Search

In 1990 to 2005, a total of 138 hematopietic stem cell transplantations (HSCT) were made in patients with high risk group of acute myeloblastic leukemia (AML) (auto-HSCT in 20 patients, related allo-HSCT in 18, unrelated allo-HSCT in 20) and acute lymphoblastic leukemia (ALL) (auto-HSCT in 13 patients, related allo-HSCT in 24, unrelated allo-HSCT in 43). The patients' age was 2 to 55 years. Five-year relapse-free survival after auto-HSCT in the 1st-2nd remissions in AML was 40%; 8-year one was 30% in patients with ALL (including 3 patients with Ph+). In patients aged less than 21 years with acute leukemias, 5-year overall survival after related and unrelated donor allo-HSCT was 38 and 44%, respectively. Both allo-HSCT modes had the similar spectrum of complications in the early period (as long as 100 days). In patients with AML and ALL, 5-year overall survival depended on the stage of disease at the moment of allo-HSCT performance (52 and 5.9% in ALL and 62.5 and 27.3% in AML, remission and relapse, respectively). Auto- HSCT in ALL and AML is an effective method for remission consolidation and may be regarded as an alternative if the patient has no related or unrelated donor. The efficacy of allo-HSCT from a related or unrelated donor in acute leukemia depends on the stage of disease at the moment of its per- formance, which determines the likelihood of development of a relapse and different complications (toxic, infectious, graft rejection, etc).

Acute graft-versus-host disease (GFHD) and graft rejection reaction (GRR) early in the post-transplantation period are main complications of allogeneic transplantation of hematopoietic stem cells. We analyzed the incidence of principal early complications in 109 patients with various oncohematologic diseases who underwent 112 allogeneic transplantations of hematopoietic stem cells from related and unrelated donors with myeloablative and non-myeloablative regimens of conditioning with and without use of anti-monocyte globulin. Application of anti-monocyte globulin provides effective control of acute GFHD without increment of disease relapsing risk and lowers the incidence of GRR to 7%. So, results of our study showed that usage of anti-monocyte globulin with conditioning regimens for patients who habe undergone allogeneic transplantation of hematopoietic stem cells, allows to effectively decrease the incidence of early posttransplantation complications. Consequently, that increases the 4-year overall survival of these patients as compared with patients who did not undergo the use of anti-monocyte globulin.

Overall survival and relapse rates in 62 patients after allogeneic hemopoietic stem cells transplantation according to posttransplantation chimerism values are presented. Significant differences in 5-year overall survival rate have been found in patients with complete donor and mixed chimerism on days 30 and 100 after transplantation with myeloablative conditioning regimens. The influence of chimerism in different time point after transplantation for relapse rate is shown.

Diseases with eosinophilia the pathogenesis of which is unclear are of particular clinical significance among hematological malignancies. These include acute and chronic graft versus host disease (GVHD) associated with eosinophilia, hypereosinophilic syndrome and chronic myeloid leukemias, Hodgkin's and non-Hodgkin's lymphomas. The role of eosinophils and mast cells intracellular proteins in proliferative diseases is unknown. The objective of the investigation was to study the significance of tryptase and eosinophilic cationic protein (ECP) measurements in patients with chronic GVHD and hematological malignancies. Thirty two patients with verified oncohematological diseases (a study group) — 6 patients with chronic GVHD after allogeneic hemopoietic stem cells transplantation, 18 with asthma and 8 with solid tumors - were included in the study. The serum concentrations of tryptase and ECP were measured by immunofluorescence assay. Elevated ECP levels were found in patients with GVHD (p < 0.03) and in those with lymphoproliferative diseases (p = 0.007) as compared to the nonhematological group (p < 0.03). Increased tryptase level was recorded in patients with GVHD and lymphoproliferative diseases as compared to those with solid tumors and nonhematological disorders (p = 0.03), as well as in the GVHD versus lymphoproliferation groups (p < 0.05). A direct correlation between ECP concentration and the eosinophils count in patients with lymphoproliferative diseases (r = 0.9; p = 0.000001) was found. The authors have concluded that measurement of soluble eosinophilic proteins levels and mast cell enzymes is reasonable to diagnostics and monitoring of various hypereosinophilic states in patients with chronic GVHD and hematological malignancies.

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal proteins pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: 1) limited knowledge about the MGRS among hematologists and nephrologists; 2) lack of necessary diagnostic resources in most health-care facilities; 3) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts leading nephrologists and hematologists of Russian Federation on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy, 1516 of March 2019, Pavlov First Saint Petersburg State Medical University. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.

The pathogenetic relationship of kidney damage and an aberrant clone of the B-cell line producing nephrotoxic monoclonal immunoglobulin underlies the concept of “monoclonal gammopathy of renal significance” (MGRS). Herein the aberrant clone does not reach the criteria necessary for initiating antitumor therapy according to oncohematological indications. MGRS is a new nosology in modern nephrology and oncohematology. Monoclonal protein’s pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most health-care facilities; iii) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. In order to overcome these limitations, leading oncohematologists and nephrologists of the Russian Federation on behalf of professional communities at the end of 2019 published a conciliation document: “Monoclonal gammopathy of renal significance: Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment”. Consensus document comprises the opinion of experts – leading nephrologists and hematologists of Russian Federation – on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia “Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy”, 15–16 of March 2019, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia. Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses which we present here.

Background. Ewing sarcoma (EWS) is a second most common pediatric bone tumor. About one quarter of all patients belong to a high-risk group characterized by a poor prognosis. In spite of high-dose chemotherapy (HDCT) with autologous hemopoietic stem cell transplantation (auto-HSCT) being traditionally viewed as a possible option for high-risk patients, there is stills no consensus on indications for this method in EWS patients.Study objective: to evaluate the HDCT effectiveness and most important prognostic factors in a prospective cohort of high-risk EWS patients. Materials and methods. A total of 73 EWS patients receiving treatment in R.M. Gorbacheva Memorial Institute were included in the study. All patients were characterized by one or several high-risk features: local (primary tumor volume >200 ml, axial localization, poor response to chemotherapy; n = 55; 76 %), primary disseminated disease (n = 58; 80 %), first chemoresponsive relapse (n = 7; 9 %). All patients received a myeloablative consolidation regimen consisting of busulfan 16mg/kg and melphalan 140mg/m2. In patients with primary disseminated disease an additional evaluation according to risk scale by R. Ladenstein et al. was performed. Based on risk points all patients were stratified as standard (n = 20), high (n = 26), and ultrahigh risk (n = 12).Results. The 5-year overall and event-free survivalfor a whole studied cohort were 40 and 37 %, accordingly. In patients with high-risk localized disease the 5-year overall and event-free survival were 48 and 45 %, accordingly. The HDCT regimen was characterized by acceptable toxicity. The main non-hematologic toxicities were infectious complications (n = 61) and gastrointestinal tract mucositis (n = 31). One patient of 76 died due to treatment-related complications. The multivariate analysis revealed the following risk factors: therapy response (hazard ratio (HR) 2.2; p

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method to treat malignancy and some solid tumors which may be accompanied by life-threatening immune and infectious complications refractory to standard immunosuppressive and antibacterial therapy. According to literature data, fecal microbiota transplantation (FMT) may be applied to restore functional activity of microbiota and to overcome antibiotic resistance. Two clinical cases of FMT in critical ill patients who had developed acute graft-versus-host disease (aGvHD) of intestine after allo-HSCT are presented in the article. The aim of the study was to assess FMT efficiency and safety in immunocompromised critically ill patients. Results. Following FMT, a complete regress of aGvHD signs as well as reduction of systemic infectious process were registered, due to probable modulation of the immune response. In one patient, elimination from respiratory ways of carbapenemase-producing Klebsiella pneumoniae positive for NDM- and OXA-48- producing was noted, like as elimination of Pseudomonas aeruginosa synthesizing KRS-type carbapenemase. Conclusions. FMT may be considered an alternative approach to intestinal aGvHD treatment in critically ill patients after allo-HSCT.

In the retrospective multicenter study during 2007–2017 we included 59 oncohematological patients with mucormycosis and 541 patients with invasive aspergillosis. Our study showed that mucomorhycosis more often developed in children and adolescents (p = 0.001), and after «graft versus host» disease development (p = 0.0001). Patients with mucormycosis were more immunosuppressed: severe neutropenia was in 88 % vs. 82 %, median duration of neutropenia ‒ 30 days vs. 14 days, p = 0.0001, lymphocytopenia – 77 % vs. 65 %, median duration of lymphocytopenia – 25 days vs. 14 days, p = 0.001. The main sites of infection were lungs, nevertheless in patients with mucormycosis it was less frequent (73 % vs. 97 %, p = 0.02), but more frequent were ≥2 organs involvement (42 % vs. 8 %, p = 0.001) and paranasal sinuses involvement (15 % vs. 6 %, p = 0.04). Typical clinical features of mucomorhycosis were localized pain syndrome (53 % vs. 5 %, p = 0.0001), hemoptysis (32 % vs. 6 %, p = 0.001), on lung computed tomography scan – pleural effusion (53 % vs. 7 %, p = 0.003), lesions with destruction (38 % vs. 8 %, p = 0.0001) and “a reverse halo” symptom (17 % vs. 3 %). The overall 12-week survival was significantly lower in patients with mucormycosis (49 % vs. 81 %, p = 0.0001). In both groups unfavorable prognosis factors were: ≥2 organs involvement (p = 0.0009) and concomitant bacterial or viral infection (p = 0.001 and p = 0.008 respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (p = 0.006), in invasive aspergillosis patients – early bronchoscopy (p = 0.003), voriconazole use (p = 0.0007) and secondary antifungal prophylaxis (p = 0.0001).

Introduction. The question of the most adequate treatment strategy of AML in cases when it is impossible to perform allogeneic HSCT because of any reason still remains open.The aim of this study was to assess the long-term survival of patients with AML who received chemotherapy (CT) or autologous HSCT as consolidation in the first remission of the disease. It was included 135 patients aged 18 to 67 years, with a verified diagnosis of AML (except FAB M3) in the study. Of these, 100 patients received only CT, 35 patients received consolidation with autologous bone marrow transplantation. Patients who achieved remission after completion of induction CT courses received one of three treatment options as consolidation: 1) chemotherapy of standard-intensity (sCT), 2) high-dose chemotherapy (HDCT), 3) autologous HSCT (autoHSCT) conducted after 1–2 courses of high-dose CT. Adverse prognostic factors were identified as: age over 40 years, hyperleucocytosis more than 50,0 × 10 9/L and unfavorable cytogenetic and molecular-biological risk group.Materials and methods. Depending on the number of prognostic factors at the onset of disease relapse-free survival (RFS) was 47 % in their absence, 45 % in the presence of 1 factor, in the presence of 2 factors – 14 % (p = 0,000), regardless of the variant of consolidation therapy (sCT, HDCT, autoHSCT). A high level of white blood cells adversely affects OS (38 % vs. 22 %) and increases the frequency of relapse (52 % vs. 69 %) when performing only CT (sCT and HDCT). At initial white blood cells level more than 50,0 × 10 9/L the 5-year OS was 60 % when performing both autoHSCT and HDCT. Performance of autoHSCT at failure to achieve remission after the 1st induction course CT is associated with the best 2-year OS (62 % vs. 35 %, p = 0,05), EFS (50 % vs. 22 %, p = 0,05) and RFS (50 % vs. 37 %, p = 0,05) in comparison with HDCT and sCT. In favorable cytogenetic risk group 5-year RFS was 80 % when performing autoHSCT and 67 % when performing HDCT; the 5-year OS was 80 % regardless of consolidation therapy option.Conclusion. AutoHSCT is the preferred consolidation option in favorable risk group patients, and after failure to achieve remission after the 1st CT course.

Introduction. Steroid-refractory graft-versus-host disease (srGVHD) is one of the most severe and life-threatening complications of allogeneic hematopoietic stem cell transplantation. Currently, there is no standard treatment for this complication. In addition, there is no data on the pharmacoeconomics of various methods in the Russian Federation. The objective is to compare the effectiveness and cost of treatment of acute and chronic srGVHD, as well as the use of different approaches in therapy. Material and methods. We have conducted a pilot study in 12 srGVHD patients treated with ruxolitinib and in 24 patients of wellmatched historical control, who treated with etanercept for the acute srGVHD and with extracorporeal photopheresis for chronic srGVHD. Results. The 6-month therapy of acute GVHD was associated with significantly higher cost than therapy of chronic GVHD (4.138±2.672 vs 1.862±1.122 thd. rub., р=0.004). The major factors driving up the costs were bacterial infections (р=0.022), opportunistic viral infections (р

Objective. Data analysis of the register of patients with invasive aspergillosis (IA), which was founded in Saint Petersburg (1998–2017), and clinical case description of successful treatment of IA and mucormycosis with lungs involvement in a patient with Hodgkin’s lymphoma.Materials and methods. In the study were included 29 oncohematological patients with IA and mucormycosis. In control group were included 483 oncohematological patients with IA. We used criteria EORTS/MSG, 2008 for IA and mucormycosis diagnosis.Results. We identified that the combination of IA and mucormycosis significantly often develops in patients with acute lymphoblastic leukemia (32 %, р = 0.001), and allogeneic hematopoietic stem cells transplants (allo-HSCT) recipients (52 %, р = 0.001). In mixed-infection Aspergillus nidulans was frequent IA etiological agent (11 %, р = 0.001). The main mucormycosis etiological agents were Rhizopus spp. (45 %), Lichtheimia corуmbifera (20 %). The main sites of the localization were lungs (76 %), disseminated process and paranasal sinuses involvement were identified more frequently (45 % and 17 % (р = 0.0001; р = 0.002), respectively). Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24 %, р = 0.008), radiological signs – lesions with cavities destruction (38 %), hydrothorax (29 %) and a “reverse halo” symptom (17 %). Antifungal therapy received 76 % of patients, surgery – 34 %.Conclusion. Mucormycosis was revealed in 5.7 % of patients with IA. The main risk factors for co-infection are allo-HSCT, long-term agranulocytosis, lymphocytopenia and glucocorticosteroid therapy. Overall 12 weeks survival in patients with mixed-infection was 38 %, significantly lower than in patients with IA (р = 0.005). An unfavorable prognosis factor was dissemination of mycotic infection (р = 0.009).

Based on the annual UNAIDS reports the number of HIVinfected patients is continually growing since 1983. Antiretroviral Therapy (ART) allows to prolong life expectancy, but the problem of life quality and overall survival is still remaining. Nowadays, in the era of ART, one of the main cause of mortality in HIV-infected patients is malignancies. Lymphomas play one of the key roles in this group of diseases. The treatment of lymphomas includes combined regiments of chemotherapy with a curative potential. High dose chemotherapy with autologous hematopoietic stem cell transplant (auto-HSCT) is the main path of the treatment for relapsed / refractory lymphomas. In the last few years with a development of the genome editing technology auto-HSCT is becoming one of the most promising methods of HIV treatment. The case of “Berlin patient” when allogeneic HSCT from donor with mutation CCR5-delta32 lead to cure from HIV and proof of concept the efficacy of the gene therapy for HIV based on HSCT. Hematopoietic stem cell transplantation with edited autologous HSC (CCR5 knockout by site-specific genome editing tools with engineering nucleases) is a comprehensive treatment for this cohort of patients. On one hand, high dose chemotherapy with auto-HSCT cures the malignancy; on the other hand auto-HSCT works as a delivery method for the edited cells and creates an environment for the HIV eradication. This review is dedicated to HIV and oncology, methods of treatment of hematological malignancies and HIV-infection using genome editing technology based on HSCT.

Relevance. Hematopoietic stem cell transplantation (HSCT) is one of methods to care patients with malignancy, hematologic and hereditary diseases; in most cases, it requires prolonged and massive substitutionary transfusion therapy. Analysis of effectiveness, cost and need for blood components in different types of HSCT would allow blood transfusion department for more accurate planning in blood output.Objective – to determine the need for blood components in different types of HSCT.Material and methods. From December 2000 to December 2015, 851 patients with malignancies, hematologic and hereditary diseases who underwent 915 HSCT (54repeatedly) were included into the study.Results. Substitutionary transfusion therapy was required in 849 HSCT (92.8% of cases Red blood cell-containing blood components were used in 842 HSCT (92%), platelet containing – in 795 HSCT (86.8%), fresh frozen plasma – in 228 HSCT (24.9%). The total number of blood transfusion in 1 case of autologous HSCT was 14.7 doses, in allogeneic HSCT – 18.5 (p=0,01). On average, transfusion therapy for one recipient of autologous HSCT cost – 57 817.4 RUB, for recipient of allogeneic HSCT – 181 710.3 RUB. The need for blood components was increased in the presence of progression/relapse of the underlying disease (p=0.0001), allogeneic HSCT compared to autologous HSCT (p=0.0001), in patients with a long history of transfusion (more than 30 blood transfusions).Conclusion. Substitutionary transfusion therapy is a key factor increasing the effectiveness of treatment with the help of HSCT by prevention and treatment of anemic syndrome and hemorrhagic complications. Allogeneic HSCT compared to autologous HSCT was associated with significantly higher financial expenditure for providing substitutionary transfusion therapy.

Reduction of minimal residual disease to undetectable levels is the key criterion for efficiency of allogeneic hematopoietic stem cell transplantation (alloHSCT), along with engraftment of transplanted cells with complete replacement of recipient hematopoiesis, i. e., full posttransplant chimerism. Among different approaches, molecular genetic techniques are preferable, being based on the analysis of highly polymorphic DNA sequences (short tandem repeats, STRs). However, this approach, despite its high specificity, has a limited sensitivity. In this regard, it seems appropriate to introduce more sensitive diagnostic solutions, in particular, analysis of insertion/deletion (InDel) polymorphisms, followed by real-time detection of PCR products. The data obtained upon analysis of several genetic markers have shown higher sensitivity of this method. However, the deviations in the range of 10 to 90 % in evaluation of the cell ratios indicates the feasibility of using this approach just to evaluate the residual populations of recipient cells.

The aim of the research is to identify factors influencing the safety and efficacy of the transfusion therapy with hematopoietic stem cell transplantation (HSCT). From January 1 to December 31, 2015, 329 patients with hematologic diseases and malignancies who had undergone 367 HSCT were included into the study. Transfusion therapy was conducted in 345 HSCT – 94 % of cases. Totally, 9074 cases of transfusion of blood components were recorded: red blood cellcontaining – 2378 (26.2 %), plateletcontaining – 6255 (68.9 %), fresh frozen plasma – 441 (4.9 %). АВ0incompatibility between the donor and recipient was determined in 60.4 % of cases (n=154) in HSCT from allogeneic donor. Acute «graft versus host disease» was observed in 34.9 % of cases (n=89). Hemorrhagic complications were in 46 cases (12.5 %), mainly nasal, gastrointestinal bleeding and hemorrhagic cystitis. Pprevention and treatment of anemic and hemorrhagic complications in HSCT requires longterm and massive transfusion therapy with the availability of АВ0-incompatibility. The use of leukofiltrated, γ - or x-ray irradiated, individually and immunologically compatible blood components can reduce the risk of development of acute and delayed transfusion reactions in HSCT.

In prospective multicenter study were included 20 pediatriconcohematologic patients with mucormycosis. Age: 3 – 17 yy (median – 11), females – 60%. The diagnosiswas made according to EORTC/MSG 2008 criteria (post mortem – 25%). The main underlying disease was acutel eukemia (70%), risk factors – prolong severe neutropenia (median – 31 d) and lymphocytopenia (median – 33 d) after cytostatic chemotherapy or hematopoietic stem cells transplantation. Etiology agents were Lichtheimia corуmbifera, Rhizopus spp. and Rhizomucor spp. Main sites of infection were lungs (65%) and paranasal synuses (30%), dissemination – 45%. Antifungal therapy (amphotericin B lipid coplex, posaconazole, caspofungin, amphotericin B) was used in 75% patients, surgery – 30%. Overall mortality in 12 weeks was 70%.

Primary myelofibrosis (PMF) is а chronic BCRABL–negative myeloproliferative disorder with progressive clinical course. Allogeneic stem cell transplantation is the only treatment optionin patients with PMF with curative potential. Most of PMF patients have active disease phase at the moment of alloHSCT. The Januskinase inhibitor ruxolitinib is effective in decreasingof tumor mass before alloHSCT. Here we report our experience in administration of ruxolitinib as pre and posttransplant therapy of patients with PMF as well as patients with polycythemia vera and essential thrombocythaemia with transformation into myelofibrosis.

Refractory chronic graft-versus-host disease (cGVHD) is the complication of allogeneic hematopoietic stem cell transplantation (HCT) that signi ficantly impacts quality of life, may be associated with morbidity and mortality and has limited treatment options. 16 adult pts (median age 22, range 16 - 51 y.o.) with refractory cGVHD were enrolled. 6 pts were on steroids upon inclusion. 11 patients had severe (NIH) cGVHD, 6 - moderate, and have received 1-3 anti-cGVHD treatments before IL-2. Pts received IL-2 sc injections 1 MIU 3 times a week. Median duration of treatment was 2.5 moths (range 1 - 8 months). Partial clinical response was observed in 5 pts, complete response in 2 pts with overall response of 44 %. There was an improvement of Karnofsky in 25 % of pts, reduction in NIH severity scores in 37.5 % of and any objective response also in 44 % of pts. With median follow-up of 14 months overall survival was 62.5 %, non-relapse mortality was 12.5 % (2 pts), 25 % of patients had a relapse of underlying disease.

Pathogenesis of acute leukemia is associated with the presence of genetic and functional aberrations in hematopoietic stem cells. However, as one of the possible factors contributing to the progression of disease could be regarded as the pull of the stromal cells of bone marrow. In this paper we evaluated the major functional characteristics of stromal cells: proliferative activity, hematopoiesis supportive and differentiation ability, as well as analysis of the expression of adhesion molecules. Stromal cells derived from acute leukemia patients in comparison with healthy donors are characterized by a high proliferative activity and a pronounced ability to osteogenic and adipogenic differentiation with prominent expression of hematopoietic stem cells homing mediating molecules.

The aim of the study was to compare the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) and chemotherapy (CT) of acute myeloid leukemia (AML) in first remission (CR1), to identify factors influencing the results. We compare the efficacy alloHSCT in CR1 (n = 70) and CT (n = 52). Patients were stratified by age, the level of leucocytes, the origin of AML, cytogenetic risk group and response to induction CT. Five-years overall and disease-free survival (OS and DFS) were higher in the group alloHSCT (67 and 65 % vs 46 and 30 % (p = 0.02 and p = 0.001)). Benefits of DFS after alloHSCT was in standard and high-risk cytogenetic groups (78 % versus 29 % (p = 0.001), and 34 % vs 17 % (p = 0.007)). The risk of relapse (RR) was 24 % in patients after alloHSCT vs. 57 % for CT (p = 0.003). Comparing the RR after alloHSCT and CT depending on the cytogenetic risk groups: standard (HR0.2(CI95 %0.07 - 0.56) p = 0.002), and high (HR0.27(CI95 %0.08-0.86) p = 0.03). Additional factors affect the RR were the origin of AML (de novo) (HR0.47 (CI95 %0.3-0.74) p = 0.001), the hyperleukocytosis (HR1.91 (CI95 %1.09 - 3.32) p = 0.02), and no remission after the first course CT (HR3.32(CI95 %1.57-7.0) p = 0.002). The efficacy of alloHSCT compared with CT is higher both in standard and high-risk cytogenetic group.

The article focuses on aspects of T. gondii reactivation/reinfection in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). We have observed 297 patients who received conditioning therapy and allogeneic grafts due to different oncohematological or lymphoproliferative diseases (1 to 60 years old, at a mediane of 19 years). Conditioning regimens were either myeloablative (35%), or non-myeloablative (65%). DNA diagnostics of T. gondii was performed on a regular basis at 0 to 6 months post-HSCT. IgG and IgM antibodies against T. gondii were determined in 78 patients before HSCT, as well as in their donors. T. gondii DNA post-transplant proved to be positive in 13% of blood specimens, 9% of cerebrospinal liquor samples, 11% of bronchoalveolar cell lavages, and in 5% of urine sediments. In adolescent patients (10 to 14 years old), an increased prevalence of T. gondii was found in patients who received myeloablative treatment (p = 0.01). When assessing posttransplant dynamics of T. gondii, we have revealed distinct increase in the pathogen excretion within 1st month after HSCT (p = 0.03). Finally, initial presence of IgG antibodies against T. gondii in the patients was associated with lower incidence of the pathogen reactivation post-transplant.

HLA matching of the donor / recipient pair is a major factor associated with the outcome of allogeneic stem cell transplantation. In the presentstudy we analyzed the risk of severe acute graft-versus-host disease, graft failure, 2.year overall survival of the patients after allogeneic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair.

155 children and adolescents who had been diagnosed oncohematological diseases and had undergone allogeneic hemapoetic stem cell transplantation were examined. In post-transplant period 80% of patients developed different bacterial complications. Main risk factors of bacterial infections were acute leukemia (73%), acute «graft versus host disease» (61%), severe infectious complications before HSCT (30%), cytomegaloviral reactivation (51%). Main causative agents were Kl. pneumoniae (15%), Escherichia coli (8%), Enterobacter sp. (7%), Pseudomonas sp. (6,5%), Enterococcus sp. (16,5%), S.еpidermidis (13,5%). Most frequent involved sites are urinary tract (30,6%), lungs (22,5%) and bacteriemia (38,7%). Rise in ciprofloxacin resistans among Entorobactri, aerobic and Gram-positive cocci. General survival rate of patients with bacterial complications was 36,3% (p

Invasive aspergillosis – is severe mycotic infection that often occurs in hematological patients and is characterized by high mortality. We examined the immunological parameters of hematological patients with invasive aspergillosis developed after cytostatic chemotherapy. Was founded, disruption of all parts of the immune respons: reduction in the absolute number of T-helper cells (CD4 +), natural killer cells (CD16 +), lowering of IFN-γ and IL-10 production, reduction in the number of B-lymphocytes and immunoglobulin levels of all classes, suppression killer ability of neutrophils are features of immune status in hematological patients with invasive aspergillosis receiving cytostatic chemotherapy.

Traditionally, the concern of fatal complication is a major obstacle to transfer patients with unfavorable course of Hodgkin’s lymphoma tonational transplantation centers. Early mortality after high-dose chemotherapy with autologous hematopoietic stem cell transplantation(HSCT) in the Russia, Ukraine and Belarus was assessed in this retrospective multicenter study.Patients and methods. The study included 372 patients with unfavorable course of Hodgkin’s lymphoma received HSCT between 01.1990and 06.2013: 35.5 % patients with primary resistance, 30.6 % with early relapse, 33.1 % with late relapse and 0.8 % during consolidation offirst complete remission.Results. During first 100 days after HSCT died 14 (3.8 %) patients, during first year – 31 (8.4 %) patients. During the study period a significant decrease in the 100-day and 1-year mortality rate was observed (p < 0.0001 for both). Among patients received HSCT in 1990–1995, 1996–2000, 2001–2005 and 2006–2013 the 100-day mortality was 19.4 %, 6.3 %, 1.1 % and 0.6 %, respectively. 1-year mortality for the same intervals was 32.3 %, 14.7 %, 4.5 % and 1.9 %, respectively.Conclusions. Currently HSCT in patients with unfavorable course of Hodgkin's lymphoma in national transplant centers, accompanied by an extremely low risk of fatal toxicity.

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.

Extracorporeal photopheresis (ECP) has been used as a component of combined immunosuppressive therapy in 53 patients with steroid-refractoryacute “graft-versus-host” disease. Overall response was observed in 35 patients (66 %; 95 % CI 52.6–77.3): complete response (CR) in 15 pts (28.3 %; 95 % CI 18–41.6) and partial response (PR) in 20 pts (37.7 %; 95 % CI 25.9–51.2). 3-year OS was 39 % in patients with clinical response (CR or PR); in the absence of clinical response OS was 8 % during the first year (p < 0.0001). Median methylprednisolone dose before ECP was 2 mg/kg/day, and at the end of ECP course – 0.7 mg/kg/day (p < 0.0001).

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.

Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L). Eighteen patients with bronchial asthma (BA), and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden). Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03), , and in cases of chronic GvHD (p < 0.03), and in a sub-group with lymphoproliferative disorders (р = 0.007) as compared to the group of non-hematological diseases.Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03), as well in GvHD compared with lymphoproliferative disorders (р < 0.05).A direct correlation was found between serum ECP levels and absolute eosinophil counts in peripheral blood for general hematological group (r = 0.51; р = 0.000001), and for a group of patients with lymphoproliferative diseases (r = 0.9; р = 0.000001). Hence, a quantitative determination of soluble eosinophylic proteins and mast cell-specific enzymes in blood serum are useful for diagnostics and monitoring of various hypereosinophilic conditions in oncohematological disorders. (Med. Immunol., vol. 10, N 4-5, pp 361-370).

Research objective: To assess the impact of AB0 erythrocyte antigens system incompatibility on complications incidence after allogeneic hematopoietic stem cell transplantation (alloHSCT). Patients and methods. The study included 240 patients - recipients for alloHSCT with oncological and hematological diseases. The median age was 19.0 (1-66) years. The research revealed that overall incidence of acute graft-versus-host disease (aGVHD) was higher in the case of AB0-incompatibiIity (p

Aim. To study the incidence and risk factors of bacterial infections and the efficiency of empirical antibacterial therapy in patients in the early period after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Subjects and methods. The study included 155 patients who had undergone allo-HSCT. Myeloablative conditioning was used in 39% of the patients. All the patients with neutropenia (NP) received antibiotic prophylaxis with fluoroquinolones until recovery of white blood cell counts or before systemic antibiotic therapy. Antibiotic therapy and a change of antibiotics were considered effective in achieving persistent apyrexia and positive clinical changes. Results. The incidence of febrile neutropenia (FNP) in the patients after allo-HSCT was 63%. The duration of grade 4 leukopenia did not depend on the conditioning regimen. Neutropenic fever was noted in 68% of the patients with NP lasting longer 10 days. In shorter-duration NP, the rate of fever was 52%. Among the patients with mucositis, the frequency of FNP episodes was significantly higher (69% versus 52%; p=0.02). The diverse spectrum of isolated bacteria was represented as gram-positive cocci in 45% of cases; Klebsiella pneumoniae and Enterobacter cloacae were more common among gram-negative ones (24%). The efficiency of empirical antibiotic therapy was 57% (25% for monotherapy, 53% for combined treatment regimens); the early mortality was 2%. Conclusion. Infection-related FNP is noted in 68% of the patients in the early posttransplantation period and the risk factors of its development are NP duration, oral colonization with pathogens, and the absence of invasive mycosis after allo-HSCT. Antibacterial prophylaxis significantly decreases the incidence of bacterial complications. Empirical monotherapy with third- or fourth-generation cephalosporins and carbapenems against infections in a transplantation patient is as effective as their combination with aminoglycosides.

Aim. To evaluate the efficacy of antithymocyte globulin (ATG) used in conditioning modes before allogeneic hemopoietic cell transplantation (allo-HCT) and its effect in reducing the incidence of posttransplantation complications. Subjects and methods. The study assessed the results of 92 allo-HCTs depending on the presence or absence of ATG in conditioning modes, the doses of Atgam (60 mg/kg or more), the presence or absence of acute leukemia (AL) in remission before HCT. Results. In patients with AL in remission receiving ATG in conditioning modes (Atgam 60 mg/kg or thymoglobulin 7.5 mg/kg), overall three-year survival was 60%. Increasing the dose of Atgam up to more than 60 mg/kg resulted in higher transplantation-associated mortality (TAM) rates than did with the Atgam dose of 60 mg/kg (p < 0.01). Conclusion. Allo-HCT is the treatment of choice for patients with AL in the presence of an HLA-identical related or unrelated donor. The use of Atgam in a course dose of not more than 60 mg/kg or thymoglobulin 7.5 mg/kg in conditioning modes is associated with low TAM rates and higher overall survival in earlier-stage disease in complete clinical hematological remission as compared with those in patients with expanded-stage AL, rather than in AL in remission at the start of conditioning before HCT.

Aim. To evaluate the efficiency of related and unrelated allogeneic bone marrow transplantation (allo-BMT) versus immunosuppressive therapy (IST) in patients with aplastic anemia (AA) having no HLA-compatible bone marrow donor. Subjects and methods. The study covered 61 patients (34 men and 27 women) diagnosed as having acquired AA. Of them, 51 patients were diagnosed as having severe AA, 5 had supersevere AA, and 5 had non-severe AA. Combined IST (antithymocyte globulin (ATG) + cyclosporin A (CsA)) was used in 43 patients; allo-BMT was performed in 18. The basic types of ATG (ATGAM (Pfizer), thymoglobulin (Genzim), ATG (Fresenius), and goat antilymphocyte globulin (ALG) (Research Institute of Gerontology, Ministry of Health of the Russian Federation) were administered. CsA was given in a dose of 5 mg/kg/day. The standard conditioning regimen (ATGAM + cyclophosphanum) and fludarabine-containing (fludarabine + cyclophosphanum + ATG; busulfan + fludarabine + ATG) programs were used in the allo-BMT group. A combination of CsA and metothrexate was given to prevent a graft-versus-host reaction. Results. Among the IST-receiving patients, overall survival (OS) was 71%. After the first course of IST by follow-up month 6, the response rate was 74%. The second course of IST was performed in 7 patients unresponsive after the first-line IST and in 8 patients with recurrent AA. After the second course of IST, the response rate was 46.7%. Four patients who failed to achieve remission after 2 courses of IST received its third course. A complete response was obtained in 3 patients. In 18 patients following allo-BMT (related and unrelated), OS was 86%; event-free survival was 65. In 12 patients after related allo-BMT, OS was 91.7%. Conclusion. Related allo-BMT is the method of choice if there is a HLA-compatible sibling. If there are contraindications to it or no related donor, IST with ATG + CsA is indicated. Ineffective IST is an indication for unrelated allo-BMT that may be recommended as life-saving therapy for young patients under 40 years of age.

Antithymocyte immunoglobulins remain to be one of the most effective immunosuppressants used in transplantology and in the treatment of autoimmune diseases. The unique features of the mechanisms of individual antithymocyte globulin preparations should be borne in mind. Due to its polyclonal nature, thymoglobulin provides a wide spectrum of diverse immunomodulatory effects, which is the basis for its wide use in order to reduce the risk for graft rejection and a graft-versus-host reaction and to treat aplastic anemia.