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Introduction. Sinusoidal obstructive syndrome (SOS)/veno-occlusive liver disease (VOD) is one of the most dangerous complication of allogeneic hematopoietic stem cell transplantation (alloHSCT).The objective of our study was to analyze risk factors associated with SOS/VOD in children and adults after alloHSCT.Methods and materials. The study included 76 patients who were diagnosed with the development of SOS/VOD after alloHSCT performed in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation between 2001 and 2019. 25 patients (32.9 %) were younger than 18 years, 51 patients (68.1 %) — 18 years and older. Among them, 17 patients were treated with defibrotide at a dose of 25 mg/kg per day, median therapy duration — 21 day.Results. One-year overall survival (OS) was significantly higher when partial and complete response to the therapy was achieved — 45 %, than when there was no response — 0 % in the general group (p = 0.001). According to the results of multivariate analysis of unrelated alloHSCT HR 2.040 (95 %CI 1.112-3.744, р = 0.021), acute GVHD HR 0.496 (95 % CI 0.272-0.903, р = 0.022), moderate/severe SOS/VOD HR 2.423 (95 % CI 1.298-4.524, p = 0.005) statistically significantly influenced the 1-year OS. Defibrotide and accompanying therapy did not significantly influence the 1-year OS in children and adults (n=76) - 53 % and 54 % (p=0.86), respectively. In a multivariate analysis. unrelated alloHSCT HR 8.172 (95 %CI 2.176-30.696, р=0.002) and moderate and severe SOS/VOD HR 9.077 (95 % CI 2.425-33.978, р=0.001) significantly influenced the 1-year OS in the pediatric group.Conclusion. The understanding of risk factors of adverse prognosis in patients SOS/VOD facilitates selection of patients who will benefit the most from therapy with defibrotide. Early administration of defibrotide in the course of VOD/SOS is crucial to achieve response.

Malassezia spp.is a commensal yeast that represents normal microflora in humans and some animals. However,Malassezia spp.can cause life-threatening invasive mycosis. Evidence on Malassezia spp. infections is limited mostly to a case reports describing disease in newborns and premature infants, because lipid infusions (total parenteral nutrition) given through central venous catheter is a major risk factor. Here, we report two cases of CNS infection caused by Malassezia species in non-neonates with acute leukemia.

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/m 2 . 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.

The aim of the research. Evaluation of the structure of viral hepatitis in patients with oncohaematological diseases and activity of ALT and AST during various methods of treatment of the main disease.Materials and methods. Retrospective analysis of data from 2000 patients treated during 2001–2014 in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation Pavlov of the First Saint Petersburg State Medical University was carried out. The dynamics of cytolytic enzymes during therapy (polychemotherapy, transplantation of hematopoietic stem cells, symptomatic) of oncohematological diseases was evaluated between the patients with concomitant chronic viral hepatitis (N=175) and without liver pathology (N=203). Analysis was performed with SAS software. Results. Over a 10-year follow-up period, 9% of the oncohematological patients of the specialized center identified markers of hemocontact viral hepatitis. The results of the study showed that in patients with concomitant viral hepatitis, in contrast to a group without hepatitis the activity of ALT and AST significantly increased compared to baseline values after the treatment of hematological malignancy. It was twofold increase of the activity of enzymes after transplantation of hematopoietic stem cells and 3–4- fold incease after courses of polychemotherapy. In patients without viral hepatitis, changes in enzyme activity after such therapy were not observed. Summary. Thus, the associated effect of concomitant viral hepatitis and toxic effects of treatment methods with the use of polychemotherapy and transplantation of hematopoietic stem cells was proven on the development of cytolytic syndrome in oncohematological patients.

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

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.

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).

Introduction. AB0-incompatibility in different types of allogeneic hematopoietic stem cell transplantation (HSCT) may be an additional aggravating factor for the development of immunological complications and decrease treatment efficacy. Materials and methods. From May 1999 to December 2015 in R.M. Gorbacheva Memorial Research Institute for Children Oncology, Hematology and Transplantation 1131 patients with malignancies and hereditary diseases were included to the study, which were performed 1428 allogeneic HSCT: allogeneic unrelated – 814 (57.0 %), allogeneic related – 344 (24.1 %), haploidentical – 267 (18.7 %), umbilical cord blood in 3 patients (0.2 %). Age was 0–76 years, median – 25 years. Results. In 54.6 % of cases (n = 780) АВ0-incompatibility was determined: major – 37.8 % (n = 295); minor – 45.4 % (n = 354); combined – 16.8 % (n = 131). АВ0-incompatibility in allogeneic HSCT did not influence overall survival (p = 0.56), frequency of acute graftversus-host disease (GVHD) (p = 0.2). There was an increased frequency of acute GVHD in combination with reduced intensity conditioning regimens and АВ0-incompatibility (30.8 %) compared with myeloablative regimens (15.3 %; p = 0.002). Conclusion. The presence of АВ0-incompatibility is not a limiting factor to perform allogeneic HSCT, however, it demands high quality prophylaxis and sophisticated transfusion therapy to prevent immune complications.

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.

It is well-known that stromal cells have a crucial role in the regulation of hematopoiesis and engraftment [1]. Stromal cell studies became even more attractive after the c-kit ligand (stem cell factor) was discovered [2,3]. Data dealing with the biological properties of stromal cells in malignant hematological disorders are still scarce, however. The aim of this study is to evaluate the influence of bone marrow fibroblastand stormal cell-conditioned medium (CM of patients with acute leukemia (AL) on the proliferation and differentiation of normal and leukemic cells with respect to the development of potential diagnostic and prognostic markers.

Multiple myeloma (MM) is a malignant clonal B-lymphoproliferative disease. Survival ranges from a few months to many years [7]. The determination of prognosis for the disease’s course is important in therapeutic choice. At least two factors determine the course of MM: 1) the biology of myeloma cells and 2) the interrelation of malignant cells and host organism.