A method of predicting the course of chronic myeloid leukemia

 

(57) Abstract:

The invention relates to medicine, namely to Hematology. A method of predicting the course of chronic myeloid leukemia is the definition of peripheral blood leukocytes in peripheral blood and bone marrow of the patient simultaneously determine the energy of taxis leukocytes (ETL), and when the gradient value ETL 0.05 and below determine the risk of disease progression is minimal, when the value from 0.06 to 0.15, the risk of progression is defined as the average, and when the gradient value above 0.15 risk of progression is defined as the maximum. Effect: method allows to simplify the prognosis and to predict the course of the disease until the appropriate progression of clinical and morphological features, as well as ensures the timely appointment of adequate therapy. 1 PL.

The invention relates to medicine, namely to Hematology.

It is known that the chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease, parental cell which is a primitive multipotential stem cell-predecessor mielo the most common hematological disease with fatal outcome. When monitoring patients with this diagnosis are of great importance criteria by which one can predict the course of disease for timely therapy changes.

The number of known approaches using multivariate analysis on the basis of which attempts are made to prognosis of CML.

Sokale with co-workers, watching 625 patients aged less than 45 years, given the size of the spleen, platelets, hematocrit value, percentage of blasts in peripheral blood and sex of patients, identified 3 risk groups. Eventually it was determined the formula for the magnitude of risk for each patient based on clinical and haematological parameters at the time of diagnosis. It is of great importance when choosing such treatments, as bone marrow transplantation or intensive chemotherapy [9, 10]. Further careful analysis were subjected to the most successful clinical prediction system to determine reliable signs that help in forecasting the course of CML[3, 6, 10, 12]. The authors have identified groups of low, intermediate and high risk by the number of adverse factors, which were as follows: age over 60 years, spleen more than 10 cm from under the costal arch, be 4-th group, which includes patients with one of the credited signs: cytogenetic characters clonal evolution of CML, blastemal more than 15%, basophilia more than 20%, the total percentage of blasts and promyelocytes more than 30%, platelet count less than 100×10⁹/L. In this group of patients mortality during the first year amounted to 29% [7].

Russian author, working to create a prognostic systems in CML is N. D. Khoroshko, which has identified 3 categories of risk CML, taking as prognostic criteria level of leukocytes, the number of blasts, the total number of plasmic order has been revealed and promyelocytes, the percentage of basophils, platelets, hemoglobin and the size of the liver and spleen [2]. Applying the scheme, based on these criteria, for a differentiated approach to treatment is shown a statistically significant increase in chronic phase. In addition to systems that include criteria which characterize the clinical features of the disease, recently proposed a more complex scheme based on cytogenetic and immunological analysis [13, 11].

A prototype of the invention adopted our method developed by N. D. Khoroshko “prognostic Factors in chronic malaleuca the point (s), which is difficult enough to lead to a single numerical value, because their relationship is nonlinear and, respectively, the coefficients of the value of the parameters change with new research, not having sufficient reliability.

Our proposed method of prognosis of CML uses as the starting point of the calculation is just one indicator - energy taxis leukocytes (ETL), measured simultaneously in the peripheral blood and bone marrow of the patient.

The technical result - the application of the method of determining the ETL enables prognosis of the disease until the appropriate progression of clinical and morphological features, which in turn allows to start appropriate treatment.

The invention consists in the following.

ETL is determined according to the method of A. B. Peskov (RF patent No. 2154829, BI No. 23, 2000), which consists in the separation of the cellular elements of the tissue suspension, incubating them at a temperature of 37°C for 24 h in the thin-walled capillaries in a vertical position (control series) and in the angular rotor with continuous rotation (experimental series). In subsequent measured the length of leukocyte is t the calculation of the gradient of the ETL, which is numerically expressed by the indicator, determining, according to our data, the prognosis for CML.

The table demonstrates the importance of the gradient ETL for prognosis of the disease.

In benign chronic phase indicator has a value close to zero (-0,44±0,27). In the phase of acceleration gradient ETL increases sharply up to 0.30±0,19 further stores a tendency to increase (in the terminal phase - 0,36±0,16).

As can be seen from the table, the course chemotherapy leads to a decrease of the gradient ETL, however, the indicator does not reach the values of the chronic phase of the disease.

In all cases, our observations gradient ETL changed, anticipating the appropriate clinical and laboratory indicators for 2-4 weeks, with high accuracy pointing to beginning the progression of the pathological process. Our studies suggest that

when the gradient value ETL 0.05 and lower risk of disease progression is minimal, the patient requires dynamic monitoring without the use of chemotherapy;

when the gradient value ETL from 0.06 to 0.15, the risk of disease progression average, you need n the SC of disease progression maximum, the patient requires a course of chemotherapy.

The application of our method:

to simplify the prediction of the disease;

To predict until the progression of the disease, clinical and morphological features.

LITERATURE

1. Abdulkadyrov K. M. Moiseev, S. I., E. Shcherbakov,, Balashova C. A., Glazunova T. C., Rukavice O. A., Martinkevich I. S., Gritsev S. C., Blinov, M. I. // the Experience of using reaferona (CC2-interferon) for treatment of patients with chronic myeloid leukemia. // Ter. Archive, 1995, No. 36, S. 59-63.

2. Baryshnikov, A. Y., Morozov, L. F., Volkov M. A., and others // Clinical-morphological characteristics of immunological variants of blast crisis of chronic myeloid leukemia // Hematol. and transfusion. 1985, No. 11, S. 12-16.

3. Kozinets, I., Kovalev, L. G., A. Polyanskaya Meters, etc. // Clinical and cytological diagnosis of hematological malignancies // Hematol. and transfusion. 1984, No. 5, S. 3-12.

4. Pogorelov Century. M // S-segments of chromosomes hematopoietic cells in normal and leukemia // abstract. Kida. Diss., M, COLIC, 1982, S. 1-5.

5. Khoroshko N.D. // Modern therapy of chronic myeloid leukemia //. Abstract of Prof. Diss., Moscow, GNTS Russian Academy of medical Sciences, 1992, S. - 46.

is orosco N. D., Mokeev R. A., E. Abakumov N., Nemchenko I. S., Semenov E. A., Zakharov A. C., Kobzev Y. N. and other Diffuse brain damage when hypereosinophilia variant Ph - negative, BCR/ABL - positive variant of chronic myeloid leukemia.// Hematol. and transfusion., 2000, No. 2, S. 30-34.

8. Snitzer H. C. // the Value of immune complexes and characterization of blast cells in chronic myeloproliferative diseases // abstract. dis. Kida. the honey. Sciences. - Kyiv, 23 C., 1983.

9. Jonuleit So, Perschel S., Schwas R., et al. // Bcr-abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors. // Brit. J. Haematol. 1998, v.100, p.295-303.

10. Maeyer E. // Interferon and other regulatory cytocins // NY., 1988, p.201.

11. McDonnell T., Raymond E. Meyn, L. E. Robertson // Implications of apoptotic cell death regulation in cancer therapy. // Cancer Biology, 1995, v.6, p.53-60.

12. Schwab, S., Peschel C., D. Despres, et al. // Deficient cell cycle control in myeloid leukemia. // Cytokines and Mol. Therapy, 1995, v.1, p.281-288.

13. Guilhot F., Dreyfus Century, M-c Desmareat, C. Giroud, Huret J. // Combined therapy of interferon and chemotherapy in chronic myelogenous leukemia. // Nouvelle Revue Francoise d” Mematologie, 1989, v.31, 2, R. 171-173.

A method of predicting the course of chronic myeloid leukemia, consisting in the determination of leukocytes in the peripheral blood, characterized in that in the peripheral blood and bone marrow of the patient simultaneously determine the energy t is minimum, when the value from 0.06 to 0.15, the risk of progression is defined as the average, and when the gradient value above 0.15 risk of progression is defined as the maximum.