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Oncohematology

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Vol 14, No 2 (2019)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/1818-8346-2019-14-2

HEMATOLOGIC MALIGNANCIES: TREATMENT, SUPPORTIVE CARE

8-12 9644
Abstract

The objective of study is to estimate the efficiency of extracorporeal free light chains of immunoglobulin elimination in patients with monoclonal gammopathies (n = 12) during hemodialysis using selective filters.
Materials and methods. A blood and dialysate free light chains concentrations change was criterion of efficiency.
Results and conclusion. The selective free light chains filtration give the possibility of an adequate anti-tumor therapy, could prevent the development of irreversible renal failure and hypoalbuminemia.

13-23 11841
Abstract

Objective: to clarify the conditions for the occurrence of thrombosis and assess the effect of anticoagulant therapy on the survival and outcome of thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia (ALL) receiving program chemotherapy.

Materials and methods. The study included 592 patients with ALL received program chemotherapy from 2008 to 2017 in the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Minsk, Belarus). Of them, in 42 patients various localization venous thrombosis was detected at different therapy phase.

Results. The cumulative detection rate of thrombosis was 7.5 ± 1.1 %. The use of pegelated asparaginase (PEG-asp) at a dose of 1000 IU/m2 in induction therapy increased the relative risk of thrombosis in the first 5 weeks of treatment by 3 times (relative risk 3.4; 95 % confidence  interval 0.98–11.9), compared to patients not receiving PEG-asp. The cumulative detection rate of thrombosis in patients with the post-induction L-asparaginase (L-asp) 25,000 IU/m2 regimen was 14.7 ± 2.6 %, which was higher (p = 0.0536) than when using L-asp in other dosing regimens. In addition to ALL as the main disease, taking chemotherapy drugs, other risk factors for thrombosis (thrombophilia, the presence of antiphospholipid antibodies, a decrease of natural anticoagulants activity) in various combinations were in half (23 of 42) patients with venous thrombosis. Therapeutic dose of low molecular weight heparins (LMWH) 150–200 IU/kg received 30 patients. Reduced for the period of thrombocytopenia from 100 to 35 × 109/L for up to 4 weeks, a daily dose of LMWH was received by 12 patients. The dose of LMWH was reduced in proportion to the blood platelets count. After the recovery of the platelet count of more than 100 × 109/L, patients continued treatment of LMWH in a daily dose of 150–200 anti-Xa IU/kg. Reducing of LMWH dose during thrombocytopenia period did not affect the outcome of thrombosis (χ2 = 0.494; p = 0.78). Among 42 patients with thrombosis, 38 completed maintenance therapy, eventfree survival was 83.0 ± 8.0%, which did not differ (p = 0.654) from that (81.0 ± 2.0 %) in patients without thrombosis. 

Conclusion. The presence of venous thrombosis with the use of LMWH as antithrombotic therapy did not lead to a decrease in the event-free survival of ALL patients, compared with those without thrombosis. Reducing the therapeutic dose of LMWH did not affect the outcome of thrombosis in the analyzed groups.

24-28 9816
Abstract

Venous thromboembolism is not a rare complication in children with cancer. Despite the advantages of the treatment of venous thromboembolism there is still a probability of venous thromboembolism recurrence. In adult patients with cancer venous thromboembolism recurrence an influence on the lower survival rate. In children with cancer venous thromboembolism recurrence is a rare complication, but it can significantly reduce the quality of life. Risk factors of venous thromboembolism recurrence in children with cancer are not properly investigated.

29-40 10971
Abstract

The landscape of multiple myeloma treatment transformed at the last 15 years by the introduction of novel agents (bortezomib, lenalidomide) and wide application of autologous hematopoietic stem cell transplantation, which have prolonged the survival of multiple myeloma patients. Despite the fact that multiple myeloma remains an incurable disease due to the new options, the median overall survival of patients with multiple myeloma in Russia in 2006–2016 was about 55–68 months. Drug resistance and clonal evolution remain a problem. The novel proteasome inhibitors (carfilzomib, ixazomib) differ in chemical structure and pharmacological characteristics. Thereby the next-generation proteasome inhibitor (IPs)-based regimens (KRd (carfilzomib, lenalidomide, dexamethasone), IRd (ixazomib, lenalidomide, dexamethasone), and Kd (carfilzomib, dexamethasone)) are emerging as new standards for the treatment of patients with relapsed and/or refractory multiple myeloma. In a randomized trial phase 3 ENDEAVOR, carfilzomib demonstrated improved survival in direct comparison to bortezomib. The dose-dependent activity of carfilzomib demonstrated in the study of A.R.R.O.W. Аctivity of ixazomib is comparable to that of bortezomib, the oral method of administration and the absence of neurological toxicity, allow for long-term control of the disease. The new PIs are an important advance in relapsed and/or refractory multiple myeloma treatment, increasing survival, response rate and quality of life, even in subgroups of patients with poor prognosis. This review summarizes the main pharmacological properties, mechanisms of action and clinical outcomes of major clinical studies with these agents. A separate issue discusses the problem of overcoming new proteasome inhibitors of drug resistance to bortezomib.

RARE DISEASES

41-47 10950
Abstract

Currently, the diagnosis of acute myeloid lekemia is based on the standards of morphological studies and immunophenotyping of the bone marrow. The manifestation of the disease can be accompanied by extramedullary lesions, which are difficult to verify. The article presents a case of diagnosis of acute myeloid lekemia in an elderly w oman, occurring with a leukemic lesion of the small in - testine. Morphological studies and immunophenotyping of small intestine biopsy revealed acute myeloid lekemia blast tumor cells. Difficulties of examination in such cases lead to late revealing of leukemic infiltrates of rare localization and significantly worsen the prognosis. 

BASIC RESEARCH

48-58 9776
Abstract

The study objective is to investigate the features of subpopulational composition of mobilized hematopoietic stem cells in peripheral blood (PB) and leukocyte concentrates (LC) in adult patients with oncohematological pathology and donors.

Materials and methods. In 80 patients with hemoblastoses, expression of CD38, HLA-DR and CD143 (angiotensin-converting enzyme) was measured in PB and LC CD34+CD45low cells. The control group included 10 PB and 14 LC samples from healthy donors. Analysis of PB was performed prior to mobilization of hematopoietic stem cells (HSC) and on the day of leukapheresis prior to HSC collection. LC samples were examined at day 1 after HSC collection.

Results. CD143 is expressed on CD34+CD45low cells both prior to mobilization and after it in all patients and donors, but CD34+CD45lowCD143+ cell counts varied depending on diagnosis and mobilization regimen. CD143+ expression on CD34+CD45low cells was significantly higher in patients who received combination of chemotherapy and granulocyte colony-stimulating factor compared to donors and patients with multiple myeloma who received only granulocyte colony-stimulating factor. Along with elevated CD34+CD45low cell count after hematopoiesis stimulation, CD34+CD45lowCD143+ cell counts also increased. It was shown that mobilized HSC almost completely lacks a fraction of early CD34+CD45low progenitor cells not expressing CD38, HLA-DR. Prior to hematopoiesis stimulation among CD34+CD45low cells, CD38+HLADR–cell fractions are prevalent, but after mobilization CD38–HLA-DR+ cell counts increased. No differences between CD34+CD45lowCD143+cell counts in patients with multiple myeloma depending on disease status, sex, age or number of chemotherapy courses prior to HSC mobilizationwere observed.

Conclusion. Expression of angiotensin-converting enzyme on CD34+ cells in PB before and after HSC mobilization and in LC was observed. The cell counts varied depending on diagnosis and mobilization regimen.

59-69 9584
Abstract

Despite continuous attempts to improve therapy, the outcomes of acute myeloid leukemia remain almost unchanged over last decades. Drugs made with a more complete understanding of the biology of acute myeloid leukemia do not equal the hopes for better prognosis. The best results are achieved only with high-dose chemotherapy, which is only possible for a limited number of patients. High phenotypic and genotypic heterogeneity of acute myeloid leukemia defines the relevance to develop personalized approaches to therapy, including those based on determination of individual drug sensitivity of blast cells.
This article presents the results of developing an ex-vivo model of acute myeloid leukemia, as well as testing of two in vitro sensitivity assessment methods: evaluation of the genotoxicity of drugs in the micronucleus test and vitality and sensitivity to chemotherapy in sorted blast cells. Prospects of individualized therapy of acute myeloid leukemia were determined based on introduction into clinical practice and continuing the research.

70-85 10065
Abstract

Tissue factor, being the main initiator of the blood coagulation in vivo, is involved in a number of physiological processes, such as angiogenesis or cell migration. These processes are not only significant for normal physiology, but also play a role in the development and progression of oncological diseases. This review presents data on the structure of tissue factor, its expression in normal conditions and in cancer, its role in thrombosis development associated with cancer, in angiogenesis and in metastasis. The involvement of tissue factor in such a wide range of physiological processes important for the progression of cancer makes it an attractive target molecule for therapy.



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ISSN 1818-8346 (Print)
ISSN 2413-4023 (Online)