Specific Features of Interactions between Megakaryocytic and Granulocytic Hematopoiesis Lineages and Myelofibrosis during the Acute Phase of Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia, and Multiple Myeloma.

The specific features of interactions between megakaryocytic and granulocytic hematopoiesis lineages and myelofibrosis were studied in patients with active phase (before treatment) of chronic myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. In patients with chronic myeloid leukemia, a direct correlation was found between the severity of both early and advanced myelofibrosis and the number of megakaryocytes in the bone marrow irrespectively of the type of the bone marrow tumor. The parameters of granulocytic hematopoiesis lineage were higher in myelofibrosis. In patients with chronic lymphocytic leukemia and multiple myeloma, negative correlations between the severity of early and advanced myelofibrosis and the number of megakaryocytes in the bone marrow and platelets in the peripheral blood were found. In chronic lymphocytic leukemia, negative correlations between the severity of early and advanced myelofibrosis and the number of neutrophils in the bone marrow and peripheral blood were detected. In patients with multiple myeloma, negative correlations between the severity of advanced myelofibrosis and number of neutrophils in the bone marrow and peripheral blood were detected.

Quantitative Analysis of Red Bone Marrow Microenvironment Cells in Patients with Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphocytic Leukemia in the Dynamics of Chemotherapy.

We performed comparative analysis of quantitative changes in the populations of bone marrow microenvironment cells in patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia in the debut, during response to chemotherapy, and during relapse/progression/loss of response. It was shown that in the active phase of hemoblastoses, the number of reticular cells and fibroblasts in trephine biopsy specimens was higher than in the phase of response to chemotherapy and than in the control group. In patients with relapse of multiple myeloma and loss of response in chronic myeloid leukemia, the percentage ratio of adipocytes in the bone marrow significantly (by 9-13-fold) increased. In addition, endotheliocytes appear in the active phase of all hemoblastoses in trephine biopsy specimens, while in the phase of response to chemotherapy and in the control group, these cells were absent. The revealed quantitative changes in bone marrow stromal cells can be taken into account during assessing the phase of hemoblastosis and effectiveness of chemotherapy.

Connection between Parameters of Erythron System and Myelofibrosis during Chronic Myeloleukemia, Multiply Mieloma, and Chronic Lymphatic Leukemia.

Clinical and morphological investigation of myelofibrosis was performed in patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia by analyzing the morphometric parameters of trepan-biopsy material. The correlation between changes in the parameters of erythron system and distribution of myelofibrosis were analyzed. In patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia, the maximum suppression of the erythron was observed against the background of severe myelofibrosis. The degree of erythron inhibition correlated with distribution of the fibrous tissue in the bone marrow. In patients with onset of chronic phase of chronic myeloid leukemia and active phase of multiple myeloma, the total number of erythroid cells was lower than in active phase of chronic lymphocytic leukemia irrespective of the degree of myelofibrosis. Erythrocyte count and hemoglobin content in the peripheral blood were lower in patients with multiple myeloma and chronic lymphocytic leukemia in comparison with the corresponding parameters in patients with chronic myeloid leukemia irrespective of the severity of myelofibrosis.

Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases.

Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.

Clinical Morphological Studies of Myelofibrosis with Different Types of Bone Marrow Involvement in Patients with Chronic Lymphocytic Leukemia.

Clinical-morphological study of myelofibrosis was carried out in patients with chronic lymphocytic leukemia at the debut of the disease. Trephinobiopsy specimens of the ileac bone, aspirated specimens of the bone marrow, and peripheral blood smears were studied in 80 patients. Chronic lymphocytic leukemia was associated with myelofibrosis of different severity in 22.5% cases. Morphometric analysis of trephinobiopsy specimens showed that the severity (histology and dissemination) of myelofibrosis correlated with the type of tumor involvement of the bone marrow. Focal tumor involvement of the bone marrow predominated in trephinobiopsy specimens from patients without myelofibrosis, while patients with myelofibrosis developed mainly diffuse tumor infiltration, associated with the greatest dissemination of the initial and manifest myelofibrosis. No myelofibrosis was found in patients with interstitial tumor involvement of the bone marrow. The severity of the initial and manifest myelofibrosis directly correlated with the tumor involvement of the bone marrow and peripheral blood. Evaluation of the prognosis showed that initial myelofibrosis was associated with disease standing of 5.5 months, while manifest condition with a disease of 8.5 months and longer.

Blood microvesicles during chronic lymphoproliferative diseases.

The levels of CD19 (+) and CD20(+) microvesicles were estimated in the blood of patients with B-cell chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma by flow cytometry method. It was found that the number of B cell microvesicles is several times higher in patients than in volunteers. The level of CD20 (+) microvesicles directly correlated with the number of CD20(+) lymphocytes in patients with chronic lymphoproliferative diseases. Extramedullary tumors cells can be a source of CD19 (+) microvesicles.

Spontaneous and mitogen-induced cytokine production in lymphoproliferative diseases.

The levels of spontaneous and mitogen-induced production of pro- and anti-inflammatory cytokines were studied in patients with chronic lymphoid leukemia, non-Hodgkin's lymphocytic lymphomas, and multiple myeloma during the course of chemotherapy. Cytokine concentrations varied within a great range and did not conform to the normal distribution law. The levels of granulocyte and granulocyte-macrophage CSF were high during the debut, progress, and remission of the lymphoproliferative diseases. Imbalance of a wide spectrum of pro- and anti-inflammatory cytokines was observed during the debut and progress of the lymphoproliferative diseases, more often in chronic lymphoid leukemia and non-Hodgkin's lymphocytic lymphomas than in multiple myeloma.

Morphological characteristics of the central compartment of the erythron in aggressive and indolent non-Hodgkin's lymphomas.

Structural changes in cells of the central compartment of the erythron depended on tumor infiltration of the bone marrow. Cytostatic therapy was shown to improve quantitative indexes, but had no effect on morphological characteristics of the erythron. Examination of trepanobiopsy specimens from the iliac crest during chemotherapy revealed the existence of specific relationships between the erythron, other cells and tissues of the bone marrow, and tumor. Significant changes in the erythron were found during diffuse tumor infiltration and treatment with anthracycline antibiotics.

Morphometric study of trephine biopsy specimens in aggressive and indolent non-Hodgkin's lymphomas.

Morphometric study of the erythroid stem was performed in aggressive and indolent non-Hodgkin's lymphomas vs. other cells and tissues of the bone marrow (including the tumor tissue) before chemotherapy. Hypoplasia and abnormal maturation of the erythroid stem were particularly pronounced in diffuse infiltration of the bone marrow, which did not depend on lymphoma aggressiveness. Hypoplasia of the erythroid stem was often observed during focal infiltration of the bone marrow with lymphoma cells (despite a smaller area of tumor tissue in aggressive lymphomas than in indolent lymphomas). A decrease in the relative area of adipose tissue, smooth resorption of bone tissue, and myelofibrosis are the major changes in the bone marrow microenvironment.