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Study objective: to evaluate frequency of CMV, HHV-6, and EBV reactivation in children within 60 days after HSCT.Materials and methods: The study was carried out in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation of the Pavlov First Saint Petersburg State Medical University We analyzed 95 medical records of pediatric patients who underwent HSCT in 2021. Pretransplant serostatus for CMV, EBV, HHV-6 was studied, as well as the frequency and timing of virus reactivation after transplantation. In the prospective part, 35 children aged from 1 to 17 years were enrolled. The pretransplant evaluation included detection of anti-CMV, anti-HHV-6, and anti-EBV IgM and IgG by ELISA, and blood PCR for viremia. DNA of herpes viruses was identified by quantitative blood PCR on the day of HSCT, and then 10, 20, 30 and 60 days after HSCT. The number of viral DNA copies was calculated per 105 cells. Statistical analysis was carried out using SPSS Statistics 22 software package.Results: On pre-transplant evaluation, 47 of 95 pediatric patients were tested for CMV with positive result in 36 children, 27 patients were tested for EBV and 17 were positive. HHV-6 DNA was detected in 3 of 25 patientsMostly, reactivation of herpes viruses occurred in the early period up to 60 days. HHV-6 reactivation was observed on average 25±4 days after transplantation, significantly earlier than for CMV and EBV.In a prospective study, reactivation of CMV, HHV-6, and EBV was revealed in 28 (80%) patients within 60 days of transplantation, with a maximum number of patients in 20 days after HSCT.A trend toward an increase in CMV and HHV-6 concentration in blood was observed on days 10 and 20 after HSCT, with a maximum viral load of HHV-6 and minimal EBV replicative activity. Clinically significant manifestations of herpesvirus infection were diagnosed in 19 (54.3%) patients.Conclusion: High seropositivity for CMV and EBV was revealed in children before transplantation. Herpes viruses reactivation occurs early in post-transplant period, on the 20th day after HSCT, HHV-6 in forms of mono- and mixed infection predominates with a trend toward increasing viral load.

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.

Relevance. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) makes it possible to treat severe malignant and non-malignant hematopoietic disorders system. Pulmonary complications (PC) occur in 40–60 % of patients after allo-HSCT. However to date, the effect of HSCT on functional and morphological pulmonary changes in recipients remains insufficiently studied.The objective of current study was to evaluate risk factors affecting long-term survival in children and adolescents after allo-HSCT.Methods and materials. The current study was both retrospective and prospective. The analysis included 362 patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), aged 5 months to 18 years, who received allo-HSCT at Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation in 2000–2018. All the patients underwent chest computed tomography (CT). When detecting CT changes, we performed fibrobronchoscopy (FBS) with microbiological examination of bronchoalveolar lavage (BAL).Results. PC were diagnosed in 124 patients (64 %) who received allo-HSCT in 2014–2018. Decrease of overall survival (OS) is associated with PC development during the first year after allo-HSCT(р0.05). Graft source, donor type, HLA-compatibility, recipient gender did not affect the incidence of PC (p>0.05). When using graft-versus-host disease (GVHD) prophylaxis (ptCYvsATG), the 5-year OS in patients without PC was 78.8 % and 62.8 %respectively. The 5-year OS in patients with PC was 51.8 % and 42.4 % respectively (р=0.007). Decrease of OS in patients with PC is associated with chGVHD(58.3 %,) (р=0.03).Conclusion. Pulmonary complications (infectious and non-infectious) in allo-HSCT recipients are more likely to occur in the first year after transplantation. Among bacterial pathogens, the predominance of Gr(-) flora remains. The incidence of pulmonary complications was significantly lower when using ptCY as a prevention of GVHD.

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.

Aim.Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD). Materials and methods.The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR. Results.After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group. Conclusion.FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

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.

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.

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).

The success of treatment of acute leukemia in children isdetermined by the biological type of the disdorder, the volumeof the tumor mass, extramedullary manifestations and toxiccomplications resulting from chemotherapy. Analysis of riskfactors, clinical data and neuroimaging may help to clarify thecause of the pathology of the central nervous system and to selectthe optimal method of treatment.

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.

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.

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.

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.

Risk factors of CMV replication in early period after allo-HSCT (D0‑D100) were – myeloablative conditioning – HR 3.74 (1.67–8.37), р = 0.001; unrelated donor – HR 2.18 (0.86–5.26), р = 0.10; HLA-matched donor – HR 0.24 (0.05–1.06), р = 0,06. In late posttransplant period (from D+100) significant risk factors of CMV-reactivation were (according to multivariate analysis) myeloablative conditioning – HR 13.17 (3.00–57.86), р = 0.001; combination of pretransplant remission of leukemia and using cyclosporine and methotrexate – HR 0.13 (0.03–0.50), р = 0.003; combination of aGVHD and CMV reactivation in early posttransplant period – HR 2.71 (0.86–8.50), р = 0.088; using of bone marrow – HR 0.37 (0.12–1.19), р = 0.095. We revealed the significant association of aGVHD and CMV-reactivation –OR 2.91 (1.07–7.92), р=0.006, and increased rate of cGVHD in patients with CMV replication at third month after allo-HSCT OR – 2.29 (1.03–5.08), р = 0.066. We revealed a tend to decreasing relapse risk in patients who had CMV-replication – HR 0.07 (0.004–1.17), р = 0.06. Cumulative incidence of CMV-disease was 28 %. CMV-disease was lethal in 44 % patients.

We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008). Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %), main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %), cytostatic chemotherapy (57 %), corticosteroid treatment (45 %), and allogeneic hematopoietic stem cells transplantation (29 %). The pathogens – A. fumigatus (42 %), A. niger (33 %), and A. flavus (21 %). The main site of infection were lungs (86 %). 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01), adequatetherapy with voriconazole (p = 0.002) and secondary antifungal prophylaxis (p = 0.0003) were positive prognostic factors for survival of patients with invasive aspergillosis.

Treatment results of allogeneic hematopoietic stem cells transplantation (allo-HSCT) with myeloablative (MAC) and reduced intensity (RIC) conditioning regimen in children and adolescents with unfavorable forms of acute lymphoblastic leukemia (ALL) were shown. One hundred and two ALL patients aged 1 to 21 years (mean – 12 years) who received allo-HSCT from 2000 to 2010 (31 patients with RIC and 71 patients with MAC) are included in the study. Analysis of overall and event-free survival in both groups showed comparable efficacy. The use of RIC as alternative conditioning regimen in children and adolescents with high risk ALL and poor general condition, comorbidities and infectious complications are discussed.

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).

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.