Objective of the study . Analysis of the treatment outcomes of patients with MLL rearrangements in the Republic of Belarus within protocols AML-MM-2000 and AML-MM-2006.

Materials and methods . The study included 151 patients with newly diagnosed acute myeloid leukemia (AML) who were treated according to protocol AML-MM-2000 and AML-MM-2006. 11q23 abnormalities were detected in 40 (26.5 %) out of 151 patients.

Results . The performed analysis of the survival outcomes of patients with 11q23 depending on the protocol showed that the probability of 5-year event-free survival (EFS) was significantly better (p = 0.0110) in children receiving treatment under protocol AML-MM-2006 (86 ± 13 %) compared with that of the patients included in protocol AML-MM-2000 (23 ± 12 %). Using protocol AML-MM-2006 allowed reducing the cumulative incidence of relapse (CIR) in this cohort from 46.2 ± 15.1 to 14.3 ± 14.3 % (p = 0.1609). EFS probability in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) was 100 %, whereas in the group without alloHSCT – 31 ± 12 %, p = 0.0359. The treatment outcomes of patients with t(1;11) are comparable to those with CBF leukemia. The risk of relapse in patients with t(10;11) is higher than in the rest of the 11q23 cohort (62.5 ± 19.2 % versus 21.9 ± 7.5 %; p = 0.0136). CIR in patients with t(9;11) decreased from 42.8 % in protocol AML-MM-2000 to 15.4 % in protocol AML-MM-2006 (p = 0.1411).

Conclusion . For the described cohort of patients alloHSCT is the best option for post-remission therapy. The worst prognosis is determined in patients with t(10;11), whereas the presence of t(1;11) is a favorable prognostic factor. Using the arm with cladribine showed to be effective in patients with t(9;11). To obtain reliable outcomes, we consider it reasonable to continue the study with the use of cladribine in patients with t(9;11).

Background . Using modern first-line chemotherapy more than 80 % of patients with classical Hodgkin’s lymphoma can be cured, however, in 15–20 % of cases there is a relapsed/refractory disease. The use of nivolumab in international clinical practice has significantly improved treatment results of patients with relapsed/refractory classical Hodgkin’s lymphoma.

Objective of this study is to evaluate the results of therapy with nivolumab in the сlinic of Pavlov First Saint Petersburg State Medical University.

Materials and methods . The retrospective analysis included treatment results of 101 patients with relapsed/refractory classical Hodgkin’s lymphoma who received nivolumab in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation from February 2016 to August 2018. The group included 90 patients who received nivolumab as part of an named patient program. Therapy response was assessed using CT/PET-CT in accordance with LYRIC criteria for response assessment of malignant lymphomas to immunotherapy. Safety and tolerability were assessed by registering adverse events in accordance with NCI CTCAE version 4.03 criteria. Results . Median follow-up was 25 months. The response was registered in 64 % of patients: in 32 (31.6 %) – complete response and in 33 (32.7 %) – partial response. Stabilization and progression as the best response were registered in 5 (4.9 %) and 10 (9.8 %) patients, respectively. Indeterminate response was observed in 21 (20.6 %) patients. The 2-year overall survival was 96 %; the median of overall survival was not achieved. Progression-free survival (PFS) in studied patients was 40.6 %. The median of PFS was 17.9 months. There were no significant differences in PFS between patients with a partial and indeterminate response. Adverse events were reported in 87.1 % of patients. Severe adverse events (III–IV grade) occur in 18.8 % of patients.

Conclusion . The results of a retrospective study of nivolumab therapy in Russian patients with relapsed/refractory classical Hodgkin’s lymphoma are consistent with published international data. Nivolumab demonstrates high efficacy as a monotherapy for relapsed/refractory classical Hodgkin’s lymphoma, regardless of previous therapy type and duration with well tolerance. Pseudo-progression phenomena during immunotherapy require revision of the traditional Hodgkin’s lymphoma therapy response criteria.

Immunotherapy is the most rapidly evolving field in clinical malignant hematology. Targeting of the B-lineage surface antigen CD19 in B-lineage acute lymphoblastic leukemia and B-cell lymphoma is a story of great success. Recently two approaches of CD19 immunotargeting were approved for clinical application: CD3 × CD19 bi-specific T-cell engager blinatumomab and CD19 chimeric antigen receptor (CAR) Tcells. Both approaches demonstrated an unprecedented activity in a cohort of patients with relapsed and refractory B-cell leukemia and lymphoma both in the adult and pediatric population. Early clinical research has showed that tumors are able to escape the immunological control and become resistant to the immune attack. Mechanisms of the tumor immune escape are being actively studied and include diverse pathways, such as alternative splicing of CD19 and immunosuppressive tumor microenvironment. Current review briefly summarizes data regarding the mechanisms of CD19-positive leukemia resistance to CD19 immune targeting and discusses potential approaches to overcome it.

Objective of the study was to compare blood clotting parameters in lymphoma patients with or without venous thrombosis (VT), as well as to analyze the duration and outcome of anticoagulant therapy in children, adolescents and young adults with lymphoma, whose program treatment was complicated by VT.

Materials and methods . The analysis included 28 patients with lymphoma (Hodgkin lymphoma – 5, non-Hodgkin lymphoma – 23), aged from 2 to 25 years (median – 16.0 years), whose program treatment in 2005–2017 was complicated by VT. The case-control study was carried out to compare the parameters of blood coagulation. The control group consisted of 22 patients, aged from 2 to 20 years (median – 15.5 years) with the same diagnosis, age, therapy protocol and phase of treatment who had no thrombotic complications. The comparison group consisted of 35 healthy children aged from 3 to 18 years (median – 14.0 years).

Results . There was no difference in majority of blood clotting parameters in lymphoma patients with or without VT. Hyperfibrinogenemia and an increased D-dimers level distinguished patients with lymphoma, regardless of the presence or absence of thrombosis, from healthy children of the same age (р <0.05). Anticoagulant therapy up to 3 months received 10 patients, for 4–6 months – 4, for 7–12 months – 12, up to 18 months – 2. One adult patient with a homozygous mutation 20210G>A gene of the factor II takes warfarin continuously for a long time after relapse of VT. Complete recanalization of the thrombosed vessel occurred within the first 3 months in 9 patients, within 4–6 months – in 1, within 7–12 months ‒ in 4. Partial recanalization within 3–12 months was confirmed in 8 patients. Vein obliteration, mainly the internal jugular vein, as the outcome of VT occurred in 6 patients within 4–12 months.

Conclusion . Detection of routine blood clotting parameters does not allow identifying patients with thrombosis among children, adolescents and young adults with lymphoma. Fibrinogen and D-dimers levels were significantly higher in lymphoma patients, than in healthy children. Anticoagulant therapy for 3–12 months led to the complete or partial recanalization of VT in 79 % of patients. To detect blood clotting parameters by thrombosis development, as well as to reveal and monitor transient and permanent risk factors are necessary to specify the cause of VT and to determine the appropriate anticoagulant therapy.

Background . The study of influence of residual tumor mass, determined by magnetic resonance imaging (MRI), on the progression-free survival (PFS) remains an actual problem. Since the visual assessment of tumor bone marrow lesion can be one of the criteria for the subsequent personalized treatment choice in multiple myeloma patients.

The objective of study was to determine the effect of bone marrow lesions detected by MRI after autologous hematopoietic stem cells transplantation (auto-HSCT) on PFS in multiple myeloma patients.

Materials and methods . The prospective study included 60 patients who underwent spine and pelvic bones MRI on the 100 th day after autoHSCT.

Results . Focal bone marrow changes were found in 47 of them – from 1 to 56 lesions (mean 6 ± 9). Significant (p = 0.01) differences of PFS in multiple myeloma patients depending on the presence or absence of tumor mass on 100 th day after auto-HSCT were revealed: with MRI negative status, 2-year PFS was 89 % versus 50 % in a group of patients with residual tumor mass.

Conclusion . MRI-negative status after auto-HSCT is a favorable prognostic factor contributing to prolonged disease-free survival.

The introduction of new monoclonal antibodies has become an integral part of the treatment of malignant tumors.

Brentuximab vedotin (Adcetris®) – anti-D30 monoclonal antibody conjugated with monomethyluristatin E – has become a new drug registered since February 2016 in the Russian Federation (SGN-35; Adcetris®). The Food and Drug Administration approved the Adcetris® since August 2011 as a therapy for refractory/recurrent Hodgkin’s lymphoma and anaplastic large cell lymphoma.

This article describes the clinical case of successful use of Brentuximab vedotin, accompanied by the development of a rare complication – tumor lysis syndrome – in an elderly patient with primary refractory ALK-negative anaplastic large cell lymphoma with massive eosinophilia.

Because of the successful implementation of modern treatment technologies at any stage of therapy of children with oncohematological diseases, their overall and disease-free survival has increased significantly. According to recent observations, 80 % of children after the completion of a special antitumor treatment continue to have changes of different organs. Almost all patients are at risk for late complications from the musculoskeletal system but little attention is paid to this issue. Evaluation of long-term complications from the musculoskeletal system and mineral metabolism in patients, development of their complex rehabilitation and prevention is an actual problem of pediatric oncology and hematology. This review summarizes data on long-term complications from the musculoskeletal system after special therapy. The necessity of diagnostics approaches harmonization and correction of not only the most common complications, but also little studied conditions, such as reduction of bone mineralization, is shown. It is noted that multidisciplinary rehabilitation treatment of children in remission can not only correct the consequences of the underlying disease, concomitant pathology and the consequences of special therapy but also reduce the disability of children.

Natural killer (NK) cells are the first population to recover after allogeneic hematopoietic stem cell transplantation. Since the report in 2002 by L. Rugerri et al. showing the effectiveness of NK cell alloreactivity in haploidentical stem cell transplantation, a lot of conflicting studies have appeared about the role of NK alloreactivity in haploidentical and matched unrelated donor transplantations. Current studies demonstrate that the beneficial effects of donor NK alloreactivity are dependent on the transplant protocol – conditioning regimen, graft processing procedure and graft-versus-host disease.

Background . Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal diseases of the hematopoiesis system characterized by dismyelopoiesis and cytopenia, the presence of cytogenetic aberrations and a high risk of transformation into acute myeloid leukemias. Diagnosis of MDS requires a comprehensive approach and mandatory performance of cytological, cytochemical and cytogenetic studies of bone marrow aspirate, as well as histological examination of trephine biopsy. However, in some cases it is necessary to undergo a diagnostic test that would allow verification of the MDS. The study of bone marrow aspirate by multicolor flow cytometry (MFC) can be considered as an additional diagnostic criterion in the diagnosis of MDS.

The objective of the study was to estimate the incidence of myelodysplastic features in patients with various forms of MDS by the MFC method. 

Materials and methods . The study included 79 patients with MDS: 8 with MDS with 5q deletion, 33 with MDS without excess blast cells and 38 with excess of blasts. A bone marrow aspirate test was performed by 6-color flow cytometry. The control group included 35 donors of allogeneic bone marrow. The analysis resulted in a conclusion on the Ogata score scale, the Wells prognostic scale and the combined Ogata–Wells scale. When using the screening method, the presence of two or more cytometric signs of MDS was detected in 60 (75.9 %) of 79 MDS patients. Wells score was higher in MDS group with an excess of blast than in others. Using the combined Ogata–Wells scale, cytometric aberrations were found in 70 (88.6 %) of 79 MDS patients. In patients with MDS with an excess of blasts, the incidence of increased CD34+ and/or CD117+ myeloid cells was higher than in MDS patients without an excess of blasts and an MDS with a 5q deletion. The frequency of abnormal cytometric parameters (anomalous expression of CD34, CD117, CD56+ myeloblasts) in these groups did not differ. In patients with isolated 5q deletion and MDS without excess of blasts, an increased proportion of CD7+CD34+ cells was more often detected than in MDS with an excess of blasts.

Conclusion . Thus, cytometric abnormalities in MDS are common, even in patients without excess of blasts. The MFC method can be used as an additional diagnostic method in the initial diagnosis of MDS.

Recently, interest in Investigator Initiated Trials (IIT)/Investigator Initiated Studies (IIS) in pharmaceuticals and medicine has increased.
The relevance of such trials is due, on the one hand, to increased knowledge of diseases pathogenesis, potential targets for drug exposure, and on the other, the development of technologies, primarily the Internet and computer methods that create opportunities for organizing collaboration, the collection and processing of information. Almost all participants in the process of creating new drugs and treatments – pharmaceutical companies, regulatory authorities, associations of doctors and patients – have realized the importance of supporting IIT and developed mechanisms for this.
The purpose of this article is to review new trends in IIT in the world and the possibilities for conducting them in Russia, and also exchange of experience in the development, approval and implementation of international IIT in our country.

The objective of the study was searching for surface antigen expression that could predict presence of translocation t(12;21)(p13;q22)/ETV6RUNX1 in pediatric B-cell precursor acute lymphoblastic leukemia patients.

Results . ETV6-RUNX1 fusion gene transcript was revealed in 118 (22.4 %) out of 526 children with B-cell precursor acute lymphoblastic leukemia. Leukemic blast cells in ETV6-RUNX1-positive patients more frequently had high CD10 expression, myeloid markers co-expression , including CD13, CD33, CD117, and absence of CD20 than in ETV6-RUNX1-negative ones. Nevertheless diagnostic test performance characteristics of each single parameter was not strong enough for predicting the presence of translocation t(12;21)(p13;q22)/ETV6-RUNX1.

Conclusion . Thus application of conventional set of immunological markers does not allow reliable distinguishing this patients’ subgroup. However antibodies panel enlargement, high degree of flow cytometry standardization and additional analytical methods can potentially improve applicability of antigen profile analysis for separation of patients with translocation t(12;21)(p13;q22)/ETV6-RUNX1.