Acute leukemias

General principles for the diagnosis of acute leukemia

Experience shows, in the early stages of leukemia clinical manifestations are absent: patients feel perfectly healthy until ubiquitous tumor cells of the hematopoietic system, to the development of organ dysfunction due to tumor growths.

The diagnosis of acute leukemia It may only be set to detect surely morfologicheski- blastic cancer cells in blood and bone marrow. Any specific external signs, inherent in the initial period of acute leukemia, can not be identified.

Hematologic picture of acute leukemia can be twofold. When the output of blast cells in the blood leukogram determined characteristic pattern of acute leukemia: the presence of both the young - blast - cells and mature granulocytes, monotsitov, lymphocytes. If the blood smear, and even found promyelocytes and myelocytes, their percentage in acute leukemia is low and the picture of failure in leukogram between young and mature cells preserved. If the blasts have not yet gained the ability to recover from the bone marrow into the blood, but it has already led to some disturbances in the body, so, their content in the bone marrow rather high. In the blood leukopenia, anemia, platelet- or pancytopenia.

In all cases, re-detectable incomprehensible cytopenia be compulsory study of bone marrow. In acute leukemia almost always in the presence of blood in the bone marrow cytopenia contains tens of percent blast cells. The exception to this rule may be rare cases of prolonged onset of acute leukemia, when blast cells have a pronounced effect tsitopenichesky, but had not yet provide significant growths; just the appearance from the beginning of acute leukemia autoimmune cytopenia (cytolytic autoimmune conditions can complicate the course of any leukemia) the percentage of blast cells in the bone marrow can be small.

Certain difficulties in the diagnosis of acute leukemia is the so-called Acute leukemia maloprotsentnыy, characterized by low content of blast cells in the blood (less than 10-20 %) and sometimes - even smaller blastosis bone marrow. Diagnosis of acute leukemia is relatively rare, occurs mainly in the elderly, not so complicated, since under no conditions jet blast cells in peripheral blood in an amount of several percent is not met.

A typical diagnostic feature of acute leukemia is the classical structure of the nucleus of blast cells - pale chromatin, tonkosetchataya, with a uniform color and size of the chromatin threads.

However, the leukemic blasts are very diverse, even in the same patient in the same smear.

Describe a typical form of blasts occur relatively infrequently, the bulk of the tumor cells comprise any elements with oiled chromatin structure, but with the cytoplasm, similar blasts typical of this preparation, or grossly, irregular chromatin network, but with nucleoli etc.. P. All such cells counting myelogram or hemogram can be categorized blasts only, when these blasts are tens of percent. In all other cases, atypical blasts These include the impossible - they must describe in detail, without giving them names.

Of particular importance is correct assessment of the nature of the cells in the diagnosis of acute leukemia remission, which is characterized 5 % blasts or less. It is very important to focus on the content of a smear myelokaryocytes: with a small amount of cells (eg, when agranulocytosis) may dominate the young lymphoid cells with narrow cytoplasm, sometimes with nucleoli (- especially in children), but with a homogeneous structure of chromatin. This - progenitors. They should rank as a category of lymphoid cells. Glybchataya structure of normal lymphocytes is not typical for them. Detection of bone marrow 20-30 % krugloyadernyh cells, reminding blasts, usually regarded as the emergence of atypical, requiring precise morphological description of the cellular elements.

The use of cytotoxic drugs and prednisolone before the diagnosis is unacceptable, because it can lead to erroneous diagnosis of acute leukemia in cases of infectious mononucleosis or transferred immune hemolytic crisis.

Sometimes Acute leukemia myeloblastnыy It begins to increase the blood levels of all young cells: and blast, and promyelocytic, and myelocytes, and metamyelocytes and t. d.

Differential diagnosis of blast crisis of chronic myeloid leukemia and acute myeloid leukemia It does not have much practical significance, therapy since in both cases is the same.

Significant the difficulties for the diagnosis can be acute immune hemolysis, which is accompanied by a sharp increase in the content in the bone marrow reticular cells (10-20 %). These cells are sometimes mistaken for blasts, although they always have rough chromatin structure, large blue nucleoli; Besides, revealed a sharp increase in the number of bone marrow erythrokaryocytes, and in the blood - high reticulocytosis.

Possible and this situation, when along with nevyskim percentage of blast cells in the bone marrow punctate has broken a number of granulocyte maturation level myelocytes or of promyelocytes, more common in immune neutropenia or agranulocytosis. The difficulty in diagnosis is particularly high in the case, If there are no blood tests blasts, No thrombocytopenia, and blast cells in the bone marrow punctate no different atypia, and the ratio of nucleus and cytoplasm, lack of graininess in the cytoplasm resemble normal progenitor cells to form Blasta. In such doubtful cases the biopsy shows, for detection in acute leukemia blast cells proliferative.

Given the difficulty in establishing the diagnosis of acute leukemia are relatively rare and should not give rise to unlimited puncture bone marrow, eg, in patients with transient leukopenia after flu, leukopenia stable against the background of hyperthyroidism or cirrhosis, and so. P.

There may be situations, when in connection with cytopenia diagnosis fails, Although acute leukemia and is suspected. In these cases, we have to repeat all the studies in a few weeks, months. Some of belated diagnoses should be classified by reducing blood tests, when with anemia of unknown character is not counted the number of platelets, and reticulocytes.

In early acute leukemia there may be a normochromic or slightly hyperchromic anemia - a color index reaches 1.2-1.3. Especially pronounced tendency to hyperchromia in acute erythromyelosis. Among the red blood cells at the same time a significant number of macrocytes. Platelet counts in most cases either reduced, Either normal. Very rarely there are cases of acute leukemia (apparently, nelimfoblastnyh) with hyperthrombocytosis, reaches several million 1 l. At the same time found an unusual shape and platelets, large blue cytoplasm.

On the issue of the initial manifestations of acute leukemia, it must be emphasized, In all observed cases, where possible to detect aneuploid clone, or clone with some defect in the karyotype, through a particular period of time it is always the clone becomes the basis blastic leukemia.

Upon detection of abnormal cell clone in patients with cytopenia should diagnose early manifestations of acute leukemia. In the case of a normal karyotype put syndromological diagnosis:

• aplastic syndrome (Aplastic anemia is a focal hyperplasia in the bone marrow undifferentiated elements);
• thrombotic syndrome;
• granulozitopenia of unknown origin, etc.. d.

One indication of the future may be acute leukemia unmotivated monocytosis, which, unlike the chronic monocytic leukemia is not accompanied by polymorphonuclear cell pronounced hyperplasia of cells in the bone marrow trepanate. The nature of the monocytosis, often appearing several years before the development of leukemia, not clear. Since in such cases the protracted monocytosis then develops myelomonoblastic myeloid or acute leukemia, or acute erythroleukemia in the background preceding neutropenia, You can think of, Monocytes in these cases are not leukemic, and arise from regulatory violations monocytopoiesis because leukemic suppression neytrofilopoeza (similarly reactive monocytosis develops in hereditary neutropenia).

The number of leukocytes in the beginning of the process often reduced, but at the same time, there are cases, when at the first clinical manifestations of notes and high leukocytosis with a predominance of blasts in hemogram.

Often in acute leukemia in the blood are found isolated erythrokaryocytes, that have a significant differential diagnostic value: they are absent in the reactive states (excluding hemolysis, leukemoid response to cancer), infectious mononucleosis.

In some, very rare cases, there polycythemia (in a 5T 1 l), preceding the developed picture of acute leukemia. If the output erythrokaryocytes, as well as the appearance of blood myelocytes and promyelocytes, It may be linked to disruption of the structure of the bone marrow, growth of blasts (A similar picture is the blood and cancer metastases in the bone marrow), the macrocytosis, hyperchromia erythrocytes, as well as the often observed phenomenon megaloblastoidnosti erythrokaryocytes, probably, associated with the deficiency of red progenitor cell number, which are already being leukemia, retain some ability to differentiate.

ESR in acute leukemia can be somewhat increased, sometimes significantly increased or normal.

This picture of the blood is related to the primary process, caused by leukemia, and significantly altered by cytostatic therapy; Besides, it varies in different forms of acute leukemia.

Stages of acute leukemia

Classification of stages of acute leukemia pursues purely practical purposes: determining therapeutic tactics and prognosis assessment.

Currently, due to the success of cytostatic therapy of leukemia clear boundaries define all stages of the process treatment policy. In some cases we are talking about the use of powerful systems cytostatics, to eradicate leukemia, in the other - on the prevention of relapse using long, but a weak cytostatic effects, third, on the Elimination of local recurrence. But very often the struggle for the eradication of tumor growth becomes impossible, and the doctor has to be limited to maintaining the achieved partial response.

These fundamental differences in treatment strategies formed the basis Classification of stages of acute leukemia, which can be represented as follows:: initial stage, the first attack, or advanced stages of the disease, complete remission, recovery, partial remission, relapse, indicating its number and location, end stage.

The initial stage of acute leukemia

Accumulated to date information about the initial phase of acute leukemia is so scarce, which give a specific definition of it is not yet possible. Most often it is a retrospective assessment, where, eg, limited swelling of the blast cells (in limfatičeskom uzle, skin, meninges and t. P.) under normal part of the bone marrow gives further colonization of his overbearing and out of their cells in the blood. However, in the case of isolated nature lymphoblastic tumors of the lymph nodes in children seems the most appropriate treatment for them in the usual way for lymphoblastic leukemia.

Advanced stages of acute leukemia

Advanced stages of the disease is characterized by a pronounced inhibition of normal hematopoiesis, high blastosis bone marrow (except maloprotsentnogo leukemia). This stage therapeutic and prognostic point of view is not uniform:

• the first attack on fundamentally different leukemia recurrence, develop on the background of cytostatic therapy;
• each subsequent relapse prognostically more dangerous, than previous, and generally requires a new combination of cytostatics (although it may be returned to the sensitivity of leukemia cells previously used cytostatics);
• in turn, remission can be total or partial.

Complete remission in acute leukemia

It includes a complete remission status, where In bone marrow revealed no more 5 % blast cells, and the total number of cells and lymphoid blast does not exceed 40%, wherein in the peripheral blood blast cells lacking, the blood close to normal, clinical signs of leukemic cell proliferation in the liver, spleen and other organs were observed (for lymphoblastic acute leukemia remission mandatory criterion of completeness is the normal composition of the cerebrospinal fluid).

Recovery in acute leukemia

Recovery from acute leukemia It is considered to be a state of complete remission for five years or more.

Partial remission in acute leukemia

Partial remission It is a fairly diverse group of states, which are characterized by distinct improvement in hematologic (significant reduction in the percentage of blast cells in the bone marrow by increasing the proportion of normal cells, combined with the improvement of the blood), or disappearance of blast cells from the blood while retaining blastosis bone marrow, or decreasing the number of blast cells in the cerebrospinal fluid with elimination of clinical symptoms neuroleukemia, or some suppression of proliferation of leukemic foci other is bone marrow and T. P.

Recurrence of acute leukemia

Recurrence of acute leukemia can be bone marrow (the emergence of more 5 % blast cells in a punctate) or local - Vnekostnomozgovym with any localization leukemic infiltration.

Leukemic and aleukemic phase of acute leukemia

From a purely hematological position should allocate leukemic (yield blasts in blood) and aleukemic (without their appearance in the blood) phase of acute leukemia.

Regardless of the cause, caused the appearance of remission, hematology and clinical picture of the disease is characterized by the dynamics of legitimate. In the presence of the patient's leukemic phase of the disease, in the case of an effective therapy of blood blast cells often lose their characteristic structural nuclear chromatin and become limfotsitopodobnye. Sometimes this transformation takes 1-2 days, often - several days.

If leukemia is accompanied by intoxication, hemorrhagic syndrome, then, despite the absence of more mature growth of normal blood cells, being patient with remission for offenses is improved and bleeding is reduced.

In the future, the number of white blood cells is reduced (due to the disappearance of priority abnormal cells), on the steps of varying degree or leukopenia, and then marked increase in the number of mature normal cells. When leukemic phase of the disease stage of pancytopenia before restoring shelter creation is practically mandatory.

The real fullness of remission can not estimate. Biopsies of internal organs, the results of pathological studies (when death from infectious complications), undertaken over a splenectomy, or for other reasons, show, that proliferative undifferentiated blast cells in the spleen, kidney, lymph nodes are preserved in patients in remission. Chromosomal analysis of the bone marrow also suggests the possibility for long-term preservation (2 year) remission 0.5-1 % aneuploid cells (same, that were and remission), though staunchly remains normal myelogram. Microscopy punctate allows in some cases to identify among individual blasts, certainly abnormal cells, which is less than 1 % and do not interfere to assess the situation as a complete remission.

Sometimes he used the term "clinical remission", which is characterized by improving the general condition of the patient, the disappearance of septic complications, hemorrhages when no significant changes in hematology cal picture of the disease. In these cases, to speak of clinical improvement without remission.

Terminal exacerbate leukemia often preceded by a partial remission. Where, When the abnormal cells become less sensitive to all applicable cytostatics, than normal bone marrow progenitor cells, t. it is. when under the influence of cytostatics granulocytopenia or thrombocytopenia increases faster, than the content decreases blasts, the doctor has to stop trying to obtain a complete remission and go to treatments, aimed at achieving a partial positive effect.

End-stage acute leukemia

End-stage acute leukemia at first glance does not have certain features, However, monitoring of patients shows, that the development of leukemia inevitably there comes a point, when all cytostatics not only ineffective, but their background process progresses: growing granulocytes- and thrombocytopenia, appear foci of necrosis on the mucous membranes, spontaneous hemorrhage.

By the manifestations of end-stage concerns the emergence of foci of sarcomatous growth in the skin, miokarde, kidney.

But decisive role in the development of end-stage belongs primarily complete inhibition of normal hematopoiesis germs, instead of internal organ involvement, which can take place before and not always mean treatment failure (eg, acute lymphoblastic leukemia-specific infiltration of the meninges, or the testicles are usually eliminated in the appointment of cytostatics, gamma-therapy or, Although conserved, but for a long time does not lead to the generalization of the process and the patient's death).

The concept of the terminal phase is conditional, it only reflects the current level of therapeutic opportunities and incurable stage of tumor progression of leukemia.

Thus, the diagnosis of acute leukemia indicating advanced disease formulated as follows: acute myelogenous (lymphoblastic, promyelocytic etc.. d.) leukemia (complete remission; first relapse - or bone marrow infiltration with local eggs; partial remission - neuroleukemia the normalization of bone marrow; end stage), aleykemicheskaya phase.

Any of the forms of acute leukemia can occur with deep primary cytopenia. Isolation of primary cytopenia in a separate step improperly, since in all cases we are talking about the process unfolded, but proceeding with a pronounced inhibition of normal hematopoiesis. However, therapeutic products, this phenomenon deserves attention, since in some cases the primary cytopenia is expressed as, cytostatic therapy that all formal criteria seems contraindicated, Although only one and may lead to remission.