In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4-0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010-2014 vs. 38% in 2015-2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23-0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin's disease (HR 0.1, 95% CI 0.1-0.3), multiple myeloma (HR 0.4, 95% CI 0.2-0.7) and solid tumors (HR 0.2, 95% CI 0.2-0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1-0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1-0.5), Hodgkin's disease (HR 0.1, 95% CI 0.0-0.4), non-Hodgkin's lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0-0.6), inborn diseases (HR 0.2, 95% CI 0.2-0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2-0.8).

In healthy persons, lung microbiota shows close correlations with microbial landscape of upper respiratory tract.However, pronounced changes of lung microbiota are revealed by analysis of bronchoalveolar lavage (BAL) in severe pneumonias and other pulmonary complications, expecially, in immunocompromised patients.E.g., following intensive cytostatic therapy and hematopoietic stem cell transplantation (HSCT), severe impairement of lung microbiota is observed, due to transient cytopenia, immunocompromised state and massive antibiotic prophylaxis.BAL microbiology shows a number of commensal bacteria including potential pathogens from other infectious sites.Hence, the aim of our study was to evaluate the diversity of aerobic and facultative anaerobic microorganisms in BAL samples from the HSCT patients.

Objective. To study the features of invasive aspergillosis (IA) due to A. non-fumigatus versus A. fumigatus in adult (≥ 18 years) recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2016-2021. Materials and methods. The study included 33 patients with IA caused by A. non-fumigatus (n = 20) and A. fumigatus (n = 13). A comparative analysis of cases of IA, the results of therapy and outcomes in patients after allo-HSCT in the RM Gorbacheva Research Institute was performed. Diagnostic criteria EORTC / MSGERC 2020 were used. Results. Invasive aspergillosis caused by A. non-fumigatus made up the majority (60.6 %) of IA cases with an identified pathogen registered in patients after allo-HSCT in the period from 2016 to 2021. The main etiological agents in the A. non-fumigatus group were A. niger in 13 (65 %) patients, A. flavus – in 4 (20 %). The median day of diagnosis of A. non-fumigatus IAwas + 110 days (17–2093), for A. fumigatus it was + 46 days (2–866) (p = 0.171). Overall 12-week survival was 55 % and 59.2 % in the A. non-fumigatus and A. fumigatus groups, respectively (p = 0.617). The majority of patients in both the A. fumigatus (n = 10, 77 %) and A. non-fumigatus (n = 16, 80 %) groups received voriconazole as initial antifungal therapy. Second-linetherapy was required in 2 (10 %) patients with A. non-fumigatus IA: liposomal amphotericin B and echinocandins with or with-out posaconazole, and 2 (15 %) patients in the A. fumigatus group: liposomal amphotericin B and voriconazole in combination with echinocandins. A comparative analysis showed that in patients from the two groups, none of the assessed signs (gender, age, underlying disease, disease status at the time of transplantation, time from diagnosis to allo-HSCT, source of hematopoietic stem cells, conditioning regimen, donor type, antifungal prophylaxis, cytomegalovirus reactivation, severe acute and chronic graft-versus-host disease) did not differ significantly. Conclusions. A. niger is the main causative agent of IA caused by A. non-fumigatus. Patients characteristics, their treatment and outcomes did not differ significantly between the A. non-fumigatus and A. fumigatus groups.

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(р<0,001).The development of early PC in remission of the underlying disease significantly affected OS (p=0.001).The probability of PC development is 2.26 times higher in patients older than 9 years (p=0.006). When comparing the intensity of conditioning regimens (MACvsRIC) in remission of the underlying disease, we did not get significant differences in the incidence of PC (p>0.05). 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.

Bronchiolitis obliterans (BO) is a severe form of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Aim. The aim of current study was to evaluate the incidence, risk factors, and clinical manifestation of BO after allo-HSCT. Methods. The study included 1189 adult patients who received allo-HSCT at R.M.Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Academician I.P.Pavlov First Federal Saint-Petersburg State Medical University, Healthcare Ministry of Russia in 2008 – 2019. BO was diagnosed according to the US National Institutes of Health criteria (2014), including pulmonary function test (PFT) and high-resolution computed tomography (HRCT) of the chest. We analyzed the cumulative incidence of BO with competing events, risk factors in the Fine – Gray regression model, clinical symptoms, BO severity, and bronchial obstruction formation dynamics. Results. BO was diagnosed in 42 (3.5%) patients. Cumulative incidence of BO was 1.8% (95% CI, 1.2 – 2.7), 3.9 (95% CI, 2.8 – 5.2) и 4.5% (95% CI, 3.2 – 6.1) at 1, 3, and 5 years after allo-HSCT, respectively. The median time of BO onset and diagnosis was 321 (86 – 1 771) and 371 (161 – 2 134) days, respectively. Risk factors were HLAmismatched unrelated and haploidentical donor (ОР – 2.301, 95% CI, 1.247 – 4.246; p = 0.0076), myeloablative conditioning (ОР – 2.544, 95% CI, 1.384 – 4.674; p = 0.0026) and GVHD prophylaxis without posttransplant cyclophosphamide (ОР – 2.152, 95% CI, 1.154 – 4.013; p = 0.0160). The clinical manifestation included cough (88 %) and shortness of breath (90%). Bronchial wall thickening (95%) and expiratory air trapping (79%) were frequent chest HRCT findings. Mild, moderate, and severe BO was identified in 9 (21%), 12 (29%), and 21 (50%) patients, respectively. The median forced expiratory volume in 1 second (FEV1 ) was 39% (20 – 74). The most significant loss of bronchial conductivity was between day + 100 and 1 year after allo-HSCT. Conclusion. The large cohort study provided details on current incidence, risk factors, and clinical features of BO after HSCT. The results create the basis for predicting and early diagnosis of BO after allo-HSCT

Objective. To study risk factors, etiology, clinical signs and treatment outcomes of invasive aspergillosis (IA) and mucormycosis combination (IAM) in children. Materials and Methods. A retrospective review of Saint-Petersburg register (1998–2021) of patients with IA was done and children with IAM were included. EORTC/MSGERG 2019 criteria were used for diagnosing and treatment results evaluation of invasive mycosis. We presented a clinical case of IAM in a child with acute lymphoblastic leukemia relapse. Results. A total of 12 children with IAM were included. They accounted 8% of all pediatric patients with invasive aspergillosis (n = 152). IAM was diagnosed in children with hematological malignancies and solid tumors from 4 to 16 years (median age – 11.5 years), mostly in girls (83%). Main risk factors of IAM were prolonged lymphopenia (75%, median 22 days) and neutropenia (67%, median 30 days) due to chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. The predominant etiological agents of IA were Aspergillus niger (33%), A. nidulans (33%) and A. fumigatus (17%), of mucormycosis – Lichtheimia corymbifera (50%) and Rhizomucor spp. (50%). Based on EORTC/MSGERG 2019 criteria, «proven» mucormycosis was diagnosed in 83% of patients, «probable» – in 17%. «Probable» IA was found in 100% of patients. The most common clinical sites of IAM were the lungs (75%) and paranasal sinuses (43%), multifocal involvement was revealed in 33% of patients. Mucormycosis developed during antifungal therapy of IA in 83% of patients. Antifungal therapy of mucormycosis received 75% of patients (amphotericin B lipid complex – 89%, posaconazole – 78%, caspofungin – 33%), combined antifungal therapy – 33%, surgery – 50%; combination of surgical and antifungal treatment was used in 42% of patients. The overall 12-week survival was 77.8%. The use of combined surgical and antifungal treatment significantly improved the survival of children with IAM (p = 0.023). Conclusions. Mucormycosis was diagnosed in 8% of children with IA. IAM developed mostly in patients with hematological malignancies (83%), prolonged lymphopenia (75%) and neutropenia (67%) against the background of chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. In 83% of patients mucormycosis was diagnosed during antifungal therapy for IA. The development of IAM increased overall 12-week mortality (50%). The combination of antifungal therapy with surgical treatment significantly improved prognosis of IAM (p = 0.023).

Introduction: Bronchiolitis obliterans syndrome (BOS) is an extremely unfavorable chronic GVHD manifestation with limited therapeutic options. Recent small retrospective series and the only prospective randomized trial have demonstrated different response rates (8.6 - 66.7%) in patients with BOS to JAK1/2 inhibitor ruxolitinib (Streiler C. et al. BMT 2020, Zhao Y. et al. Front. Pharmacol. 2021, Zeiser R. et al. NEJM 2021). Here we report a single-center study of the ruxolitinib efficacy for BOS in adults after HSCT.

Background. Invasive aspergillosis (IA) is dominant among invasive fungal infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The emergence of new immunosuppressive drugs, the expanding use of antifungal agents with activity against Aspergillus spp. on the one hand, and the improvement of the diagnostics and therapy on the other hand affect epidemiology of IA.

Efficiency of hematopoietic stem cell transplantation and accompanying therapy in the patients with hereditary and malignant diseases of blood system depends, e.g., on timely and sufficient treatment and rehabilitation programs.At all stages of the therapy performed, key role belongs to medical nurses.Therefore, education and training of highly skilled and motivated nursing staff is required, due to implementation of new specialty "medical nurse for rehabilitation" in Russia since 2020, arrangement of rehabilitation departments and centers with multidisciplinary medical teams (MRHT).