STUDY OF CHANGES IN HEMATOLOGICAL INDICES AGAINST THE BACKGROUND OF HEMATOSUPPRESSION CAUSED BY CYCLOPHOSPHAMIDE

Abstract

Summary. Hematosuppression caused by the action of cytostatic drugs belonging to the group of alkylating compounds in hematology is a common phenomenon, with compensation for this condition due to the appearance of areas of extramedullary hematopoiesis (EMH) in peripheral hematopoietic organs. Assessment of changes in hematological indices that occur during EMH is aimed at developing additional diagnostic criteria for diseases of the blood system.

The aim of the study – to investigate changes in peripheral blood hematological indices in cyclophosphamide-induced hematosuppression.

Materials and Methods. The study was performed on 30 adult mature Balb/c mice with an average weight of 25 g with a division into two groups of intact and experimental 15 mice in each. For the induction of extramedullary hematopoiesis, a mobilization protocol developed by the Department of Pathology and Developmental Biology of Stanford University was used [5]. Animals of the experimental group on the first day of the experiment were injected intraperitoneally with a bolus dose of cyclophosphamide ("Endoxan" manufactured by "Baxter Oncology GmbH" (Germany)) – 200 mg/kg, followed by three days of intraperitoneal injections of human recombinant granulocyte-colony manufacturer Dr. Reddy's (India)) in a dosage of 250 mcg/kg.

Evaluation of hematosuppression caused by  the combination of cyclophosphamide and G-CSF was performed remotely on day 21 of the experiment. Whole blood for the study taken from the heart cavity. The study of hematological indices was performed on a Horiba Yumizen H500 analyzer.

Results. Full compensation of anemic manifestations caused by hematosuppression on the 21st day of the experiment was revealed, which indicates a significant (p˂0.001) increase in the absolute number of erythrocytes by 119.34 %, with preservation of morphometric parameters within normal limits in a new population of erythrocytes and a slight increase in their heterogeneity. In the experimental group coefficient of variation by 16.12 % (p<0.001) and the standard deviation by 8.72 %. The change in platelet homeostasis consisted in forming an excessive amount of large platelet fraction in the experimental group of animals by 52.23 % (p<0.001) compared with the intact group of animals. There was a slight decrease in mean platelet volume of 7.57 % (p<0.001). Immunosuppression caused by cyclophosphamide leading to acute forms of neutropenia on day 21 of the experiment was fully compensated, as evidenced by an increase in the absolute number of neutrophils in 14.5 times the experimental group of animals. Among myeloid cells of the leukocyte lineage, there is increase in lymphocytes, monocytes, eosinophils and basophils by 60.32 %, 66.99 % 68.75 % and 76.39 % respectively.

Conclusions. Based on changes in hematological indices of peripheral blood, we found an increase in hematopoiesis of myeloid and megakaryocyte cells with compensation for hematosuppression caused by cyclophosphamide on day 21 of the experiment. In animals of the experimental group, increased erythropoiesis with compensation of anemic manifestations, activation of platelet hematopoiesis, and overcoming immunosuppression caused by cyclophosphamide G-CSF injections was confirmed, which was confirmed by a 14.5-fold increase in NEU.