The Main Complications in Patients with Acute Leukemia during the Period of Myelotoxic Agranulocytosis

Annotation: Improvement of chemotherapeutic protocols and algorithms of accompanying treatment made it possible to increase the survival rate of patients with tumors of the blood system. Despite these advances, most of the cytostatic drugs currently widely used to treat patients with hemoblastosis, in addition to the antitumor effect, also cause myelosuppression and the development of granulocytopenia. Granulocytopenia is one of the main factors associated with infectious complications in patients with tumors of the blood system. The nature of infectious complications may differ depending on the duration of granulocytopenia. Keywords: agranulocytosis, immune agranulocytosis, myelotoxic agranulocytosis, acute lymphoblastic leukemias, level of persuasion of recommendations.

DEPENDENCE OF CHANGES IN THE HYGIENIC CONDITION OF THE ORAL CAVITY AND PERIODONTIUM IN CHILDREN WITH MALIGNANT TUMORS ON THE DURATION OF POLYCHEMYTHERAPY AND QUANTITIES OF CYTOSTATIC DRUGS

It is known that the course of cancer and chemotherapy adversely affect the components of homeostasis of the oral cavity, which causes stomatotoxicity. However, scientific publications have not yet provided generalized results of research on the pathogenetic mechanisms of the dental pathology formation during chemotherapy, which constitutes the relevance of this publication. The aim of the research was to study the effect of different regimens of the second course of chemo- therapy on the hygienic condition of the oral cavity and periodontium in children with malignant tumors of the abdominal cavity. The dissatisfaction with our results obtained after the first course of chemotherapy on various regimens prompted us to further research. A survey of two previously formed clinical groups was performed. All of them resumed the treatment in the oncohematology department of the Poltava Children's City Clinical Hospital following a 3-4 week break between courses. Each patient was treated according to an individual program but in the absence of dental care. The dental status was assessed using the Green-Vermillion, Papillary-Marginal-Alveolar (PMA), and Pa- pilla Bleeding Index. The study of cytograms from the surface of the gingival margin of the frontal part of the mandible was carried out taking into account the methodology developed by our department's staff. The calculation was per- formed in 10 visual fields. Statistical processing was performed according to standard conditions. Research results and their discussion. It should be noted that in the comparative aspect, the indexes of Green-Vermillion, PMA, and RВI at the end of the first year were 1,8, 1,3, and 1,6 times worse than in the second observation group which received more cytostatic drugs. At the end of the second course of chemotherapy, the dryness of the mucous membrane accompanied by a decrease in oral fluid, which became viscous, was observed in 14 children (70,0%) of the first and 18 of the second group (85.7%). In addition, 15 people in the first group (75,0%) and 19 in the second one (90,4%) complained of pain and bleeding gums, which worsened when eating. At the same time, all children noted pain in the muscles that are adjacent to the lower jaw and involved in articulation. On external examination, only 2 children of the first (10,0%) and 1 of the second group (5%) had a red normal-coloured lip border, while the rest had exfoliation, cracks, and angular cheilitis. The oral mucosa mostly looked pale and pasty, except for 7 people of the second group (35,0%), who had manifestations of erythema. Localized erosions covered with fibrinous plaque were detected in 4 of these patients (20,0%) on the background of erythema. In addition, 12 children (60,0%) of the first group and 19 children of the second one (85.7%) showed swelling and redness of the gingival marginal edge, and the probing of the gingival sulcus provoked bleeding in all children of both groups. Green-Vermillion indexes increased by 1,5 and 1,7 times in the first and second groups, PMA increased by 1,4 times in both groups, and RВI was 1,4 and 1,5 times higher in the respective compared groups. The examination of cytograms revealed more pronounced changes in the second group where the epithelium with signs of intermediate stages of the differentiation prevailed. There was increased desquamation of the superficial layer of the gums and the increased number of peripheral blood elements, especially destroyed neutrophils. Thus, the generalization of the results obtained at the end of the second course of chemotherapy showed that the Green-Vermillion index was 1,8 times higher, and PMA and SВI indices were 1,4 times higher in the second observation group which received more cytostatics. That is, the severity of the manifestations of dental status disorders is directly proportional to the severity of the regimen. Conclusion. The prolongation of the second course of chemotherapy in children with abdominal malignant tumors provoked a significant deterioration of dental status. Major changes occurred in the group of children who received more cytostatic drugs simultaneously, which requires a balanced approach to designing differentiated treatment plans and prevention measures depending on the complexity of antitumor therapy regimens. Prospects for further research. The obtained results indicate the need to develop a set of differentiated treatment and prevention measures aimed at eliminating or improving changes in children that occur in the oral cavity under the influence of polychemotherapy.

Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs

Prooxidative therapy is a well-established concept in infectiology and parasitology, in which prooxidative drugs like artemisinin and metronidazole play a pivotal clinical role. Theoretical considerations and earlier studies have indicated that prooxidative therapy might also represent a promising strategy in oncology. Here, we have investigated a novel class of prooxidative drugs, namely chain-transfer agents, as cytostatic agents in a series of human tumor cell lines in vitro. We have found that different chain-transfer agents of the lipophilic thiol class (like dodecane-1-thiol) elicited half-maximal effective concentrations in the low micromolar range in SY5Y cells (human neuroblastoma), Hela cells (human cervical carcinoma), HEK293 cells (immortalized human kidney), MCF7 cells (human breast carcinoma), and C2C12 cells (mouse myoblast). In contrast, HepG2 cells (human hepatocellular carcinoma) were resistant to toxicity, presumably through their high detoxification capacity for thiol groups. Cytotoxicity was undiminished by hypoxic culture conditions, but substantially lowered after cellular differentiation. Compared to four disparate, clinically used reference compounds in vitro (doxorubicin, actinomycin D, 5-fluorouracil, and hydroxyurea), chain-transfer agents emerged as comparably potent on a molar basis and on a maximum-effect basis. Our results indicate that chain-transfer agents possess a promising baseline profile as cytostatic drugs and should be explored further for anti-tumor chemotherapy.

Relationship between LDH and Mg in Monitoring of Hematological and Non-Hematological Malignant Diseases

Relationship between LDH and Mg in Monitoring of Hematological and Non-Hematological Malignant Disease Aurelian Udristioiu, Titu Maiorescu University of Bucharest, Faculty of Medicine, Department of Molecular Biology ABSTRACT Background Magnesium, which is the second most abundant into-cellular cation after potassium, plays a key role in regulating many cellular functions and enzymes, including ion channels, metabolic cycles, and signaling pathways. Aim of this study was to evaluate the correlation between the serum levels of lactate dehydrogenase (LDH) and magnesium (Mg) in patients diagnosed with hematological and non-hematological malignant diseases. Method We analyzed a cohort of patients (n = 75) comprising males (n = 36) and females (n =39) with a mean age of 57 years, who had cancer and were admitted to the oncology department. The biochemical parameters were measured running a Vitros 250 dry chemistry analyzer (Johnson & Johnson, USA) using the slides for multi-layer spectro-photometry measurements. These patients were closely monitored twice a week during treatment with specific cytostatic drugs and once a week during consolidation therapy, using specific tests for different types of cancer. In addition, with the cooperation of physicians and patients, they were performed along with hematological and biochemical tests, CBC with differential count and LDH and serum Mg levels, which can serve as markers for monitoring the progression of malignancies. Among the patients, 5 patients were diagnosed with lung cancer, 11 patients were diagnosed with breast cancer, 14 patients were diagnosed with colorectal cancer, 43 patients were diagnosed with chronic lymphocytic leukemia (CLL), 1 patient was diagnosed with acute promyelocytic leukemia (LAM-3) and 1 patient was diagnosed with chronic monocytic leukemia (CML). The CBC with the differential count, biochemistry samples, body radiography, ultrasound and computed tomography (CT) were used for the patient to establish the type of cancer diseases. An initial panel of monoclonal antibodies was used to determine the immune phenotypes of the subgroups of differentiated T cells and B cells. The diagnosis of LAM-3 was made based on blood smears, the examination of bone marrow (BM) aspirates, the evaluation of promyelocytes, (greater than 30% in BM), and the presence of a specific immune phenotype. Results The results were interpreted for each patient based on medical history, clinical and para-clinical examinations and other signs of malignant diseases. Among the patients in this study, 55 patients (73%) exhibited normal serum levels of Mg (normal range value = 1.60-2.3 mg/dL; mean value = 2.2 mg/dL; SD = 0.2; p = 0.02) following cancer therapy. Six patients (8%) exhibited low levels of Mg (range = 0.60-1.50 mg/dL; mean value = 1.05 mg/dL). However, 12 patients (16%) displayed high levels of serum Mg (range =2.6-3.27 mg/dL; mean value = 2.89 mg/dL). The levels of serum lactic dehydrogenase (LDH) were also evaluated in patients newly diagnosed with cancer and in patients with unfavorable responses to the cancer therapy (range = 240-1330 U/L; mean value = 787 U/L; SD =1.33; p = 0.002; normal values 135-225 U/L), (Table 1). Discussions The serum Mg level is increased via Mg²+ release from malignant tissues in patients with malignant disease prior to treatment with cytostatic drugs. In the different malignant diseases, the serum Mg values were high, normal or low, independent of the serum LDH values. The LDH levels remained elevated after initial cytostatic treatment until cancer remission. The number of chromosome copies in malignant tumors can be correlated with the total serum LDH values. LDH levels in cancer patients are elevated due to high levels of LDH-3 isoenzyme in patients with malignancies and high levels of LDH-4 and LDH-5 isoenzymes, elevated patients with cancer of liver, muscle, lung and tissue tissues. conjunctive. High concentrations of serum LDH damage the cell membrane. Thereafter, malignant cells become invasive and metastasizes. Conclusions Normal levels of Mg with moderately increased LDH levels were observed in all patients who had cancer that was in the regression phase following good responses to a specific cancer therapy. Low levels of Mg with high levels of serum LDH were observed in all patients with poor prognosis and metastases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The Dark Side of Platinum Based Cytostatic Drugs: From Detection to Removal

The uncontrolled release of pharmaceutical drugs into the environment raised serious concerns in the last decades as they can potentially exert adverse effects on living organisms even at the low concentrations at which they are typically found. Among them, platinum based cytostatic drugs (Pt CDs) are among the most used drugs in cancer treatments which are administered via intravenous infusion and released partially intact or as transformation products. In this review, the studies on environmental occurrence, transformation, potential ecotoxicity, and possible treatment for the removal of platinum cytostatic compounds are revised. The analysis of the literature highlighted the generally low total platinum concentration values (from a few tens of ng L−1 to a few hundred μg L−1) found in hospital effluents. Additionally, several studies highlighted how hospitals are sources of a minor fraction of the total Pt CDs found in the environment due to the slow excretion rate which is longer than the usual treatment durations. Only some data about the impact of the exposure to low levels of Pt CDs on the health of flora and fauna are present in literature. In some cases, adverse effects have been shown to occur in living organisms, even at low concentrations. Further ecotoxicity data are needed to support or exclude their chronic effects on the ecosystem. Finally, fundamental understanding is required on the platinum drugs removal by MBR, AOPs, technologies, and adsorption.

THE EFFECT OF CYTOSTATIC DRUGS ON THROMBOCYTOPOIESIS IN RATS WITH WALKER-256 CARCINOMA

Among malignant neoplasms of women, breast cancer (BC) takes the leading place and is the cause of high mortality and complications. Side effects in the form of anemia, thrombocytopenia, bleeding, etc. often develop during cytostatic therapy, which is the main method of treatment and prevention of further development of the oncological process. In this regard, the problem of reducing side metabolic disorders remains relevant and creates a search field for the use of drugs aimed at stabilizing functions, both at the cellular and organ levels. The aim of the study was to evaluate the effect of cytostatic drugs on thrombocytopoiesis in rats with WALKER-256 carcinoma. The study included 60 rats, which, depending on the type of treatment, were divided into 5 groups. A week after the start of chemotherapy, the greatest increase in the number of platelets was in the presence of liposomal ethylmethylhydroxypyridine succinate. We recorded that the myeloprotective effect was 1/3 better in liposomal ethylmethylhydroxypyridine succinate compared to its non-liposomal form. Therefore, individuals those receiving cytostatic drugs in the treatment of breast cancer need protection from myelopoiesis. In the studies carried out by us, it was shown that oxidative stress occurred in animals against the background of treatment with cytostatics. It was its rapid development that caused damage to the platelet cell membranes. In this regard, we have proposed a drug with a pronounced antioxidant efficacy. The introduction of an antioxidant into the generally accepted standard treatment of a tumor process has made it possible to experimentally select methods for delivering the drug to the targets of damage using liposomal forms. The study obtained data proving the effectiveness of the use of liposomal ethylmethylhydroxypyridine succinate (50 mg / kg), in contrast to its free form, which prevents the development of thrombocytopenia induced by the administration of cytostatic drugs to rats with Walker-256 carcinoma.