STOP LEUKEMIA

Acute myeloid leukemia

Acute myeloid leukemias with multilinear dysplasia in residual normal sprouts of hemopoiesis are distinguished on the basis of certain morphological features, the presence of which sometimes makes it difficult to diagnose a specific variant of acute leukemia. In accordance with recent views in the classification indicates that the presence of multilinear dysplasia is a poor prognostic sign. A number of authors, including us, have shown that the presence of dysplasia does not in itself have a negative prognostic value, and a poor prognosis is determined by the frequent presence of unfavorable chromosomal aberrations in patients of this group. Most likely, this rubric will disappear from the classification in the future.

Rationally, in our opinion, the selection in a separate section of acute myeloid leukemia and myelodysplastic syndromes, the development of which can be associated with previous therapy, mainly with the use of alkylating drugs, topoisomerase II inhibitors and radiation therapy. These leukemias also have fairly well-defined biological features — often a period of myelodysplasia preceding the development of leukemia, often with characteristic or multiple chromosomal aberrations, often worse than de novo response to therapy and prognosis. In this group, in each case, when making a diagnosis, the notation is used in accordance with the FAB classification.

If acute myeloid leukemias do not belong to any of the listed groups, they are characterized in accordance with the FAB classification. It should be noted that in practice the classification of FAB is always used, and this must be recognized as rational, as it allows you to accurately determine which variant of acute myeloid leukemia is involved, and thus avoid erroneous conclusions in assessing the results obtained by different authors.

Myelodysplastic syndrome

Significant changes have been made in the classification of myelodysplastic syndromes compared with the FAB classification. Cases with the number of power cells of more than 20%, previously designated as RAIB-T (refractory anemia with an excess of blast at the stage of transformation into acute leukemia), are now considered as acute leukemia, which should be considered completely fair, given the further development of the disease in cases of with so many blast cells and, as a rule, the rapid emergence of all signs of acute leukemia.

It is fair to recognize the release of refractory cytopenia with dysplasia of two or more sprouts of hemopoiesis {refractory cytopenia with multilinear dysplasia). Hematologists are well aware that there are various variants of cytopenia with dysplasia or cases of multilinear dysplasia, but without anemia. Previously, they all had to be designated as refractory anemia.

The allocation of unclassifiable myelodysplastic syndrome is correct, since it is often in the group of myelodysplastic syndromes that there are often cases when, in the presence of obvious features of myelodysplasia, the disease for a very long time is difficult to attribute to a specific variant. A completely new is the allocation of myelo-dysplastic syndrome with an isolated deletion of the long arm of chromosome 5 – 5q- syndrome. In recent years, this syndrome has been considered as a special variant of myelodysplastic syndrome, characterized by significant anemia and at the same time a favorable long course. It is a more favorable prognosis than with other variants of myelodysplastic syndromes, and the absence of the need for intensive therapy serve as the basis for highlighting this option in a separate rubric.

In the rubric of acute myeloid leukemia, the WHO classification has made significant changes compared to the FAB classification, but it should be immediately emphasized that the FAB classification has also been preserved.

According to the WHO classification, all acute myeloid leukemias are divided into 5 categories based on the biological properties of the tumor: 1) with recurring chromosomal abnormalities; 2) with multilinear dysplasia; 3) acute leukemia and myelodysplastic syndromes, the development of which is associated with previous therapy; 4) acute leukemia, which cannot be characterized on the basis of any biological features; 5) acute leukemia of unclear linear affiliation (undifferentiated, bilinear and biphenotypic).

Acute leukemias with recurring chromosomal abnormalities are acute myeloblastic leukemia with t (8; 21), acute myeloid leukemia with eosinophilia in the bone marrow and aberrations of chromosome 16, acute promyelocytic leukemia with t (15; 17) and acute myeloid leukemia with aberrara leukemia with aberara leukemia with aberara leukemia with ab (15; 17) chromosomes 11-11q23.

All leukemias of this group are distinguished by certain biological features: often the characteristic morphology of tumor cells, which allows a diagnosis to be made on the basis of a morphological study and, in most cases, a predictable reaction to modern therapy. Isolation of this group of leukemias is important because they have certain approaches to therapy.
Translocation (15; 17) is pathognomonic for acute promyelocytic leukemia, in which the use of ATRA is necessary from the first days of treatment. This drug has fundamentally changed the prognosis of the disease. With modern therapy, the prognosis for leukemias with t (8; 21) and aberrations of chromosome 16 with eosinophilia in the bone marrow is generally favorable, but for leukemia with aberrations of chromosome 16, only with consolidation of remission with high doses of cytosar. The prognosis is much worse in the presence of changes in the llq23 region, therefore the detection of this aberration necessarily implies intensive therapy.

Thus, the biological characteristics of the leukemias of this group, as well as a specific reaction to therapy, justify the isolation of the leukemias of this group into a separate heading in the classification. At the same time, when establishing a diagnosis for a specific patient, each of the leukemias of this rubric is still characterized in accordance with the FAB classification.

Myeloproliferative Diseases

Among myeloproliferative diseases, “unclassifiable” is also indicated. This category includes diseases that have all the features of myeloproliferative, but without a sufficient number of signs that can be attributed to any specific nosological unit. The merit of the authors of the classification is in strict caution against making a diagnosis of myeloproliferative unclassifiable disease in those cases when all modern diagnostic methods that make it possible to accurately identify the diagnosis were not used. It is indicated that most often after some time, in cases initially diagnosed as unclassifiable, certain features of true polycythemia, or chronic idiopathic myelofibrosis, or essential thrombocythemia, appear.

In chronic myeloproliferative / myelodysplastic diseases, there are features of delayed maturation and dysplasia in any of the hematopoietic lines and / or ineffectiveness of hematopoiesis in this line. It seems to us absolutely correct to assign chronic myelomonocytic leukemia to this group, which was previously considered as one of the variants of myelodysplastic syndromes and which certainly has features of both myeloproliferative and myelodysplastic diseases. There is no doubt that the classification of juvenile myelomonocytic leukemia to this category is correct.

This group also contains a rare disease – atypical chronic myeloid leukemia, for which the term “subacute myeloid leukemia” was used long ago. The disease is characterized by hyperleukocytosis, the presence of young forms of granulocytes in the blood (promyelocytes, myelocytes, metamyelocytes), the absence of basophilia and the presence of signs of dysplasia in the cells of the granulocytic germ and sometimes also in the cells of the erythroid and / or megakaryocytic germ hemopoiesis. Chromosomal aberrations are common, but there are no specific ones among them, in particular, Ph (BCR-ABL) is not detected. The level of alkaline phosphatase in neutrophils can be any. Most likely, pathogenetic mechanisms of the development of this disease will be established in the future and it will be identified more specifically.

In this category also has unclassifiable myelodysplastic / myeloproliferative disease, which the authors designated as a disease having both laboratory features of one embodiment myelodysplastic syndrome and myeloproliferative process, such as thrombocytosis, or simultaneously features myeloproliferative and myelodysplastic processes which can not be attributed to any specific category . Chromosomal aberrations can occur, but are not specific to a particular disease.

It should be recognized that almost every hematologist meets with diseases that can not be attributed to any particular category. The merit of the authors of the classification is that they have designated this provision, although the term “unclassifiable” disease, even assigned to a specific group, cannot fully satisfy. It reflects the current state of science and the obscurity of the biological mechanisms underlying some clinical and morphological syndromes.

Chronic neutrophilic leukemia

Chronic neutrophilic leukemia differs in the blood picture from chronic myeloid leukemia by its lower leukocytosis and the absence of immature forms of myelopoiesis in the blood or by the presence of very small numbers of them. These signs are not enough for the differential diagnosis of these diseases, so the diagnosis of neutrophilic leukemia is made only on the basis of cytogenetic data. Previously, Ph (BCR-ABL) -negative cases and BCR-ABL-positive chronic myeloid leukemia with p230 protein production were ranked as chronic neutrophilic leukemia. In this classification, the diagnosis of chronic neutrophilic leukemia is left only for the BCR-ABL-non-affective variant; a disease with t (9; 22) and p230 protein production is considered as a variant of chronic myeloid leukemia. This seems to us to be absolutely fair and corresponding to the role of t (9; 22) in the pathogenesis of the disease.

In determining chronic eosinophilic leukemia and the hypereosinophilic syndrome, difficulties in differential diagnosis are emphasized. Currently, the hypereosinophilic syndrome includes a heterogeneous group of diseases characterized by persistent high eosinophilia of unknown origin. Appeared work, which showed that, at least in some cases, high eosinophilia occurs as a result of interstitial deletion of the long arm of chromosome 4 and the consequent formation of a chimeric gene with tyrosine kinase function. It is possible that such cases will be referred to as eosinophilic leukemia and the name “hypereosinophilic syndrome” will disappear, but now this term is used in all publications.

It should be recognized that this introduces a certain confusion, since reactive eosinophilia is sometimes described in practice under this term. At the same time, hypereosinophilic syndrome is a clearly defined symptom complex with a severe course and almost always an extremely poor prognosis. Cytogenetic analysis in cases of hypereosinophilia of unclear genesis is very important, since with eosinophilic syndrome with interstitial deletion of chromosome 4, Gleevec is effectively used.

Classification of hematopoietic and lymphoid tissue tumors. WHO

Work began in 1995. Initially, it was carried out by 10 national committees, which included more than 50 leading pathologists in the world. The classification is based on the same principles that were used as the basis for the REAL classification of lymphomas (Revised European-American Classification of Lymphoid Neoplasms): morphological (histological and cytological) studies, immunophenotyping, cytogenetic research and analysis of clinical data are necessary to establish the diagnosis. Thus, when creating the classification, the authors were based on the biological features of the tumor determined by modern methods.

As soon as the classification was formulated by pathologists, a committee was created to verify its clinical value, which included more than 40 leading oncologists and hematologists in the world. After their work in 1997 at a special meeting of clinicians and pathologists, all the disputed clinical issues were discussed and agreed upon. Only after an agreement was reached at this meeting, was the WHO classification finalized and published.

Thus, as a result of the involvement of many specialists in most countries, the WHO classification has become the first classification of hematological tumors that is currently accepted and used throughout the world. Nevertheless, there are controversial issues in the classification. In all likelihood, it will still be refined and changed.

In the WHO classification, all hematological neoplasms are divided into groups according to the blood line to which the cells constitute the morphological substrate of this tumor: tumors from myeloid cells, lymphoid cells, histiocytic / dendritic cells (histiocytosis) and mast cells (mastocytosis).
Tumors from lymphoid cells in accordance with this classification are discussed in detail in the manual, but here is the view of one of the well-known immunologists, prof. N. N. Tupitsyn on the value of this classification. At the same time, the section on tumors of myeloid cells, in our opinion, should be considered.

Tumors from myeloid cells are divided into 4 large groups:

1) chronic myeloproliferative diseases;
2) diseases that have features of both myeloproliferative diseases and myelodysplasias;
3) myelodysplastic syndromes;
4) acute myeloid leukemia.

All leukemias (leukemia) are divided into two types – acute and chronic. This division is due to the different ability of leukemias to grow and develop proliferating cells.

With acute leukemia, the development of cells is practically absent, a large number of immature cells accumulate in the blood at an early stage of development. This leads to the inhibition of normal hematopoiesis of all sprouts. Such signs are detected in the blood in more than 80% of cases.

Chronic leukemia produces a population of granulocyte cells that are growing, which gradually replace normal peripheral blood cells.

It should be noted that acute leukemia will never go to chronic and vice versa.

Lymphoblastic

All leukocytes in the human body are divided into 2 types – granulocyte and agranulocyte (granular and non-granular), these two groups, in turn, are divided into eosinophils, basophils, neutrophils (granulocyte), and lymphocytes (B- and T-type) and monocytes (agranulocyte). In the process of maturation and development (differentiation), all cells undergo several stages, the first of which is the blast stage (lymphoblasts). Because of the bone marrow involvement by the tumor, the lymphocytes do not have enough time to develop in order to fully perform their protective functions. For the most part, in acute lymphoblastic leukemia, B-lymphocytes (approximately 85% of cases) are responsible for the formation of antibodies in the body. There are two types of acute lymphoblastic leukemia (ALL): B-linear and T-linear, depending on the type of cells – lymphoid progenitors.

Clinical symptoms of acute lymphoblastic leukemia

Syndrome of intoxication – weakness, fever, malaise, weight loss. Fever may also be associated with the presence of a bacterial, viral, fungal or protozoal (less common) infection, especially in children with neutropenia (less than 1500 neutrophils per 1 μl).

Hyperplastic syndrome – an increase in all groups of peripheral lymph nodes. Infiltration of the liver and spleen leads to their increase, which can be manifested by pain in the abdomen. There may be pain and aches in the bones due to leukemia infiltration of the periosteum and articular capsule and a tumor increase in the volume of the bone marrow. At the same time, on radiographs, it is possible to detect changes characteristic of leukemia infiltration, especially in tubular bones, near large joints.

Anemic syndrome – pallor, weakness, tachycardia, hemorrhage of the oral mucosa, hemorrhagic syndrome on the skin, pallor. Weakness occurs as a result of anemia and intoxication.

Hemorrhagic syndrome is associated with both thrombocytopenia and intravascular thrombosis (especially with hyperleukocytosis) and leads to the appearance of petechiae, ecchymoses on the skin and mucous membranes, hemorrhages, melena, vomiting with blood.

In boys, an initial increase in the testicles (5-30% of cases of primary ALL) can be detected. These are painless, dense, one- or two-sided infiltrates. Especially often it happens with hyperleukocytosis and T-cell variant of ALL.

Respiratory disorders associated with enlarged lymph nodes of the mediastinum, which can lead to respiratory failure. This feature is characteristic of the T-linear ALL.

There may appear hemorrhages in the retina of the eye, edema of the optic nerve. At an ophthalmoscopy leukemic plaques on an eyeground can be found out.

Because of the greatly reduced immunity, any skin damage is the focus of infection, paronychia, panaritium, infected insect bites and injection marks may appear.

Quite rare complications can be kidney damage as a result of infiltration (clinical manifestations may be absent) and exudate pericarditis due to impaired lymph flow between the endocardium and the epicardium.

Acute

Acute leukemia is a form of cancer that develops very quickly and during which the altered leukocytes accumulate in the blood and bone marrow. Acute leukemia can be of several types: lymphoblastic leukemia, which occurs most often in children, and granulocytic leukemia, which can be found most often in adults.

In the first case of leukemia, the changed leukocytes are collected in the bone marrow or lymph nodes, and in the case of granulocyte leukemia, leukocytes accumulate in the bone marrow.

The causes of leukemia

The causes of leukemia are still unknown. There is an opinion according to which there are some factors that make the risk of leukemia higher. These are genetic disorders, problems with the immune system, the effects of radiation and some chemicals that suppress hematopoiesis.

Symptomatic of acute leukemia

When an acute leukemia occurs, a person experiences high fever, weakness in the body, and other symptoms that are similar to the symptoms of influenza. Lymph nodes, as well as the liver and spleen, are increasing. There is a pain in the bones. Blood is poorly drained, bruises appear from a weak touch. Bleeding provokes the appearance of red or purple spots on the skin. There are frequent infections, weakness is progressing.

Chronic

Chronic lymphocytic leukemia is an oncological disease of the lymphatic tissue, in which tumor lymphocytes accumulate in the peripheral blood, bone marrow and lymph nodes. Unlike acute leukemia, the tumor grows slowly enough, as a result of which hematopoiesis disorders develop only in the late stages of the disease.

Symptoms of chronic lymphocytic leukemia

• Weakness
• Enlargement of lymph nodes
• Heaviness in the abdomen (in the left hypochondrium)
• Inclination to infections
• Sweating
• Weight loss

Most often, the first symptom of chronic lymphocytic leukemia is an increase in the size of the lymph nodes. Due to the enlargement of the spleen, there may be a sensation of heaviness in the abdomen. Often, patients experience significant general weakness, lose weight, they have an increased incidence of infectious diseases. Symptoms develop gradually, for a long time. Approximately in 25% of cases, the disease is detected by accident when analyzing blood prescribed for another reason (medical examination, examination for non-hematological disease).

In order to diagnose chronic lymphocytic leukemia, the following studies should be carried out:

Medical examination

Clinical blood count with counting of leukocyte formula

The examination of the bone marrow makes it possible to reveal a picture of the lesion characteristic of this disease.

Immunophenotyping of bone marrow cells and peripheral blood reveals specific immunological markers characteristic of tumor cells in chronic lymphocytic leukemia.

Biopsy of the affected lymph node with its morphological and immunological examination.

Determining the level of β 2-microglobulin helps predict the course of the disease.

Cytogenetic analysis allows obtaining data on the characteristics of tumor cells, which in some cases have prognostic significance.

Determination of the level of immunoglobulins allows to determine how great the risk of development of infectious complications in this patient.

There are several approaches to determining the stages of chronic lymphocytic leukemia – the Rai, Binet system and the International Working Group on Chronic Lymphocytic Leukemia. All of them take into account the fact that the life expectancy of patients with chronic lymphocytic leukemia depends on the extent of the tumor (the number of affected groups of lymph nodes) and the degree of hemopoiesis in the bone marrow. Disturbance of bone marrow hematopoiesis, caused by tumor growth in the bone marrow, leads to the development of anemia (a decrease in the number of erythrocytes in the blood) and thrombocytopenia (decrease in the number of platelets). Determination of the stage of chronic lymphocytic leukemia allows to make a decision about the need to start treatment and choose the most suitable regimen for this patient.

Myeloblast

Acute myeloblastic leukemia (acute granulocytic leukemia, acute myelocytic leukemia) often occurs in adults, the subtype depends on the level of cell differentiation. In most cases, the myeloblastic clone of cells is derived from stem hemopoietic cells capable of multiple differentiation into colony-forming units of granulocytes, erythrocytes, macrophages or megakaryocytes; therefore, in most patients malignant clones do not show signs of lymphoid or erythroid sprouts AML are observed most often; has four variants (M0 – M3) mo and M1 – acute without cell differentiation
M2 – acute with differentiation of M3 cells – promyeloblast leukemia, characterized by the presence of abnormal promyelocytes with giant granules; often combined with ICE, due to the thromboplasty effect of granules, which casts doubt on the usefulness of heparin in therapy. The prognosis for M: is more favorable than for M0-M, myelomonoblast and monoblast leukemia (M4 and M5, respectively) are characterized by the predominance of non-erythroid cells like monoblast. M <and M5 constitute 5-10% of all cases of acute myeloblastic leukemia. A frequent sign is the formation of extraostestinal foci of hematopoiesis in the liver, spleen, gingiva and skin, hyperleukocytosis exceeding 50-100×109 / l. Sensitivity to therapy and survival is lower than in other variants of acute myeloblastic leukemias Erythromycosis (Mv). The variant of acute myeloblastic leukemia, accompanied by increased proliferation of erythroid progenitors; characterized by the presence of abnormal blast nucleus-containing red blood cells. Efficacy of treatment of erythroleukemia is similar to the results of therapy of other subtypes, or somewhat lower. Megacaryoblastic leukemia (M7) is a rare variant associated with bone marrow fibrosis (acute myelosclerosis). Poorly gives in to therapy. The outlook is unfavorable.

Promyelocytic

Acute promyelocytic leukemia (APL, AML M3, OPML) is a variant of acute myeloid leukemia, which is characterized by abnormal accumulation of one of myeloid cells – promyelocytes. In turn, promyelocytes (see the article “Hemopoiesis”) are the precursor cells of granulocytes arising at one of the stages of their maturation (myeloblasts – promyelocytes – myelocytes – granulocytes).

Frequency of occurrence

APL is about 10% of all cases of acute myeloid leukemia. Unlike many other variants of acute myelogenous leukemia, APL is often found not in the elderly, but in young adults: the average age of patients at the time of diagnosis is about 40 years. However, APL can occur at any age, including children.

Signs and Symptoms

Like other types of acute leukemia, APL is usually characterized by manifestations of anemia (fatigue, weakness, dyspnea) and thrombocytopenia, that is, a lack of platelets (increased bleeding, bruising and bruising). Lack of normal leukocytes leads to infections. In addition, with PAL, bleeding may be observed in addition to the syndrome of disseminated intravascular coagulation (ICD). This is the most formidable symptom of PLA.

As a rule, APL is characterized by a very rapid appearance and increase in symptoms.

Diagnostics

APL is diagnosed on the basis of morphological and cytochemical analysis of a bone marrow sample. Diagnostics necessarily involves the detection of a characteristic chromosomal translocation of t (15; 17) (sometimes other, much rarer translocations) during a standard cytogenetic or molecular-genetic (polymerase chain reaction) assay.

Myeloid

Acute myeloid (myelocytic, myelogenous, myeloblastic, myelomonocytic) leukemia is a life-threatening disease in which myelocytes (cells from which granulocytes normally develop) become malignant and quickly displace normal cells in the bone marrow. This type of leukemia occurs in people of all ages, but mainly in adults.

Symptoms

The first symptoms are usually due to the fact that the bone marrow is unable to produce a sufficient number of normal blood cells. There are weakness, shortness of breath, fever and bleeding, infections often develop. Other possible symptoms are headaches, vomiting, irritability, pain in the bones and joints.

Causes

The likelihood of developing acute myeloid leukemia increases in the event of exposure to large doses of radiation and the use of certain chemotherapy agents for malignant tumors.

Leukemia cells accumulate in the bone marrow, destroying and replacing healthy cells from which normal blood cells should be produced. Malignant cells enter the bloodstream and enter other organs, where they continue to grow and divide. They can form small tumors (chloromas) under the skin; penetration into other organs may be accompanied by the development of meningitis, anemia, hepatic and renal insufficiency and damage to other organs.