Chronic lymphatic leukemia

In clinical terms, chronic lymphocytic leukemia, promyelocytic leukemia and hairy cell leukemia are generally considered as separate morphological and clinical-pathological units requiring different therapeutic approaches.

Chronic lymphocytic leukemia, the most common form of hemoblastosis, is a cell-mediated tumor of the immunocompetent system. Leukemia cells with chronic lymphocytic leukemia come from a single precursor and are monoclonal proliferation. The cell substrate of the disease consists of morphologically mature lymphocytes, mostly B-lymphocytes( approximately 95%), less often T-lymphocytes. The peculiarity of lymphocytes in chronic lymphocytic leukemia is their functional inferiority, a violation of the mechanism of antibody formation, that

causes the occurrence of various infectious complications in patients.

Chronic lymphocytic leukemia is not homogeneous. According to morphological features, the following subtypes of B-chronic lymphocytic leukemia are distinguished: small-cell( typical, more than 90% of leukemia cells are represented by small lymphocytes);prolymphocytic lymphocytic( less than 90% of small lymphocytes, more than 10%, but less than 55% of

prolymphocytes );mixed-cell( less than 90% of small lymphocytes, more than 10% of large and less than 10% of prolymphocytes).In a number of patients, B-chronic lymphocytic leukemia can be transformed into other, more malignant lymphoproliferative diseases: Richter's syndrome( diffuse large cell, imunoblastic lymphoma)( in 3-10% of patients);prolymphocytic leukemia( in 5-10%);acute lymphocytic leukemia( 2%);Plasma cell leukemia, myeloma-type disease [Romanova AFet al., 1997].The T-cell phenotype is represented by a rare T-cell variant.

In clinical and prognostic terms, it is very important to establish the belonging of leukemic cells to T- or B-phenotypes, since T-cell forms of chronic lymphocytic leukemia have a more aggressive course and are difficult to treat.

The most typical variant of the course of chronic lymphocytic leukemia is leukemia( the number of leukocytes is from 10 to 150x109 / l).However, in a number of cases, chronic lymphocytic leukopenia, proven by sternal puncture, proceeds with leukopenia( 1.5-3x109 / L) from the beginning to the end of the disease. With the expanded picture of lymphocytic leukocyte, the lymphocyte content reaches 80% and even 99%( with a more severe course).The majority of cells are represented by mature lymphocytes, often their micro- and mesogeneration, but they can show prolymphocytes( 5-10%), rarely - single lymphoblasts. An increase in the content of these forms usually indicates an exacerbation of the process. A characteristic feature of chronic lymphocytic leukemia is the presence of cellular shadows in the blood smears( the shadow of Botkin-Gump-rechta);Reeder cells( lymphocytes having a kidney or bilabial nucleus) are also often found. Red blood in the initial stage of the disease suffers little, but with time, anemia develops, autoimmune hemolytic crises are possible associated with the formation of anti-erythrocyte antibodies. Thrombocytopenia usually occurs when massive lymphoid infiltration is detected in the red bone marrow. However, in a number of cases, thrombocytopenia occurs early, which is due to the same immunological mechanism as the development of hemolytic anemia and leukopenia. In the punctate of the red bone marrow, lymphocytes predominate, the granulocytes and erythronormoblasts content is sharply reduced. In severe cases, even from the very beginning of the disease, the bone marrow contains up to 50-60% of lymphocytes. In the later stages, as well as in the terminal phase of the disease, total lymphatic metaplasia of the red bone marrow is found( 95-98%).When autoimmune hemolytic anemia appears, the picture of the item may change, as the number of erythroid cells increases in response to haemolysis. According to the diagnostic value, the sternal puncture is superior to the biopsy and puncture of the lymph node, in which the nature of lymphoid tissue hyperplasia can not always be established. When

signs of tumor progression with the release of pathological cells from the control of cytotoxic drugs may not be observed throughout the disease. Terminal blast crisis is rare( in 1-4% of cases), more pronounced tumor growth of lymph nodes is noted( but this transition is comparatively rare in chronic lymphocytic leukemia).The terminal stage is characterized by infectious complications, exhaustion, immune haemorrhagic syndrome and anemia.

In the T-cell variant of chronic lymphocytic leukemia, leukemic lymphocytes have polymorphous ugly nuclei, coarse chromatin, in some cells large azurophilic granules are detected. Such cells in the cytochemical study are characterized by high activity of acid phosphatase, a-naphthylacetate esterase;on immunological parameters they most often have a phenotype CD4 +, CD8-, less often CD4 +, CD8 + and extremely rarely CD4-, CD8 +.The course of the disease is often rapidly progressive, with a possible transition to blast crisis, but it can also be benign.

Several classifications of chronic lymphocytic leukemia have been proposed for the stages of the development of the disease. In the RAI classification( 1975), the zero stage is isolated only with lymphocytosis in the blood and red bone marrow and the subsequent 4 stages, which reflect the spread of the process through the lymph nodes, spleen and liver. The latter stages include processes with cytopenia( anemia, thrombocytopenia) regardless of lymphatic organ infiltration.

RAI classification of chronic lymphocytic leukemia

■ Stage 0. Lymphocytosis in the peripheral blood more than 15x109 / L, in the bone marrow & gt; 40%.

■ Stage I. Stage 0 with enlarged lymph nodes.

■ Stage II.Stage 0 with increasing lymph nodes or without stage I with hepato- and / or splenomegaly.

■ Stage III.Stage 0 with an increase in lymph nodes or without stage I or II with anemia( Hb less than 110 g / l).

■ Stage IV.Stage 0 with or without stages I, II, III, with thrombopenia( platelets less than 100x109 / L).

According to the International System [Binet et al., 1981], chronic lymphoid goats are divided into stages A, B, and C. The first two stages correspond to the process spread over three( A) and more( B) lymphatic fields - the lymph nodes of all peripheral groups, spleen, liver, and the third( C) - the process with cytopenia( anemia, thrombocytopenia).

International classification of chronic lymphocytic leukemia

A. Lymphocytosis in peripheral blood more than 4х109 / l, in red bone marrow - more than 40%.Hb 100 g / l, platelets more than 100,0х109 / l;spread of the process - up to two regions of enlarged lymph nodes( cervical, axillary, inguinal, liver, spleen).

B. Hb more than 100 g / l, platelets more than 100x109 / l, the spread of the process - more than three areas of enlarged lymph nodes.

C. Hb is less than 100 g / l and / or platelets of less than 100.0 × 109 / L, regardless of regions of enlarged lymph nodes.

Fig. Stem cell diseases, their interrelations and possible directions of transformation

Fig. Stem cell diseases, their interrelations and possible directions of transformation

Prolymphocytic leukemia in peripheral blood and bone marrow punctate is dominated by( more than 55%) prolymphocytes. Pathological cells in 75-80% of patients have a B-cell phenotype, which in their immunological characteristics are more mature lymphoid elements than lymphocytes with typical B-cell chronic lymphocytic leukemia. In 20-25% of patients, the cells have a T-cell phenotype, in such cases the disease proceeds more severely, with pronounced leukocytosis, progresses rapidly, therapy is not very effective.