PREDICTIVE FACTORS FOR THE DEVELOPMENT OF MYELOSUPPRESSION DURING CHEMOTHERAPY FOR NEOPLASMS
Nikiforova H.A., Moskalenko I.P., Gaiseniuk L.A., Vasiliev L.Ya., Sukhina E.N., Maznik N.A.
Ukrainian Institute of Medical Radiology, 82,Pushkinskaya St, Kharkov, 61024, Ukraine,Fax: (0572)431 125, e-mail: nip@xniimr.kharkov.ua
Application of chemotherapy (CT) course in patients with neoplasm is associated with a toxic effect of cytostatics on the bone marrow that results in leukopenia and often requires interruption in treatment. In order to design an overall treatment plan and individualized CT schedules, prognosis and early detection of the hematopoietic system complications are of great importance.
Taking into account that a cytotoxicity mechanism of the majority of the chemotherapeutic drugs is due to their pharmacokinetics and pharmacodynamics and is involved in the damage to DNA structure, we have tried to evaluate the general role that DNA ability to repair and the chromosomal aberrations level of peripheral blood lymphocytes as well as the functional state of hepatorenal system may have in prediction of the risk of developing myelosuppression of cytostatic genesis.
Patient material consisted of 158 patients diagnosed for breast and ovary cancer and treated with CT. In parallel with the examination of hematograms, a group of patients had a 111In-citrin scintigraphy of the bone marrow. The undiluted blood samples were exposed to UV-irradiation to repair DNA synthesis and 3HT uptake level was determined in the presence of oxyurea. Functional state of the liver was assessed using a number of biochemical factors and dynamical 131I-sodium rose bengal hepatoscintigraphy, that of the kidneys - by renography or dynamical 131I-hippurane- or [99Tc]-renoscintigraphy.
A significant patient-to-patient variability has been revealed of the severity of myelotoxic effect of cytostatic drugs, manifesting itself both in the morphological characteristics of peripheral blood and bone marrow scintigraphy. In the persistent hematocytopenia ( the number of leucocytes < 2.5 x 109/l, hemoglobin: 60-100 g/l ), a reduced 111In-citrin accumulation has been observed in the main zones of myelogenic hematopoietic system, even to the point of disappearance of hematopoietic areas from a field of vision. The impaired DNA repair ability in the blood lymphocytes was recorded in 61% patients. It correlated with a suppression of T-lymphocytes functional activity during the course of treatment and was found to be independent of the number of courses carried out. In the end of the treatment course, the number of peripheral blood lymphocytes with chromosomal aberrations markedly increased (<10%) that is unfavorable prognostic factor for the development of leucopenia either during or in the end of repeat CT courses. The development of leucopenia during CT treatment was more often seen in the patients with a dysfunction of hepato-renal system that can be due to an impaired metabolism of the cytostatic agents and their enhanced genotoxic action on the leucopoiesis.
It can be concluded from the above that the reduced ability of DNA to repair in the peripheral blood lymphocytes and increased level of chromosomal aberrations in lymphocytes involved in circulation against a background of dysfunction of liver and kidney are the predictive factors for the development of hematopoietic system complications in patients undergoing CT treatment for breast and ovary cancer.
The data obtained may be helpful in individual prognosis of myelosuppressive effect of cytostatic agents during the course of treatment in oncological patients. They can be also used to make an adequate choice of modern drugs protecting the hematopoetic cells.
For archive of summaries of bio-medical researches from Kharkov (Ukraine) universities and institutes contact: Nataliya Babenko, Head of Department of Physiology of Ontogenesis, Institute of Biology, Kharkov National University, e-mail: babenko@univer.kharkov.ua, fax: (0572)352923.