and from whole mobilization in patients with complete remission (CR) were more than the number of in patients with < CR. CD34⁺ cell number in the blood correlate well with total number of CD34⁺ yielded from apheresis in same day. The number of CD34⁺ cells/microliter yielded from mobilization was more in group with сhemomobilization than in group with GCSF only. In comparison two groups of сhemomobilization: the number of CD34⁺ in peripheral blood in day apheresis was more in group with  AraC-GCSF; р = 0.173. There was revealed lesser toxicity in group with AraC-GCSF.

The aim of this study was to evaluate indications, efficacy and rate of hepatic dysfunction in patients with hematological malignancies treated with micafungin.

Material and Methods. Micafungin was administered in dose of 100 mg intravenously once daily.

Results. Primary prophylaxis with micafungin was performed in 16 (46%) of 35 patients, all of them were recipients of allogeneic hematopoietic stem cells (allo-HSC), 81% – had graft-versus-host disease (GVHD) and  received prednisolone in dose of ≥ 1 mg/kg daily. Median duration of prophylaxis was of 27 (4–105) days, in 14 (88%) patients – 7 days and more, in 2 (12%) – less than 7 days. Invasive aspergillosis (“probable”) occurred in 1 (7%) of 14 allo-HSCT recipients under micafungin treatment for ≥ 7 days. Micafungin treatment was initiated in 19 (54%) of 35 patients with median duration of 13 (3–32) days. Indications for micafungin treatment were candidemia (n = 7), hepatosplenic candidiasis (n = 4), empirical therapy (n = 6) and preemptive therapy. Fatal outcome was in 2 of 7 patients with candidemia, other patients had favorable outcome. Prior to the beginning of the treatment with micafungin 21 (60%) of 35 patients had elevation in one or more liver function tests.  During micafungin treatment liver function parameters decreased in patients with initially elevated levels of these parameters and remained in reference ranges in patients with previously normal values.

Conclusion. The study demonstrated the efficacy of micafungin both for prophylaxis of invasive  mycoses in allo-HSCT recipients with GVHD and the treatment of proven and suspected invasive candidiasis.  We confirmed the safety of the micafungin use in patients with hematological malignancies.

Pathogen inactivation treatment of platelet concentrates improves the transfusion safety. The influence of the pathogen inactivation on the platelet activation remained unclear. The aim of the study was to  evaluate the changes of the platelet activation markers in donor platelets concentrates during the storage after the inactivation of pathogens by amotosalen and ultraviolet A. By flow cytometry CD62P (P-Selectin) and activated GPIIb/IIIa surface expression were estimated with a mouse-anti-human IgG1 CD62-PE  antibodies and mouse-anti-human GPIIb/IIIa-FITC (PAC-1) antibodies. In platelet concentrates during the storage the fraction of the spontaneously activated platelets increased and fraction of the platelets capable of specific activation under the action of the ADP agonist decreased. The pathogen reduction did not  affect the ability of platelets to specific activity, but led to an increase in the fraction of the spontaneously activated platelets. Replacement of plasma with a solution SSP⁺ led to the increase in the proportion of spontaneously activated platelets, but during prolonged storage has contributed to the preservation of the fraction of functionally active platelets.

The hemorrhagic syndrome is the relative contraindication for the central venous access. However, in the clinical practice, many patients with hemorrhagic syndrome need a long-term vascular access.

Purpose of the study was to investigate the use of Peripherally Inserted Central Catheters (PICC)  in patients with severe hemostatic disorders.

Results. In total, 16 PICCs were implanted in 12 patients with hemorrhagic syndrome (6 hemophilia  patients, 4 of them with inhibitor to FVIII, 1 patient with breast cancer and Willebrand disease, 3 patients with acute promyelocytic leukemia, 1 patient with multiple myeloma and 1 patient with myelodysplastic  syndrome). Hemostasis was provided by recombinant activated factor VII (rFVIIa), platelet and cryoprecipitate transfusions. The period of use of PICCs varied from 5 days to 1 year and 3 months.  There were no thrombotic and infectious complications. PICC can be considered as a method of choice for long-term vascular access  in patients with hemorrhagic syndrome.

The aim of the study was to evaluate the frequency of Human Herpes Virus 6 (HHV6) infection in  immunocompromised patients and to analyze the efficiency of the antiviral treatment. In retrospective study 273 patients with hematological disorders were analyzed from Jan 2013 to Jul 2017 (72 patients with acute lymphoblastic leukemia (ALL), 141 case – with acute myeloid leukemia, 15 cases with high-grade B-cell lymphoma (BCL), 45 aplastic anemia patients. 25 patients underwent autologous stem cell transplantation  (19 with ALL, 6 with BCL). DNA of HHV6 was detected in 32.9% of patients, including 11 patients after transplantation. However, the detection of HHV6 with clinical symptoms was identified only in 26 (9.5%) of 273 patients. Febrile neutropenia, hemorrhagic cystitis, enteropathy, pneumonia, 1 case of encephalitis and 1 case of severe cutaneous HHV6 lesion were detected as clinical manifestations of the infection. The importance  of prolonged intravenous antiviral treatment was demonstrated. Thus, HHV6 DNA is detected in large percent of cases in hematological patients but its clinical manifestation is not seen very often. The early prolonged and adequate treatment reduces the risks of complications.

Modern therapy of hematological diseases requires the intensive use of maintenance of high-quality and safe platelet concentrate (PC) transfusions. Transfusions of PCs are the main method of arresting hemorrhagic complications in thrombocytopenia. The highest need to PC transfusions is noted in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), acute leukemia and after transplantation of hematopoietic stem cells (THSC). Multiple PC transfusions may be a risk factor for the development of alloimmunization by leukocyte (HLA) and specific platelet (HPA) antigens. It is advisable to carry out such PC transfusion in alloimmunized patients on the basis of the individual selection with the use of immunological compatibility tests of donor-recipient pairs. In cases of multiple alloimmunization, the selection of a “donor-recipient” pair is difficult or impossible. Circulating alloantibodies and autoantibodies can be eliminated by plasmapheresis.

Infection is one of the leading causes of the mortality and morbidity. Neutrophils protect the body against pathogenic microorganisms. However, the contribution of neutrophils in the development of the infectious process was underestimated. In addition to phagocytosis, neutrophils can mediate extracellular degranulation, release of  extracellular chromatin, nuclear protein and serine proteases and form neutrophil extracellular traps NETs. NETs can capture pathogens, cause endothelial dysfunction and pro-inflammatory immune responses. The phenomenon of NETs is a relatively new form of programmed cell death (NETosis). NETosis has a high potential for the further study of the pathogenesis of inflammation and the search for effective methods of treating infections. This review focuses on modern data on the basic protective strategies of neutrophils against bacterial infections and their contribution to the pathogenesis of proinflammatory responses. Approaches to pharmacological modulation of different antimicrobial mechanisms of neutrophils are discussed.

Currently, methods of therapeutic the treatment of polycythemia vera (PV) are: prophylaxis of thrombotic complications with acetylsalicylic acid; erythrocytapheresis; cytoreductive therapy; treatment of thrombotic complications; therapy in special conditions  (pregnancy, surgery). The first line of the treatment at a young age is interferon α, in the older age group is hydroxycarbamide. In 15–25% of cases, these drugs have low efficiency and poor tolerance. The transition to another line is indicated if the therapy is ineffective or patient is intolerant of the therapy. Results of clinical trials have proved the effectiveness of ruxolitinib,  JAK2 inhibitor,  in the management of splenomegaly and constitutional symptoms in patients with primary myelofibrosis and PV. A review of the literature and a description of the clinical case of the effective treatment of the PV patient ruxolitinib is presented.