Dermatological toxicity of EGFR inhibitors: pathogenetic rationale and an algorithm for acne-like rash correction

Therapy with epidermal growth factor receptor (EGFR) inhibitors is inevitably accompanied by the phenomena of dermatological toxicity. Being, on the one hand, a favorable prognostic factor for the effectiveness of anticancer therapy, these adverse events are one of the most frequent indications for treatment withdrawal. This article presents the clinical characteristics of a wide spectrum of dermatological adverse events, as well as the pathogenetic rationale for their correction. Algorithms for prescribing of external and systemic therapy based on the assessment of severity of skin lesions and skin appendages involvement are presented.

Prevention and treatment of thrombosis in cancer and oncohematological patients

The purpose of the review is to highlight the current possibilities for the prevention and treatment of venous thrombotic complications in patients with cancer.The data of 52 scientific sources published in the Russian and foreign press in 1997–2020 are considered.Cancer patients are at high risk of thrombotic complications, which worsen the outcome of anticancer treatment and are one of the leading causes of death. Thrombosis in an oncological patient increases the risk of death by 30 times, which is associated with fatal thromboembolism and a more aggressive course of the disease. The leading role in the pathogenesis of thrombotic complications is played by disorders in the hemostasis system caused both by the tumor itself and by therapy. Low molecular weight heparins are considered the basis for specific prophylaxis of thromboembolic complications in cancer patients. The use of low molecular weight heparins after surgery and during chemotherapy effectively reduces the incidence of venous thrombosis. Direct oral anticoagulants are promising drugs for oral administration and are indicated as one of the treatment options for patients with tumor-associated thrombosis with a low risk of bleeding and no drug interactions with ongoing systemic chemotherapy.

Obesity in children with acute lymphoblastic leukemia in remission: the evaluation of causes, hidden nutritional deficiency and the experience of its correction by using artificial enteral nutrition

Background. Antineoplastic treatment can have late toxic manifestations that can often appear after end of treatment. Children after treatment for acute lymphoblastic leukemia (ALL) have a risk of developing both obesity and undernutrition, which may be concealed by increased fat mass.Objective: to explore the incidence of obesity and hidden undernutrition in children with ALL and to describe the effect of enteral feeding using in these children.Materials and methods. In a retrospective study the data of 62 children with obesity that was revealed by standard examination was analyzed. The criterion of obesity was increased value of fat mass received by bioimpedance analysis. For this evaluation Russian bioimpedance analysis standards were used. Additionally, the included data were following: presence of endocrine pathology, weight change during latter 6 months before admission, physical activity and alimentary characteristics (usual regimen and structure of daily feed).Results. Only 54.8 % of patients with an actual excess of fat body mass index detected obesity (Z‑score higher than +2.00) and another 29 % body mass index was within the normal range (Z‑score from –1.00 to +1.00). This was the result of a tissue imbalance: reduce fat‑free mass. Some patients were diagnosed with insulin resistance and hyperinsulinemia. 83.7 % have a completely passive lifestyle. 49.0 % almost do not eat fruits and berries, 79.6 % – vegetables and 91.8 % – fish and seafood. Frequent intake of sweet dishes – 22.4 %, sausage products – 49.0 %, bakery products – 42.9 %, dishes from fast food restaurants – 42.9 %. 55.1 % of patients had more than 5 meals a day, while 18.4 % – less than 3. In or‑ der to correct hidden nutritional deficiencies, 22 patients received artificial nutritional formulas. They had a significant increase in fat‑free mass and a decrease in fat, in comparison with those who did not receive enteral feeding.Conclusion. Treatment‑associated factors, physical activity and alimentary causes play an important role in formation of not only obesity, but also hidden nutritional insufficiency in children with ALL after treatment. Enteral feeding using artificial polymeric formulas showed its effectiveness. An integrated and multidisciplinary approach to solving the problem is appropriate of prevention and treatment of obesity.

Renal failure in patients with hematological malignancies (literature review)

Dysfunction of the natural detoxification organs remains a significant problem in patients with hematological malignancies. The reasons for the development of renal failure are associated with the individual characteristics of the malignant process, the patient’s comorbid background, the toxic effects of anticancer treatment and its complications. The efficacy of many anticancer drugs correlates with their dose, an increase in which is associated with increased toxic effects on healthy organs, including the kidneys. The main reasons for the renal failure development in hematological cancer patients and syndromes that prevent adequate antitumor therapy are considered. Diagnostic algorithm optimization and supportive intensive care of acute renal failure is the key to the successful application of highly effective modern protocols of drug anticancer treatment.A special group is represented by patients suffering from monoclonal gammopathies with acute renal injury and hyperproduction of immunoglobulins free light chains. Renal failure can be the onset and dominant clinical manifestation of multiple myeloma in 18–56 % of cases, of which 10 % require programmed hemodialysis. Antitumor therapy in presence of renal failure is limited, and in some cases impossible, while the renal function recovery is associated with an increase in survival.Organ damage in oncohematological patients can be a manifestation of paraneoplastic syndromes. Tumor lysis syndrome is an urgent problem of oncohematological practice associated with the development of acute renal injury and high mortality.The development of organ failure in oncohematological patients causes significant difficulties in antitumor therapy; a combination of organ dysfunction and the resulting change in anticancer therapy regimens worsen the prognosis. Modern methods of organ failure prevention and treatment can successfully solve complex clinical problems.

Key issues of patient safety during anticancer drug treatment in a day hospital and outpatient setting

Background. In the context of the ongoing COVID-19 pandemic, the vector of healthcare development is aimed at minimizing contacts among citizens, which is especially important for cancer patients, given the immunosuppression caused by cytostatics.The objective of the review is to present the development prospects of hospital-substituting technologies for drug antitumor treatment. Two main components are considered that allow effective and safe infusion of anticancer drugs in a day hospital: central venous access devices and infusion pumps, various types of these devices, their safety and experience of use today are described.Materials and methods. We searched for available literature published in PubMed, Medline, eLIBRARY, Cochrane Library, CyberLeninka, Global.health, etc. 42 sources were found and analyzed, published from 2002 to 2021.Results. Outpatient anticancer drug treatment is a real alternative to hospital stay, based on many years of world experience. The qualifications level of medical personnel involved in the treatment process should allow early monitoring of various adverse events development. With the ongoing COVID-19 pandemic, it is important to ensure the continuity of the treatment process while minimizing risks to the patient.Conclusion. With a careful approach and adequate infrastructure availability, drug treatment in a day hospital can reduce the burden on round-the-clock stay hospital and positively affect the patients’ quality of life and their compliance with treatment.

Molecular serological characteristics of ABO system A antigen

Background. One of the polymorphic antigens in the ABO system is antigen A, which includes many allelic variants with different expression. Immunological methods for determining the blood group of the ABO system have limitations in their use, including due to the presence of weekly expressed antigens in humans. For the correct determination of blood group according to the ABO system, genetic typing is becoming increasingly important. 89 alleles of the ABO*A gene are known. Knowledge of ABO*A gene polymorphisms and their prevalence contributes to the prevention of errors in determining the blood group of donors and recipients.Objective: to describe variants of ABO*A gene alleles in Russians and serological characteristics of the antigens encoded by them.Materials and methods. The blood of 14,000 people was examined. The blood group was determined using anti-A, anti- Aweak, anti-B, lectin (anti-A1) and gel cards. A molecular study of ABO*A gene polymorphisms was conducted in 151 people. Polymerase chain reaction with sequence-specific primers and direct Sanger sequencing were used.Results. 7 different ABO*A alleles were detected, including the ABO*A1.01 and ABO*A1.02 alleles. In 118 individuals with a weak A antigen, the ABO*A2.01 allele was the most frequent (87.29 %). Rare alleles ABO*A2.06 (5.93 %), ABO*AW.06 (4.23 %), ABO*A2.09 (0.85 %) and ABO*Ax (1.70 %) were found. Serological characteristics of A antigens variants depending on genotypes are described, variants A1, A2, A3 and very weak A were detected. Extraagglutinins α1 were absent in all persons with weakened A antigen.Conclusion. Small or mixed agglutination with Coliclones or red blood cell stratification in the gel suggest the presence of antigen A with weakened expression. Modern molecular methods make it possible to identify rare gene alleles and genotypes. Erythrocyte genomics helps to resolve the ambiguity of the serological results allows understanding the true mechanisms of particular phenotype formation and makes a contribution to ensuring the immunological safety of blood components transfusions.

Based on the seminar materials of the “Oncohematology” Journal Experts Council “Modern approaches to the refractory multiple myeloma treatment”

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Results and prospects for the development of supportive therapy in Russia. Based on the materials of the first Best of MASCC conference in Russia

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Polymorphism of ABO*O alleles and its clinical significance

Background. 62 ABO*O alleles of the ABO system are known. Some ABO*O alleles may be accompanied by the presence of residual A-glycosyltransferase activity in people of group O, which may lead to errors in determining the blood group. This confirms the important clinical significance of the ABO*O allele polymorphism. Knowledge of ABO*O gene polymorphisms and their prevalence contributes to the prevention of errors in determining the blood group of the ABO system.Objective: to study allele variants of the ABO*O gene in Russians.Materials and methods. The blood samples of 14,000 people were examined. The blood group was determined using anti-A, anti-Aweak, anti-B, lectin (anti-A1) and gel cards, as well as by cross-sectional method using standard red blood cells of O, A, and B groups. In one patient, the method of adsorption-elution with cold elution was used to identify a weak variant of antigen A, and the method of thermal elution was used to eliminate antigen- blocking plasma factors. Molecular determination of ABO*O alleles was performed in 130 individuals by polymerase chain reaction with sequence- specific primers and Sanger direct sequencing.Results. 13 allelic variants of the ABO*O gene were identified (10 with a typical deletion of c.261delG / N and 3 nondeletional alleles with polymorphism c.802G>A). Deletion alleles of ABO*O.01 were found in 92.85 % of the examined patients, nondeletion alleles of АВО*О.02 group – in 7.15 % of cases. The ABO*O.01.01 allele was detected with a frequency of 67.14 %, other deletion alleles – much less frequently: ABO*O.01.02 and ABO*O.01.11 – 5.71 %, ABO*O.01.26 – 5.00 %, ABO*O.01.12 – 4.30 %, ABO*O.01.13 and ABO*O.01.44 – 1.43 %, ABO*O.01.05, ABO*O.01.46, ABO*O.01.68 – 0.71 % each. Non-deletional alleles were found with the following frequencies: ABO*O.02.01 – 4.3 %, ABO*O.02.03 allele – 2.14 %, ABO*O.02.02 – 0.71 %. All individuals with the O group with the nondeletional allele had the Oαβ group, except for one patient (with the ABO*O.01.02 O.02.02 genotype), who had the Oβ group.Conclusion. For the first time, the immunogenetic characteristics of Russians are given according to ABO*O genes. Erythrocyte genomics helps to resolve the ambiguity of serological methods results and allows understanding mechanisms of different phenotypes formation. For the correct definition of natural isohemagglutinins and weak antigens variants should be used at least two different serological methods.

Immunocorrective treatment use in the prevention of hematological and infectious complications of chemotherapy in cancer patients

The article analyzes the use of immunocorrection of hematological toxicity that occurs during chemotherapy in cancer patients. Hematological toxicity, along with cardiotoxicity and hepatotoxicity often prevents the implementation of the entire planned volume of chemotherapy.Standard therapy (colony stimulating factor use) may not be always available and there is a need to develop new and more effective strategies for supportive care. Among the various methods and approaches, the most promising may be the use of systemic immunecorrecting therapy, the possibilities of which are far from being realized in oncological practice.The analysis of the studies summarized in this review demonstrates the effectiveness of the immunomodulator/immu‑ noadjuvant – azoximer bromide in hematological toxicity prevention in patients with various types of cancer.