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The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis treatments. In this study we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with median age of 30 (range, 18–55) years, who previously underwent allo-HSCT were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values ​​of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT and were used to model relapse risk with several machine learning approaches. GBM proved superior to the other algorithms utilized and provided maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment and chronic GvHD had the highest value in the model. It was shown that after Day + 100 both error rates don’t exceed 22%, while before D + 100 the model fails to make accurate prediction. After day + 100 patients with chronic GVHD, BCR::ABL1 level more than 0.11% post-transplant and current BCR::ABL1 above 0.06% can be classified as high risk group of relapse. At the same time, if the patient had no chronic GVHD after allo-HSCT till the prediction moment, he should be classified to a high risk group already with a BCR::ABL1 level more than 0,05% at any time point. GBM model with posttransplant laboratory values of BCR::ABL1 provides high prediction of relapse in the era of TKIs prophylaxis. Validation of this approach is warranted.

Objectives Therapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure. Methods This study retrospectively analyzed 21 patients with r/r cHL who were treated with the combination of Nivo + BV after Nivo failure. The response was evaluated by PET–CT scan according to the LYRIC criteria. Adverse events (AEs) were assessed according to NCI CTCAE v.4.03. Results Median follow-up was 19 (9–47) months. The ORR was 57%. The median OS was not reached, 24 month OS was 80% (95% CI 50–93%). Median PFS was 12 months with 24 month PFS of 31% (95% CI 12–53%). Any grade AEs were observed in 12 patients (63%), 3–4 grade AEs in 2 patients (10%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after Nivo + BV was performed in 8 (38%) patients. The median time between Nivo + BV and allo-HSCT was 8 (5–21) months. Conclusions Combination of Nivo + BV in r/r cHL after nivolumab monotherapy failure is potentially an effective and safe approach. Supplementary Information The online version contains supplementary material available at 10.1007/s10147-021-02085-6.

Allogeneic hematopoietic stem-cell transplantation (HSCT) remains the only curative option for patients with advanced chronic myeloid leukemia (CML). However, outcome is dismal and of short follow-up. The objective of the study was to determine long-term outcome and risk factors in patients with a history of CML Blast Crisis (BC; n = 96) or accelerated phase (n = 51) transplanted between 1990 and 2018. At transplant, patients had a median age of 39 (range 7–76) years and were in ≥CP2 (n = 70), in AP (n = 40) or in BC (n = 37) with a diagnosis-HSCT interval of median 1.9 (range 0.3–24.4) years. Overall survival (OS) amounted 34% (95% CI 22–46) and progression-free survival (PFS) 26% (95% CI 16-36) at 15 years. Adverse risk factors for OS and PFS were low CD34+ count in the graft, donor age (>36 years) and BC. Cumulative incidence of Non-Relapse Mortality (NRM) was 28% (95% CI 18–38) and of relapse (RI) 43% (95% CI 33–53) at 15 years. PB-HSCT and HSCT after 2008 were favorable prognostic factors for NRM, while family donor and patient age >39 years were independently associated with higher RI. HSCT resulted in long-term OS in patients with advanced CML. OS was improved in non-BC patients, with donors ≤36 years and with higher CD34+ dose in the graft.

In recent years, the important role of disturbances in the intestinal microbiota and its possible correction in children with oncological and autoimmune diseases has been established. The aim of the article is to review the literature data on the issue and to describe own experience of fecal microbiota transplantation (FMT) in children with an intestinal form of acute graftversus-host disease (GVHD). Materials and methods of research: a prospective single-center study included 7 patients aged 3 to 10 years with gut GVHD developed after transplantation of allogeneic hematopoietic stem cells (allo-HSCT). The clinical effects of FMT have been studied in children using rating scales during 120 days after this procedure. Time-dependent changes in the composition of fecal microbiota were assessed by the method of multiplex polymerase chain reaction test-system (PCR). Results: the literature data show a significant role of the content and ratio of of the main bacterial classes of Firmicutes and Bacteroides in the development of the immune response in cancer and autoimmune processes, as well as the possibility of correcting disorders using FMT. The first-hand experience of FMT in children with gut GVHD and antibiotic-resistant colitis is presented. Complete or partial response to GVHD therapy after 120 days was achieved in 6 (86%) patients in the absence of serious adverse events after FMT. From day +3 after FMT, increased amounts of B. fragilis gr., F. prausnitzii and E. coli were registered in fecal microbiota (p

Immune checkpoint inhibitors (ICI) have demonstrated high therapeutic efficacy in relapsed or refractory classical Hodgkin lymphoma (r/r cHL). Nevertheless, despite the accumulated data, the question of the ICI therapy duration and efficacy of nivolumab retreatment remains unresolved. In this retrospective study, in a cohort of 23 adult patients with r/r cHL who discontinued nivolumab in complete response (CR), the possibility of durable remission achievement (2-year PFS was 55.1%) was demonstrated. Retreatment with nivolumab has demonstrated efficacy with high overall response rate (ORR) and CR (67% and 33.3% respectively). At the final analysis, all patients were alive with median PFS of 16.5 months. Grade 3-4 adverse events (AEs) were reported in 36% of patients, and there was no deterioration in terms of nivolumab retreatment-associated complications.

Leukemia-associated myelitis is a rare but underestimated complication. It has a different etiology associated with both, the main disease and its treatment methods. It requires differential diagnosis with funicular myelosis, polyradiculoneuropathy, tumor and hemorrhagic formation, stroke, dysmetabolic manifestations, as well as with the consequences of treatment of the underlying disease using radiation, cytostatic, targeted therapy.It should also be differentiated from paraneoplastic myelopathy and progression of the underlying disease. However,with the help of neuroimaging methods, it can be detected more recently than a detailed clinical picture appears. A case report of myelopathy in a 31 year old patient with acute lymphoblastic leukemia is presented. Treatment of the underlying disease was carried out with the use of chemotherapy, radiation therapy, allogeneic hematopoietic stem cell transplantation and targeted therapy. The nature of the disease,i.e. recurrent course of acute lymphoblastic leukemia, the variety of treatment methods, and the absence of focal changes in neuroimaging in the zone that determines clinical manifestations, made it necessary to consider a wide range of possible etiological factors for the development of myelopathy. Myelopathy was confirmed by MRI 2.5 months after the debut of neurological symptoms, which corresponds to modern concepts and time criteria for visualization in neurooncology. The article presents the criteria for diagnosing myelopathy, a complication of acute lymphoblastic leukemia. It should also be differentiated from However, with the help of neuroimaging methods, it can be detected more recently than a detailed clinical picture appears.

Aim. To comparatively analyze myelofibrosis treatment outcomes with the use of ruxolitinib versus ruxolitinib with subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) as well as to assess the efficacy of ruxolitinib in pre- and post-transplantation periods. Materials & Methods. The study enrolled 78 myelofibrosis patients who were referred to the RM Gorbacheva Scientific Research Institute to determine the indications for allo-HSCT. Allo-HSCT was performed in 33 patients, among them 32 patients with ruxolitinib pre-conditioning (ruxolitinib + allo-HSCT group). They received reduced intensity conditioning (fludarabine 180 mg/m2 and busulfan 10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included cyclophosphamide 50 mg/kg on Day +3 and Day +4, ruxolitinib 10 mg per day from Day +5 to Day +100 (n = 31), rabbit antithymocyte globulin, tacrolimus, and mycophenolate mofetil (n = 2). Ruxolitinib without allo-HSCT was administered to 45 patients (ruxolitinib group). Between the groups there were no significant differences with respect to gender, age, diagnosis, and molecular genetic variant. Results. Median therapy duration in ruxolitinib group was 16 months (range 2-78 months). In 2 (4 %) patients partial response was achieved, 8 (20 %) patients showed clinical improvement, in 16 (39 %) patients stable disease (SD) was reported, in 15 (37 %) patients disease progression (DP) was detected. The treatment succeeded in reducing the spleen size in 8 (20 %) patients and in relieving disease symptoms in 16 (39 %) patients. Cumulative incidence of progression within 3 years was 44 % (95% confidence interval [95% CI] 27-60 %). In ruxolitinib + allo-HSCT group median ruxolitinib therapy duration was 7 months (range 3-22 months). As a result, clinical improvement in 9 (28 %) cases, SD in 17 cases (53 %), and DP in 6 (19 %) cases were observed. In 5 (20 %) patients acute GVHD of grade 2-4, in 3 (12 %) patients acute GVHD of grade 3-4, and in 6 (24 %) patients chronic medium severity GVHD were identified. Within 1 year nonrelapse mortality was 28 % (95% CI 14-44 %). The 3-year cumulative incidence of relapse was 12 % (95% CI 3-28 %) in ruxolitinib + allo-HSCT group. According to the landmark analysis performed throughout 6 months from the first visit to the center, the 3-year overall survival in the group with allo-HSCT was 80 %, whereas in ruxolitinib group it was 41 % (p = 0.022), 12-month landmark analysis resulted in 77 % and 43 % (p = 0.028), and 18-month landmark analysis showed 86 % and 46 % (p = 0.015) in two groups, respectively. Conclusion. Despite the efficacy of JAK1/2 inhibitor ruxolitinib, the risk of myelofibrosis progression is not to be underestimated. Therefore, in DIPSS intermediate-2 and high-risk patients the issue about performing allo-HSCT should be promptly clarified.

The article presents the results of a study of the prevalence of acute (exacerbation of chronic) otorhinolaryngological pathology at the stages of hematopoietic stem cell transplantation (HSCT). The frequency of the studied pathology was assessed at the stage of pre-transplant screening, at the stage before graft engraftment and at the stage after graft engraftment up to 180 days. The study included 1129 cases of HSCT performed at the Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation from January 2017 to December 2019. The median age of the patients was 27 years (min – 0,36, max – 73,22). Allogeneic HSCT was performed in 784 (69,4%) cases, autologous HSCT in 345 (30,6%) cases. The power of the study was 0,95. A comparative analysis using the Pearson χ2 criterion revealed that infectious complications were significantly more frequent with allo-HSCT than with auto-HSCT, both at the stage before engraftment (χ2 = 21.8 at p

The article presents the results of studying the features of the endoscopic picture of acute rhinosinusitis in patients with anemia and neutropenia, who underwent hematopoietic stem cell transplantation (HSCT). The questions of the influence of the level of hemoglobin on the presence of hyperemia of the mucous membrane of the nasal cavity, as well as the influence of the level of neutrophils on the presence of pus in the exudate in rhinosinusitis, are being studied. The study was carried out based on the Clinic of the Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology, and Transplantation. The study included 49 episodes of rhinosinusitis in HSCT recipients diagnosed in the period from day –7 to day +30 after transplantation. The control group included 46 patients with rhinosinusitis undergoing treatment at the otorhinolaryngology clinic. In the course of the study, the influence of the level of neutrophils on the presence of purulent discharge in rhinosinusitis was established. The threshold value, below which the chances of having pus in the exudate significantly decreased, was 2.6 x 109/l (sensitivity and specificity of the method – 81.6 and 76.1%, respectively). It was also found that hemoglobin level affects the presence of hyperemia of the nasal mucosa. It was shown that at a hemoglobin level less than 119 g/l, the odds of presence of hyperemia of the nasal mucosa significantly decreased (sensitivity 77.6%, specificity 95.5%). Thus, in patients with anemia and neutropenia, one should remember the likelihood of the absence of pus and hyperemia of the nasal mucosa in the presence of rhinosinusitis. These criteria should not be the main ones in such a group of patients, and the diagnosis should be based on the results of an X-ray examination and the presence of other symptoms.

Introduction: There is growing evidence of a connection between tumor clonal profile and its clinical impact. However, there is a lack of a feasible and reliable method for clonal profiling in actual clinical practice. Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder characterized by morphological dysplasia, cytopenia and a high risk of evolution to acute myeloid leukemia. The clinical outcome of myelodysplastic syndrome is greatly heterogeneous; therefore, specific examination of clonal profiles is needed to resolve the prognosis of patients with such complex disorders. Purpose: Development of a pipeline specifically for determining the clonal profiles in patients with myelodysplastic syndrome on the basis of target next-generation sequencing data. Results: The pipeline was developed and evaluated on a set of 35 patients with high-risk myelodysplastic syndrome. It is possible to use the target sequencing data in order to assess the heterogeneity of clonal profiles and characterize their genetic features. This approach allows you to identify the consistency between a specific individual profile and the disease prognosis, which can be critical for the treatment decision. Herein, the characterization and analysis of clonal profiles are presented. Practical relevance: The information about relation patterns between clonal profile characteristics (number of subclones, mutations-per-clone rate) and clinical outcome can be used by doctors in current practice for a more accurate therapy selection depending on the identified individual specificity of the disease.

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).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.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.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.Цель.Оценка клинической эффективности, спектра побочных эффектов и динамики микрофлоры после трансплантации фекальной микробиоты (ТФМ) у пациентов с кишечной формой реакции трансплантат против хозяина (РТПХ). Материалы и методы.Проспективное одноцентровое сравнительное исследование в НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой включало 27 пациентов с кишечной формой РТПХ после трансплантации аллогенных гемопоэтических стволовых клеток. ТФМ выполнена 19 пациентам, плацебо получали 8 человек. По оценочным шкалам изучены клинические эффекты и безопасность ТФМ у пациентов. Изменения состава фекальной микробиоты оценивали методом мультиплексной полимеразной цепной реакции. Результаты.После ТФМ по сравнению с группой плацебо выявлены статистически значимо более высокие средние значения общей бактериальной массы (р=0,00088),Bifidobacteriumspp. (р=0,021),Escherichia coli(р=0,049) иBacteroides fragilisgr. (р=0,000043). При этом изменения в бактериальной массе наблюдались у пациентов с клиническим ответом (р=0,0057), а бактериальная масса у пациентов без полного ответа сопоставима с группой плацебо (р=0,31). Частичный ответ по тяжести РТПХ достигался быстрее в группе ТФМ, чем в группе плацебо (медиана 4 дня против 48 дней;р=0,014). Полный ответ наблюдался у 8 (42%), 14 (74%) и 16 (84%) больных через 30, 60 и 90 дней в группе ТФМ соответственно против 0%, 1 (13%) и 4 (50%) в группе принимавших плацебо. Частота и выраженность нежелательных явлений после ТФМ сопоставима с группой плацебо. Заключение.ТФМ у пациентов с резистентными формами кишечной РТПХ сопровождается позитивной динамикой клинических проявлений наряду с восстановлением кишечной микробиоты по ряду маркерных бактерий. Метод мультиплексной полимеразной цепной реакции можно использовать для оценки приживления фекального трансплантата. ТФМ пациентам с резистентной формой кишечной РТПХ не сопровождается жизнеугрожающими побочными эффектами. Однако требуются дополнительные исследования для уточнения клинической эффективности ТФМ.

Summary Fecal microbiota transplantation (FMT), as any other medical procedure, requires standardization of results, approaches, monitoring of its dynamics and microbiota engraftment evaluation. The aim of the present study was to compare efficiency and results of PCR and 16S RNA-based sequencing in order to trace the dynamics of microbiota composition after FMT. Patients and methods The prospective, single-center study included 27 patients with acute intestinal and chronic (overlap syndrome) graft-versus-host disease (GvHD) developed after allogeneic hematopoietic stem cell transplantation (HSCT). FMT in 19 cases was performed, mostly, with ingestible capsules, eight placebo-treated patients were included into control group. Quantitative changes of different bacterial groups in fecal microbiota were assessed by means of real-time multiplex PCR, being compared with16S rRNA sequencing technique at the terms of D+3, D+16, D+30, D+60 and D+120 following FMT. Clinical response was determined by 4 scales evaluating intestinal syndrome and GvHD grade. Results When evaluating stool consistence according to Bristol scale as an index of GvHD therapy efficiency, we have observed complete clinical response by the D+120 after FMT in nine cases (47% with Bristol score of ≤4 points), and nine patients (47%) showed improved stool properties (>4 points). In the placebo group, complete or partial response was revealed, respectively, in one (13%), and four cases (50%) on the D+120. Multiplex PCR of fecal microbiota has shown a different time course in FMT- and placebo-treated patients, when compared to their initial (pre-FMT) levels. Total bacterial mass and copy numbers of distinct microbial species exhibited sufficient increase after FMT. Such shifts were demonstrable on D+30 for total microbial mass (p=0.002); Escherichia coli (p=0.001); Bacteroides fragilis group (p=0.05); Faecalibacterium prausnitzii (p=0.005). Meanwhile, the numbers Lactobacillus spp., and Bacteroides thetaiotaomicron, generally, were not changed over this time period. Moreover, in the control group (placebo) we have not found significant fecal microbiota changes against initial levels during 120 days monitoring period. Over 120 days of observation, we have also found some differences of the microbiota dynamics for the subgroups with complete response and partial/no response: Bifidobacterium spp. (р

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.Моноклональная гаммапатия ренального значения (МГРЗ) представляет собой новую нозологическую группу в современной нефрологии и онкогематологии. Под МГРЗ понимают поражение почек, обусловленное действием нефротоксичного моноклонального иммуноглобулина, продуцируемого клоном В-клеточной линии, который не достигает критериев, необходимых для начала противоопухолевой терапии по онкогематологическим показаниям. Результатом воздействия моноклонального белка на почечную паренхиму является неуклонное прогрессирование дисфункции почек вплоть до утраты функции органа, что в соответствии с единой позицией международного консенсуса гематологов и нефрологов определенно указывает на необходимость клон-ориентированного лечения МГРЗ, несмотря на отсутствие критериальных онкогематологических показаний. Основной проблемой МГРЗ в Российской Федерации является недоступность для большинства пациентов своевременной диагностики и лечения данной патологии, что обусловлено, во-первых, недостаточной осведомленностью гематологов и нефрологов страны в отношении МГРЗ, во-вторых, отсутствием в большинстве медицинских учреждений необходимых диагностических ресурсов, в-третьих, отсутствием утвержденных рекомендаций и медико-экономических стандартов лечения этой болезни. Текст настоящего консенсуса заключает в себе мнение специалистов РФ в отношении нозологической классификации, диагностики и подходов к терапии МГРЗ и основан на итогах проведенного совместного совещания ведущих гематологов и нефрологов страны. Совещание состоялось 1516 марта 2019 г. в рамках симпозиума Плазмоклеточные дискразии и лимфопролиферативные заболевания: новые подходы к терапии, проведенного в ФГБОУ ВО Первый СПбГМУ им. акад. И.П. Павлова. Настоящий консенсус гематологов и нефрологов призван наметить основные практические пути решения проблемы МГРЗ в РФ, которые кратко сформулированы в виде заключительных положений.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III–IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57–89%) in acute GVHD and 81% (95% CI 67–92%) in chronic. Overall survival was 59% (95% CI 49–74%) in acute group and 85% (95% CI 70–93%). The major risk factors for lower survival were grade III–IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III–IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

Randomized multicenter trials in the area of hematopoietic stem cell transplantation (HSCT) face considerable challenges, therefore, their amount is relatively small. Most clinical guidelines are based on the data of multicenter registry studies or well-controlled prospective single-center non-randomized studies. To determine the criteria of a well-controlled single-center trial the results of which can be confi rmed by a multicenter analysis, the total of 44 groups of patients from 22 cooperative studies in collaboration with EBMT were analyzed. The results of these studies were compared with single-center data and the results of the planned studies of RM Gorbacheva Scientifi c Research Institute of Pediatric Oncology, Hematology and Transplantation. In 43 % of cases signifi cant diff erences were observed. The probability of diff erences did not decrease with an increasing number of patients in the single-center groups, but became higher (odds ratio 1.037; 95% confi dence interval 1.001-1.074; p = 0.046), which highlights the diff erences in methods of single- and multicenter trials. While analyzing the reasons for signifi cant diff erences the following necessary criteria for high-quali ty single-center trials in the area of HSCT were formulated: 1) conditioning regimens and graft-versus-host disease prophylaxis (if they are not subject of the study) need to be consistent with the most frequently used practices; 2) groups of patients should be status-homogeneous; 3) the trial must not include patients treated more than 5 years before the analysis; 4) patients should receive current antitumor therapy at pre- and post-transplantation stages; 5) each compared group should include more than 30-40 patients

Aim. To assess prognostic factors and to analyze the outcomes of nivolumab therapy in patients with relapsed/re-fractory classic Hodgkin's lymphoma (cHL) after autologous hematopoietic stem cell transplantation (auto-HSCT). Materials & Methods. The retrospective analysis included 42 patients treated with nivolumab 3 mg/kg after auto-HSCT in the period from 2016 to 2020. The response to nivolumab therapy was assessed every three months by whole-body PET/CT based on LYRIC criteria. Toxicity profile was assessed by establishing adverse events (AE) based on NCI CTCAE 4.03 criteria. Results. The study included 42 patients with relapsed/re-fractory cHL: 21 (50 %) men and 21 (50 %) women. The median age was 32.5 years (range 22-43 years). At diagnosis the following cHL stages were identified: stage II in 14 pts (33.3 %), stage III in 12 pts (28.6 %), and stage IV in 16 pts (38.1 %). Primary chemoresistance after the first-line therapy was observed in 26 pts (61.9 %) and early relapse in 4 pts (9.52 %). The median follow-up was 38 months, 3-year overall survival was 97 % (95% confidence interval, 95% CI, 83.2-99.6 %), 3-year progression-free survival (PFS) was 34.8 % (95% CI 20.3-49.9 %; median 12.9 months). Objective response was reported in 69 % of patients, complete response (CR) in 33.3 %, partial response in 35.7 %, stable disease in 7.1 %, indeterminate response in 14.3 %, and progression in 9.5 % of patients. The analysis of factors affecting PFS revealed significant differences in patients who reached CR after 6 nivolumab cycles: 3-year PFS 56.2 % (95% CI 24.4-79.1 %) vs. 25.2 % (95% CI 10.46-43.1 %) in patients who did not reach CR (p = 0.054). If extranodal lesions were identified at nivolumab therapy onset, PFS was 29 % (95% CI 7.8-37.5 %) vs. 68 % (95% CI 35.9-86.8 %) in their absence (p = 0.0079). The overall rate of AEs on nivolumab therapy was 92.9 %, severe AEs of grade 3-4 were observed in 19.1 % of patients. Conclusion. Nivolumab shows high efficacy in the treatment of patients with relapsed/refractory cHL after the failure of auto-HSCT and considerably improves prognosis compared with historical control. The efficacy of nivolumab is independent of brentuximab vedotin use and duration of prior therapy. Throughout the follow-up period the toxicity level of nivolumab was acceptable and controlled. Clinical factors that affect prognosis for patients on immunotherapy were identified.

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 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. 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 St-Petersburg State Medical University, St-Petersburg, Russia. 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 predictive value of graft composition and plasma biomarkers on the outcome of allogeneic HSCT is well known for conventional GVHD prophylaxis based on calcineurin inhibitors with or without antithymocyte globulin. Currently, there is limited data whether these results could be translated to post transplantation cyclophosphamide (PTCy). The prospective extension cohort of NCT02294552 trial enrolled 79 adult patients with acute leukemia in CR. Twenty-six received matched-related bone marrow (BM) grafts with single-agent PTCy and 53 received unrelated peripheral blood stem cell graft (PBSC) with PTCy, tacrolimus, and MMF. The grafts were studied by the flow cytometry, and plasma samples were analyzed by ELISA. In the cluster and major component analysis, we determined that transplantation from donors with high content of CD3, NKT, and CD16-CD56 + subpopulations in the PBSC grafts was associated with poor immunological recovery and compromised event-free survival (50% vs. 80%, HR 2.93, p = 0.015) both due to increased relapse incidence and non-relapse mortality. The significant independent predictor of moderate and severe chronic GVHD was the high prevalence of and iNKT, Vβ11, and double-positive cells in the PBSC grafts from young donors (HR 2.75, p = 0.0483). No patterns could be identified for BM grafts and for plasma biomarkers.

Invasive fungal disease due to Candida spp. – Invasive candidiasis/candidaemia, is a life-threatening complication in immunosuppressed patients. The publications on epidemiology of invasive candidiasis (IC) in children after hematopoietic stem cell transplantation (HSCT) is limited. The purpose of the study was to study the epidemiology of IC in children after HSCT for the 7 years in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation. In 2009–2016 yy have been performed 754 HSCT in children: 494 allogeneic and 260 autologous. The study was approved by the Independent Ethics Committee of the Raisa Gorbacheva Memorial Research Institute of Children's Oncology, Hematology and Transplantation. A retrospective study included 22 cases of invasive candidiasis in after HSCT. EORTC/MSG 2008 criteria were used for the diagnosis of proven invasive candidiasis as well as to evaluate response to therapy. Incidence of IC was 2.9%: allo-HSCT – 3% (n = 15), auto-HSCT – 2,7% (n = 7). The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The etiology: Candida parapsilosis – 50%, Candida albicans – 27%, Candida krusei – 14%, Candida tropicalis – 5%, Candida dubliniensis – 4%. The most frequent underlying diseases was acute leukemia – 45% (n = 10). The median age was 8 y.o. (3 month–18 years). The median day of onset of IC after allo-HSCT was 63 days (4–243), auto-HSCT – 12 days (3–20). Febrile fever was the main clinical symptom; septic syndrome develops in 32% cases. Antifungal therapy was with echinocandins – 23%, lipid ampho B – 27%, triazole (fluconazole, voriconazole) – 32%, without therapy (due to early mortality) – 18%. Overall survival (OS) at 30 days from diagnosis invasive candidiasis was 50%. The central venous catheter (CVC) removal was the only factor significantly improved OS (70% vs 33%, p = 0,035). Incidence of Invasive candidiasis in children after hematopoietic stem cell transplantation was 2.9%. The main etiology agent was Candida parapsilosis. Invasive candidiasis infections most often affect leukemia patients, after allo-HSCT developed later than auto-HSCT. Overall survival at 30 days from the diagnosis was 50%. Removing of CVC improved overall survival in children with invasive candida infections after HSCT