Chronic myelogenous leukemia

Chronic myelogenous leukemia is a tumor originating from a polypotent stem cell, which causes the involvement of all hematopoiesis cells in the pathological process in this disease. Almost all dividing cells of myelopoiesis( granulocytes, monocytes, megakaryocytes, erythrocaryocytes)( in 88-97% of patients), as well as lymphoblastic crises with the detection of the Ph-chromosome in blast cells, confirm pathognomonic for chronic myelogenous leukemia of an abnormal Ph-chromosome.

Three phases are distinguished during chronic myelogenous leukemia:

■ Slow, or chronic, phase usually lasts approximately 3 years.

■ Acceleration phase lasts 1-1,5 years. With appropriate treatment, you can return the disease to the chronic phase.

■ The final phase is the phase of rapid acceleration or blast crisis( 3-6 months), which usually ends in death.

Despite the defeat of all sprouts of the bone marrow, the main proliferating sprout, characterized by unlimited growth in the chronic phase of chronic myelogenous leukemia, is granulocyte. Increased production of megakaryocytes and erythrocaryocytes is less pronounced, it is observed less often.

Chronic myeloid leukemia is characterized mainly by the leukemia version of the flow. In the chronic phase, the number of leukocytes in the peripheral blood varies from 20 to 500x109 / L with a left shift of the leukocyte formula to myelocytes, promyelocytes and single myeloblasts. The sum of promyelocytes and myeloblasts is less than 15%.An important hematologic sign that appears already in the early stages of the disease is an increase in the content of basophils, as well as eosinophils of varying degrees of maturity( basophilic-eosinophilic association).If the number of immature forms( myelocytes, metamyelocytes) is small( 10-15% of the total number of granulocytes), differential diagnostics with a leukemoid reaction of the myeloid type is necessary.

The chronic phase of chronic myelogenous leukemia is characterized by hyperplasia of the red bone marrow. There is a marked predominance of granulocytopoiesis( leucoerythroblastic ratio more than 4: 1).Among granulocytes, young forms predominate-myeloblasts, promyelocytes, myelocytes. In the early stage of the disease, a combined increase in the content of eosinophils and basophils is possible. Gradually develops the oppression of erythropoiesis. The number of megakaryocytes at the onset of the disease is normal or even elevated. Morphology of granulocytes in chronic myelogenous leukemia has the following features: often reveal either abundant or very poor granularity of promyelocytes and myelocytes;the cytoplasm often shows signs of immaturity, differing in basophilia;sometimes there is a disproportion in the development of the nucleus and cytoplasm;very characteristic of anisocytosis. Maturation of granulopoietic cells is normal. The content of alkaline phosphatase in most mature leukocytes is sharply reduced. Anemia does not belong to the typical signs of the first

phase of the disease development and in most cases develops during the progression of the process. Nevertheless, sometimes subnormal Hb concentrations are noted from the very beginning. Anemia is normocytic and normochromic. The origin of anemia can not exclude the effects of hyperplastic spleen, as well as the latent flow of hemolysis. The number of platelets is normal or more often elevated during a longer period of the disease, thrombocytopenia occurs in the final phase or as a result of chemotherapy treatments. Megakaryocytes are small-lobed to single-core microforms, their number is increased.

The phase of acceleration of chronic myelogenous leukemia is characterized by the fact that with the help of previous therapy it is no longer possible to maintain clinico-hematologic parameters stable: there is a tendency to a gradual increase in the number of leukocytes;decreasing with increasing dose of the therapeutic drug, leukocytosis grows very rapidly with its decrease. The content of myelocytes and metamyelocytes in the blood increases, sometimes there are single promyelocytes and blast cells, hypertrombocytosis is often noted( the amount of platelets can increase up to 1500-2000x109 / l and higher).

In the final phase, chronic myelogenous leukemia acquires the features of a malignant tumor - a monoclonal tumor turns into a polyclonal tumor: a new cell population( blast cells or a large number of basophils, monocytes), which gradually acquires the features of increasing atypism( enlargement and ugliness of the nuclei)oppression of functionally normal germs of hematopoiesis, the yield of pathological hemopoiesis beyond the red bone marrow.

As a manifestation of the regularity of the tumor progression, the so-called blast crisis of the type of acute leukemia develops in the final phase of the disease, with a blast pattern of blood and bone marrow characteristic for the latter: more than 20% of blasts in blood and red bone marrow, the total content of blasts and promyelocytes exceeds30% in the peripheral blood and 50% in the bone marrow. The clinical picture of the disease carries features of acute leukemia. Deep anemia develops, thrombosis-mourning. The content of megakaryocytes in the bone marrow is decreasing. Peripheral blood appears in a large number of blast cells, mainly myeloblasts of an atypical form, but there may be monoblasts, erythronormoblasts, undifferentiated blasts, and even lymphoblasts. The affiliation of cells to one or another series is established by immunophenotyping, about a third of the crises are lymphoblastic.

Rarely observed Ph-negative( juvenile) forms of chronic myelogenous leukemia have similar symptoms, but differ in more severe and rapidly progressing course, the presence of a pronounced monocyte component. Characteristic of splenomegaly, extramedullary leukemia infiltrates.

Factors of unfavorable prognosis: the blast content in the peripheral blood is more than 1%, in the bone marrow - more than 5%;basophils and eosinophils( in total) in peripheral blood - more than 15%;increase spleen more than 6 cm below the edge arch;the content of platelets is more than 700x109 / l;age over 45;aberration of the karyotype( except Ph-chromosome

soma).The most important factors of the forecast are an increase in the number of blasts in the peripheral blood and splenomegaly. The criteria for remission for chronic myelogenous leukemia are given in Table 1.

Table Remission criteria for chronic myelogenous leukemia

Table Remission criteria for chronic myelogenous leukemia