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  • Diagnosis of acute leukemia

    For the diagnosis of acute leukemia, a clear morphological verification is necessary - the detection of undoubted blast cells in the red bone marrow. For , the diagnosis of acute leukemia is certainly necessary to establish the classical structure of the nucleus of blast cells( gently chromatin - thin-stranded with a uniform caliber and coloration of chromatin strands).

    Changes in peripheral blood. Valuable information for all hemoblastic diseases primarily gives a cytomorphological study of peripheral blood cells. In acute leukemia, all elements of hematopoiesis have profound pathological changes. In most cases of acute leukemia, anemia develops. Anemia is normochromic, hyperchromic, less often hypochromic and deepens as the disease progresses( Hb concentration decreases to 60-20 g / l, the number of erythrocytes is 1.5-1.0 x 1012 / L).Another characteristic sign of acute leukemia is thrombocytopenia( often below the critical level).During the disease and under the influence of treatment, the content of platelets undergoes cyclic fluctuations: at the onset of the disease it is often normal, with exacerbation and progression decreases, during the period of remission increases. The total number of leukocytes varies widely - from leukopenia to 100-300x109 / l( higher rates are rarely recorded).Leukocytosis at the time of primary diagnosis of acute leukemia is observed in less than a third of cases, it is usually accompanied by a high content of blast cells [Vladimirskaya E.B.et al., 1998].Significantly more often in a primary blood test, the number of white blood cells is normal or they show leukopenia with relative lymphocytosis. Usually among the lymphoid elements it is possible to identify blast cells, but there are cases when typical blast cells in the blood are absent. Leukopenic forms account for 40-50% of all cases of acute leukemia, while the number of neutrophils can decrease to a catastrophic level( 0.2-0.3x109 / L).The development of cytopenia( granulocytopenia, anemia, thrombocytopenia) in acute leukemia is a consequence of the inherent oppression of normal hematopoiesis. A certain value in the occurrence of cytopenia has also an autoimmune cytolytic mechanism, which can complicate the course of any leukemia.

    Beginning as a leukopenic, acute leukemia often maintains this trend throughout the disease. Sometimes leukopenia is replaced by leukocytosis( in untreated patients as the process progresses), and vice versa( for example, under the influence of cytostatic therapy).For acute leukemia is characterized by the so-called leukemia gap: the absence of transition elements between the cells that make up the morphological substrate of the disease, and mature leukocytes.

    Leukemia, in which peripheral blood is detected pathological blast cells are called leukemia, and leukemia( or leukemia) with no blast cells in the blood - aleukemic.

    Changes in the red marrow. The study of red bone marrow is an obligatory study in the diagnosis of acute leukemia, including in those cases when the diagnosis of acute leukemia does not raise any doubts after the study of peripheral blood [Vladimirskaya E.B.et al., 1998].This is due to the basic rule of oncology - only the study of the substrate of the tumor gives the basis for the diagnosis.

    Blast forms( more than 60%) usually prevail in the red bone marrow during the manifestation of acute leukemia, as a rule, sharp inhibition of the erythrocyte sprout and a decrease in the number of megakaryocytes with a degenerate shift in the megakaryocytegram.

    Diagnosis of the cytopenic forms of leukemia is difficult, as the blood picture often resembles that of aplastic anemia and agranulocytosis: anemia, leukopenia( granulocytopenia and relative lim-phocytosis).Bone puncture usually resolves diagnostic issues. The exception is M7( megakaryoblastic) variant of acute leukemia, in which the pronounced development of bone marrow fibrosis does not allow to receive a full punctate( cell count is low, a significant admixture of peripheral blood).An important diagnostic method for this form of acute leukemia is trepanobiopsy of the bone. Histological examination of bone sections allows to establish pronounced blastic hyperplasia of red bone marrow.

    The diagnosis of acute leukemia can be made in the following cases.

    ■ Blast cells make up at least 30% of all cellular elements of the red bone marrow;

    ■ When erythrocaryocytes predominate in the bone marrow( more than 50%), blasts make up at least 30% of non-erythroid cells( with acute erythromyelosis).

    ■ Morphologically characteristic hypergranular atypical promyelocytes( acute promyelocytic leukemia) predominate in the bone marrow.

    In other, more rare cases, the detection of 5-30% of myeloid blasts among all bone marrow cells allows talking about the diagnosis of myelodysplastic syndrome, namely, refractory anemia with increased blast content( previously this form of myelodysplastic syndrome was called low-percentage acute leukemia).When establishing the lymphoid nature of blast cells, it is necessary to exclude malignant lim-phoma during the generalization stage. At present, the FAB classification of the myelodysplastic syndrome is used, which is shown in the table.

    Table FAB classification of the myelodysplastic syndrome [Jonts SL, 2000]

    Table FAB classification of the myelodysplastic syndrome [Jonts SL, 2000]

    Trepanobiopsy is necessary for differential diagnosisacute leukemia and lymphosarcoma. With ALL, infiltration with blast cells is diffuse, for lymphosarcoma the nesting of blast cells is more characteristic against a background of preserved hematopoietic tissue.

    To identify one or another form of leukemia when an increased blast cells content in the red bone marrow can be used, the algorithm for diagnosing acute myeloid leukemia and myelo-dysplastic syndrome, proposed by the scientists of the FAB group.

    Blast cells in acute leukemia, despite the tumor nature, retain the known morphological and cytochemical features of similarity with their normal counterparts. The classification of non-lymphoid leukemias is based on this principle. The establishment of a cytomorphological variant of acute leukemia is of great importance in the conduct of differentiated chemotherapy.

    Fig. Algorithm for the diagnosis of acute myeloid leukemias( AML) and myelodysplastic syndrome( MDS)

    Fig. Algorithm for the diagnosis of acute myeloid leukemias( AML) and myelodysplastic syndrome( MDS)

    Changes in cerebrospinal fluid. Lumbar puncture in acute leukemia is an obligatory diagnostic procedure. The purpose of this manipulation is early detection, prevention and treatment of neuroleukemia. With the manifestation of acute leukemia, neuroleukemia is detected in 3-5% of cases, the detection of this syndrome immediately allows the patient to be referred to a group of high risk, which determines the choice of the appropriate treatment program. The presence of high concentration of protein in the cerebrospinal fluid, cytosis of more than 5 cells in 1 μl suggests neuroleukemia. For the final diagnosis, smears are prepared and morphological, cytochemical and immunocytological studies of the cells are carried out.