Acute megakaryocytic leukemia. Megakaryocytic leukemia
UDC 616.411-003.972
E.Z. GABBASOVA,AND. S. SHERIAZDAN, G.A. SABYRBAEVA,
M.K. ZHUMAKHANOVA,
Kazakh National Medical University named after. S.D. Asfendiyarova
Department of Internship and Residency in Therapy No. 3
This article presents clinical case rare variant acute leukemia– megakaryocytic. The clinical picture, morphological examination data andAndimmunophenotyping bone marrow. Features of the disease in the presented observation were the presence of thrombophilic episodes and unfavorable outcome.
Key words: rare variant, acute leukemia, acute megakaryocytic leukemia, M7, clinical case.
Acute megakaryocytic leukemia(AML, AML M7, according to FAB classification) - a variant of acute myeloid leukemia, in which blast cells, which form the basis of the disease, are mainly represented megakaryoblasts(these are the precursor cells of megakaryocytes, from which, in turn, platelets are formed).
AML is a very rare variant of acute myeloid leukemia. Its exact proportion among all cases of acute myeloid leukemia, according to different estimates, is 3-10% in children (most often younger and with Down syndrome), and in adults only 1-2%. The age distribution of AML has two peaks: one among young children (up to 3 years), the other among older adults.
AML is characterized by the presence in the bone marrow and blood of megakaryoblasts (cells with a blastic but hyperchromatic nucleus, narrow cytoplasm with filamentous outgrowths), as well as undifferentiated blasts. Often, ugly megakaryocytes and fragments of their nuclei are found in the blood and bone marrow. Thrombocytosis is characteristic (more than 100 - 104 in 1 μl), but thrombocytopenia may also be present. Immunophenotype of the pathological population: HLADR-/, CD33/, CD34, CD41, CD61. AML is difficult to treat, so the prognosis is usually unfavorable.
Considering the rarity of this variant of leukemia and the difficulties of its differential diagnosis, it seems appropriate to us to present our own observation of acute megakaryocytic leukemia.
Clinical observation
Patient M., 55 years old, in August 2011 was hospitalized in the hematology department of City Clinical Hospital No. 7 in Almaty. From the anamnesis it is known that since June of the same year, he was periodically bothered by nosebleeds, pain in the left hypochondrium, and began to notice increasing weakness, sweating, and weight loss. Subsequently, the patient was observed for thromboembolism pulmonary artery, due to which he was hospitalized in the hospital. During the examination: the hemogram revealed severe normochromic anemia, leukocytosis up to 62 thousand with neutrophilia, hyperthrombocytosis up to 1912x10 9 l, ESR-65 mm/hour; in the coagulogram: hypocoagulation, hyperfibrinogenemia, thrombinemia. After the conservative treatment and stabilization general condition the patient was referred for further examination and treatment to a hematologist.
Status on admission: severe condition, Karnofsky index 70%. Skin pale, hemorrhagic ecchymoses at injection sites. Asthenic, low nutrition. Zev is calm. Peripheral lymph nodes are not enlarged. T-36.6S.
From the outside respiratory system: chest of normal shape, percussion - clear pulmonary sound. On auscultation, weakened vesicular breathing, silent fine rales in lower sections. ChD-24 per min. Heart sounds are muffled, the rhythm is correct. Blood pressure 120/70mmHg. Pulse-83 per minute. The tongue is moist and clean. The abdomen is soft and painless. Liver +3 cm from under the edge of the costal arch, soft-elastic consistency, painless. The spleen is not palpable. The chair is decorated, in regular color. Urination is free and painless. Diuresis is adequate. The effleurage symptom is negative on both sides. There is no peripheral edema.
Peripheral blood analysis: hemoglobin -80 g/l, erythrocytes - 2.5x10 12 /l, platelets - 2000x10 9 /l, leukocytes - 72x10 9 /l, blastemia - 12%.
Morphological research bone marrow: blasts make up 60.6%. Blast cells are polymorphic. Cells vary in size, and both macro- and mesoforms are found. The outlines of the cells are irregular. The nuclear-cytoplasmic ratio is moderate. The nucleus is round, with a fine mesh chromatin structure. The kernel structure is rough. The cytoplasm is basophilic, granular, and has the appearance of a narrow rim. The contours of the cells are uneven, with processes of the cytoplasm and the formation of “blue” plates. Many megakaryocytes of an ugly shape and fragments of their nuclei in the field of view. When assessing the residual germs of hematopoiesis, attention is drawn to the pronounced dysplasia of elements of the granulocytic and erythroid series.
Immunophenotyping of bone marrow cells revealed a pathological population of progenitor cells with a phenotype characteristic of megakaryocytic leukemia: HLADR-/, CD33/, CD34, CD41.
Based on the above studies, according to the FAB classification criteria, a diagnosis of AML M-7, a megakaryocytic variant of acute leukemia, was established. Two standard courses of cytostatic therapy were carried out according to the “7+3” scheme (cytosar, rubomycin). Soon the patient developed acute thrombosis inferior vena cava and was carried out surgical treatment: through the skin, through the jugular implantation of a permanent cava filter into the infrarenal part of the inferior vena cava.
There was no expected effect from the PCT courses. Symptoms of intoxication increased. Last hospitalization according to emergency indications with pronounced symptoms of tumor intoxication, multiple organ failure, leukemic infiltration internal organs. The patient died 6 months after diagnosis from acute cardiovascular failure due to progression of the underlying disease. The autopsy was not performed according to the wishes of the relatives for religious reasons.
Thus, given the general rarity of acute megakaryocytic leukemia in adult patients, the presented observation is interesting in that it concerns a patient who, at the age of 55 years, was diagnosed with acute megakaryocytic leukemia, against the background of which episodes of thrombophilic conditions were repeatedly noted.
REFERENCES
1 Jaffe E. S., Harris N. L., Stein H., Vardiman J. W. (eds.). World Health Organization Classification of Tumors. //Pathology and Genetics of Tumors of haematopoietic and lymphoid tissues. Lyon: IARC, 2001.
2 Lowenberg B., Downing J. R., Burnett A. Acute myeloid leukemia // N. Engl. J. Med. – 1999. – R. 341.
3 Duchayne E., Fenneteau O., Pages M. P. et al. Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Francais d’Haematologie Cellulaire (GFHC) // Leuk. Lymphoma. -2003.- 44(1).
4 Abdulkadyrov K.M. Hematology // Newest reference book. – St. Petersburg, 2004
E.Z. GABBASOVA, Zh.S. SHERIYAZDAN, G.A. SABYRBAEVA,
Zh.I. BORANBAEVA, U.N. ZHIENBEKOVA,M.K. ZHUMAKHANOVA,
J.S. KALBASOVA, A.A. SEYTKABYLOVA
ZHEDEL MEGAKARYOCYTELS LEUKEMIA – LEUKOZDYҢ SIREK NUSKASY (OZINDIK BAKYLAU)
Tү yin: Atalgan makalada zhedel leukozdyn sirek nuskasy – megakaryocytes leukozdyn klinikalyk zhagdayy korsetilgen. Klinikalyk korіnіsі, morphologiyak zertteu zhane suyek kemіgіn immunophenotypteu malimetteri sipattalgan. Korsetilgen baqylauda was aurudyn ereksheligi thrombophilialyk episodetar zhane kolaysyz natizhe bolyp tabylady.
Tү withө zder: sirek nuska, zhedel leukemia, zhedel megakaryocytarly leukemia, M7, klinikalyk zhagday.
E.Z. GABBASSOVA, ZH. S. SHERIYAZDAN, G.A. SABYRBAYEVA,
J.I. BORANBAEVA, U.N. ZHIENBEKOVA, M.K. ZHUMAHANOVA,
ZH.S. KALBASOVA,A.A. SEYTKABYLOVA
ACUTE MEGAKARYOCYTIC LEUKEMIA – A RARE VARIANT OF LEUKEMIA (OWN OBSERVATION)
Resume: This article presents a case report of a rare variant of acute leukemia - megakaryocyte. We describe the clinical picture, these morphological studies and immunophenotyping bone marrow. Feature of the disease in the present observations were the presence of thrombophilic episodes and poor outcome.
Keywords: rare variant, acute leukemia, acute megakaryocytic leukemia, M7, clinical case.
Acute megakaryocytic leukemia (acute megakaryoblastic leukemia, AML, AML M7) - a variant of acute myeloid leukemia, in which blast cells, which form the basis of the disease, are mainly represented megakaryoblasts(these are the precursor cells of megakaryocytes, from which, in turn, platelets are formed).
Incidence and risk factors
AML is a rare variant of acute myeloid leukemia. Its exact proportion among all cases of acute myeloid leukemia, according to various estimates, is 3-10% in children (most often younger) and 1-2% in adults. However, among young children with Down syndrome, it is, on the contrary, the most common type of acute myeloid leukemia.
The age distribution of AML has two peaks: one among young children (up to 3 years), the other among older adults.
Occasionally, AML develops from a preexisting myelodysplastic syndrome.
Signs and symptoms
Like other types of acute leukemia, AML is usually characterized by symptoms of anemia (fatigue, weakness, pallor, shortness of breath) and thrombocytopenia, that is, a lack of platelets (increased bleeding, bruising and bleeding). Resistance to infections is reduced.
Common in AML myelofibrosis(myelosclerosis) – the process of replacing bone marrow with connective tissue. It also leads to anemia and thrombocytopenia and plays a role in the appearance of other symptoms: enlarged spleen (more often in children) and liver, bone pain, etc. In addition, myelofibrosis makes it difficult to take a bone marrow sample for diagnosis - so, a bone marrow puncture may be ineffective .
Diagnostics
The diagnosis of AML is usually made on the basis of morphological analysis of a bone marrow sample (detection of a sufficient number of megakaryoblasts - megakaryocyte precursor cells). The diagnosis is confirmed by immunophenotyping and cytochemical analysis. Cytogenetic analysis is used to determine chromosomal translocations; for example, in AML, the t(1;22) translocation is often encountered.
Treatment
In the treatment of AML, like most other types of acute myeloid leukemia, cytarabine and chemotherapy drugs of the anthracycline group (daunorubicin, idarubicin, mitoxantrone) are used. Other drugs are also used.
In force high probability relapse in AML, many patients (except for patients with Down syndrome) after achieving the first remission are recommended to undergo allogeneic bone marrow transplantation, although it is not a guarantee against relapse.
Forecast
AML is one of the most malignant variants of acute myeloid leukemia. More than half of patients childhood and 30-50% of adults can be put into remission, but then most of these patients experience a relapse. Even if bone marrow transplantation is performed after the first remission is achieved, five-year survival can be achieved in relatively few patients, usually young. The remaining patients are transferred to palliative care at some point. Specific data vary between publications, but survival figures for AML are still significantly lower than the average results for acute myeloid leukemia.
However, patients with AML developing due to Down syndrome usually have a favorable prognosis. Most of them (up to 80%) can be cured.
1. Acute myeloid leukemia (AML)
M0 - acute myeloblastic leukemia with minimal signs of differentiation
M1 - acute myeloid leukemia without signs of aging M2 - acute myeloblastic leukemia with signs of aging M3 - hypergranular acute promyelocytic leukemia M3v - microgranular acute promyelocytic leukemia M4 - acute myelomonoblastic leukemia M5a - acute monoblastic leukemia without signs of aging M5b - acute monoblast ny leukemia with signs of maturation M6 - acute erythroblastic leukemia (erythroblastic leukemia) M7 - acute megakaryoblastic leukemia
2. Acute lymphoblastic leukemia (ALL) L1 - microlymphoblastic ALL
L2 - ALL with typical blasts L3 - macrolymphoblastic ALL
Table 14-13. Cytochemical features of blast cells in acute leukemias of various origins
Note. MPO - myeloperoxidase; -NAE—naphthyl acetate esterase; CAE - chloroacetate esterase; KSM – acidic sulfated mucopolysaccharides; "-" - negative reaction; “+” - positive reaction in single cells; “+” - weak reaction; “++” - moderate reaction; “+++” is an intense reaction.
The identified nosological forms of acute leukemia differ in clinical characteristics and, most importantly, in response to cytostatic drug therapy. In adult patients, myeloblastic and lymphoblastic variants are more common, in children - lymphoblastic and (less often) undifferentiated variants of acute leukemia.
Acute undifferentiated leukemia, variant M0. The morphological substrate of the tumor is represented by cells of classes II-III according to the modern scheme of hematopoiesis, which morphologically resemble lymphoblasts, but differ in cytochemical intactness (see Tables 14-13). Typical chromosomal abnormalities for MO are monosomy 7, trisomy 4, 8, 13.
Acute myeloblastic leukemia. It is a tumor arising from the precursor cell of myelopoiesis and consisting predominantly of the parent cells of the granulocytic series - myeloblasts. There are 2 variants of AML - M1 And M2, which are characterized by chromosome translocations t(9;22) and t(8;21), respectively. In the bone marrow and blood of patients with AML, numerous medium-sized myeloblasts with a narrow rim of non-granular cytoplasm and large myeloblasts with extensive (sometimes vacuolated) cytoplasm with azurophilic granules and 1-2 Auer rods are found (they can be detected in more mature cells of the granulocytic series). Mature neutrophils are characterized by hyper or hyposegmentation of nuclei and “depletion” of cytoplasmic granularity.
Acute promyelocytic leukemia. Leukemic cells in this form of acute leukemia are characterized by chromosome translocations: t(15;17), t(5;17), t(11;17). Atypical promyelocytes contain a large number of large ones (in the hypergranular variant - M3) or small (with microgranular variant - M3v) granules and Auer sticks (often 1O-2O or more). When Auer rods fuse, they form "fagot cells"- cages with a “bundle of rods”. The nuclei of atypical promyelocytes have a loose chromatin structure, irregular shape with blurred contours (sometimes their shape is indistinguishable due to the abundance of granules in the cytoplasm).
Acute monoblastic leukemia. There are two versions of it - without signs of cell ripening (M5a) and with signs of cell ripening (M5b), in which translocation rearrangements of chromosomes t(9;11) and t(4;11) are detected. In M5a, the tumor substrate consists of large-sized monoblasts with extensive
gray-blue cytoplasm, scanty azurophilic granularity and vacuolization. With M5b, the predominant cell type in the bone marrow and blood are promonocytes (the number of monoblasts does not exceed 10-15%).
Acute myelomonoblastic leukemia or M4 variant of acute leukemia. It is based on rearrangements of chromosome 16: inv (16), t(16;16), t (8;16). M4 is characterized by the presence in the bone marrow of two types of atypical blasts simultaneously - myeloblasts and monoblasts. Promonocytes can also be found in the blood.
Acute erythroblastic leukemia or M6. The most common cytogenetic anomaly in M6 is deletion of the long arm of chromosome 5 or 7. The tumor substrate consists of cells of the erythroid series: erythronormoblasts, giant, multinucleated erythrokaryocytes with a megaloblastic tint, megaloblasts, abnormal erythroid cells with vacuolated and processed cytoplasm, with karyorrhexis. In the blood, pronounced aniso- and poikilocytosis, hyperchromia of erythrocytes, the appearance in the bloodstream of erythrocytes with basophilic granularity, Cabo rings, erythroblasts, polychromatophilic and oxyphilic erythronormoblasts are observed.
Acute megakaryoblastic leukemia, variant M7. The characteristic cytogenetic features of M7 are inv (3), t(3;3), t(1;22). Megakaryoblasts and their fragments are detected in the bone marrow and blood. Thrombocytosis is detected in the blood (more than 1000-10 9 /l). Platelets are gigantic in size, can stick together in “heaps”, there is a qualitative cell defect - “gray” platelets (as a result of a defect in α-granules).
Acute lymphoblastic leukemia. It is a tumor arising from a lymphopoiesis progenitor cell. In the bone marrow of ALL, total lymphoblastic metaplasia is detected. The picture of peripheral blood in ALL is characterized by the presence of blast cells. According to the FAB classification, depending on the cytomorphological characteristics of lymphoid cells, three cytological variants of ALL are distinguished: L1 (microlymphoblastic), represented by a homogeneous population of small-sized cells; L2 (with typical blasts), characterized by heterogeneity of cells, among which large cells predominate; cells of medium and small sizes are less often detected; L3 (macrolymphoblastic), in which only large cells are found.
In 1995, the European Group for the immunological characterization of leukemias (EGIL) proposed a classification of acute lymphoblastic leukemias based on immunological principles. In accordance with the EGIL classification, they are divided into T- and B-lineage leukemias (Table 14-14).
Table 14-14. EGIL classification of acute lymphoblastic leukemia (ALL)
Chronic leukemia. The classification of chronic leukemia can be somewhat simplified as follows. 1. Chronic myeloproliferative leukemias: Chronic myeloid leukemia
Ph-positive (typical, adult type)
Ph-negative (atypical, juvenile type) Chronic myelomonocytic leukemia Chronic neutrophilic leukemia Chronic eosinophilic leukemia Chronic basophilic leukemia
Chronic mast cell leukemia Polycythemia vera (erythremia) Thrombocythemia
Chronic idiopathic myelofibrosis (subleukemic myelosis)
2. Chronic lymphoproliferative leukemias:
B-cell chronic lymphocytic leukemia Chronic lymphocytic leukemia Hairy cell leukemia Paraproteinemic hemoblastoses
Multiple myeloma (myeloma disease)
Waldenström's macroglobulinemia
Heavy chain diseases
T- and NK-cell (from NK-cells - natural killer) chronic lymphocytic leukemia
Sézary's disease (lymphomatosis of the skin)
Leukemia of large granule-containing lymphocytes (NK cells)
Unlike acute leukemia, the monoclonal (“benign”) stage of chronic leukemia is longer (years, decades). In the development of chronic leukemia, a chronic phase is distinguished, which is characterized by a long compensated course, and a phase of blast transformation, manifested by a blast crisis with a sharp increase in the number of blast cells in the bone marrow and peripheral blood (more than 30%), progression of anemia, thrombocytopenia and the formation of extramedullary leukemia. infiltrates.
The clinical and laboratory picture of chronic leukemia is characterized by a variety of signs that are strictly specific to a particular form of the disease. The most common types of chronic leukemia are chronic myeloid leukemia, chronic myelomonocytic leukemia, erythremia, subleukemic myelosis, chronic lymphocytic leukemia, paraproteinemic hemoblastoses and cutaneous lymphomatosis.
Chronic myeloid leukemia. One of the most common diseases in the group of leukemias. The morphological substrate of chronic myeloid leukemia (CML) is mature and maturing cells of the granulocytic lineage of hematopoiesis (the leukoerythroblastic ratio in the bone marrow increases to 20:1, while 2:1-4:1 is normal). According to modern concepts, CML occurs as a result of a somatic mutation in the stem cell-precursor of myelopoiesis, which in 85-95% of cases leads to the formation of a chromosomal marker - Ph "chromosome (see Fig. 14-12), which is the product of a deletion of chromosome 22 or translocation the distal part of the long arm of chromosome 22 onto chromosome 9. In children, CML occurs in two variants - with the Philadelphia chromosome in the karyotype of leukemic cells (adult type of the disease) and without it (juvenile type).
The course of chronic myeloid leukemia in both adults and children is divided into stages or phases of the disease depending on the degree of maturity cellular composition blood. IN chronic phase In typical CML, the total number of leukocytes in the peripheral blood ranges from 50-10 9 /l or more (in 25% of patients - more than 350-10 9 /l). Neutrophilic leukocytosis with a pronounced nuclear shift to the left is noted: single myeloblasts (2-3%), promyelocytes, myelocytes, metamyelocytes, rod- and segment-nuclear forms of granulocytes are found. The number of promyelocytes and myelocytes increases as the disease progresses, while the number of band and segmented forms of granulocytes decreases. Severe eosinophilia and basophilia (eosinophilic-basophilic association) are noted. Signs of degeneration are found in granulocytes - pseudopelgerization, low alkaline phosphatase activity. In children, the juvenile (Ph-negative) form of CML is characterized by high monocytosis and thrombocytopenia. IN period of blast transformation There is a sharp “rejuvenation” of the leukocyte formula due to an increase in the number of promyelocytes and myeloblasts (at least 30%), cytopenia progresses (anemia, leukocytopenia and thrombocytopenia), leukemic infiltrates occur in the skin, lymph nodes, myocardium and other organs. Karyological examination reveals the polyclonal nature of pathological cells (aneuploidy), which is the main sign of the terminal stage - a new stage of tumor progression.
Chronic myelomonocytic leukemia characterized by hypercellularity of the bone marrow due to an increase in the number of immature and mature cells of the granulocyte and monocytic series (promonocytes, monocytes). Myeloblasts and monoblasts make up no more than 5% of the total number of myelokaryocytes. In the peripheral blood, immature cells of the neutrophil series (no more than 10% of the total number of leukocytes), promonocytes, and, less commonly, blasts are found. In granulocytes - pseudopelgerization, “depletion” of granularity in the cytoplasm, a negative reaction to myeloperoxidase, low activity of leukocyte alkaline phosphatase. A high content of lysozyme is established in the blood serum and urine.
Erythremia (polycythemia vera, Vaquez disease). A disease of a tumor nature, characterized by a relatively benign course. The source of tumor growth is the precursor cell of myelopoiesis, the main substrate of the tumor is erythrocytes. The most characteristic changes are in the peripheral blood: the number of erythrocytes reaches (6-12)-10 12 / l, the hemoglobin level - 180-220 g / l, the hematocrit increases to 60-80%. The level of erythropoietin in the blood and urine, in contrast to symptomatic erythrocytosis, remains normal. There is leuko- and thrombocytosis, ESR decreases, blood viscosity increases. An important diagnostic sign is an increase in the mass of circulating red blood cells, which mediates hyperemia of the skin and mucous membranes, microvascular occlusion and associated headaches, pain in the joints, spine, epigastrium, etc.
Subleukemic myelosis characterized by hypercellularity of the bone marrow due to hyperplasia of the granulocytic, erythroid and megakaryocyte lineages, as well as myelofibrosis and myelosclerosis, with the progression of which the cellularity of the bone marrow gradually decreases. Immature granulocytic cells, hypo- and hypersegmented neutrophils, and myeloblasts (1-5%) are found in the blood. The platelet count varies. Large hypogranular platelets are often detected: abnormal megakaryocytes and their fragments. Hematological signs of subleukemic myelosis, which make it possible to differentiate it from CML, along with pronounced fibrosis and sclerosis of the bone marrow, are: an increase in the total number of leukocytes in the blood no more than 50-10 9 / l (with CML more than 50-10 9 / l), moderate basophilia with a normal content of eosinophils (with CML, a combined increase in the number of basophils and eosinophils - eosinophil-basophil association) and high alkaline phosphatase activity in neutrophils (in CML, leukocyte alkaline phosphatase activity is low).
Chronic lymphocytic leukemia. This is a tumor of immunocompetent tissue, consisting predominantly of mature lymphocytes, represented in most cases by B cells. Leukocytosis is characteristic; In blood smears, mature narrow cytoplasmic lymphocytes predominate, the content of which can reach up to 80% or more. An important sign is the appearance of degenerative forms of lymphocytes - Gumprecht's shadows (the result of crushing qualitatively inferior lymphocytes during the preparation of hematological smears), naked nuclei of lymphocytes and Reader's forms. The number of lymphocytes in the bone marrow is at least 30% of all myelokaryocytes. The proliferation of lymphoid tissue occurs in the lymph nodes, spleen and liver, which is accompanied by an increase in these organs.
The functional inferiority of tumor-forming lymphocytes leads to disruption of immunological homeostasis in patients, which, in turn, becomes the cause of autoimmune conflicts (autoimmune hemolytic anemia and thrombocytopenia); infectious complications (due to impaired antibody formation), etc.
Unlike chronic myeloid leukemia, blast crises are observed extremely rarely, and secondary resistance to cytostatic drugs does not develop.
Paraproteinemic hemoblastoses. Paraproteinemic hemoblastoses include myeloma (multiple myeloma, plasmacytoma), Waldenström's macroglobulinemia and heavy chain diseases - tumors of B-cell origin. The main feature of these leukemias is the preservation of the ability of B cells to differentiate to the stage of immunoglobulin-secreting cells. At the same time, the immunoglobulins they secrete are characterized by uniform structure (monoclonal paraproteins), which is explained by their origin from the same clone of tumor cells. Paraproteins correspond different options normal immunoglobulins (usually IgG or IgM), differing from them by the strict uniformity of heavy and light chains, or are structurally abnormal immunoglobulin molecules (isolated fragments of heavy chains, free light chains).
At multiple myeloma there is a disseminated malignant proliferation of the B-lymphocyte clone at the level of plasma cells. Multiple myeloma accounts for about 1% of all malignant neoplasms, and the incidence of multiple myeloma varies among different ethnic groups
from 1 to 10 per 100,000 population. Plasma cells most often proliferate diffusely throughout the bone marrow, but sometimes form a solitary tumor called a plasmacytoma. Due to osteolytic damage caused by the production of osteoclast-activating factors (IL-1, TNF-α, TNF-β) by tumor cells, hypercalcemia and associated damage to the nervous, cardiovascular system, kidneys, and gastrointestinal tract develop, thrombocytopenia develops, anemia, leukopenia. At the same time, the formation of normal plasma cells is suppressed, which leads to disruption of the formation of other immunoglobulins, and a syndrome of recurrent infections develops.
If paraproteins are detected during serum electrophoresis, an electrophoretic study of urine is mandatory. In 20% of myeloma cases, the tumor produces only immunoglobulin light chains, which, due to their low molecular weight, are quickly filtered in the kidneys and may not be detected in the serum, but are detected in the urine (Bence Jones proteinuria). In this regard, to confirm the diagnosis, Bence-Jones protein in the urine is determined by electrophoresis, which is located near the start of the M-gradient in the serum, between γ- and β-globulins.
Waldenström's macroglobulinemia characterized by the fact that tumor B-lymphocytes produce macromolecular monoclonal paraproteins of the IgM class. Due to the accumulation of high molecular weight proteins, increased blood viscosity, impaired microcirculation, sludge syndrome, predisposition to thrombosis, and hemorrhagic syndrome are characteristic. Mostly men over 60 years of age are affected. The blood picture is characterized by anemia, in the pathogenesis of which tumor suppression of erythropoiesis and blood loss play a role; leukopenia with neutropenia, monocytosis, and thrombocytopenia often develop as the disease progresses. The ESR is always sharply increased, there is hyperproteinemia in the serum, and the electropherogram shows an M-gradient due to IgM. Bence Jones protein is found in urine in approximately 80% of cases, but its amount is significantly less than in multiple myeloma. Unlike multiple myeloma, Waldenström's macroglobulinemia usually exhibits enlarged lymph nodes and hepatosplenomegaly, but lymphoid infiltration usually progresses relatively slowly.
At the same time bone lesions and hypercalcemia are rare. Manifestations of the disease disappear with replacement blood transfusion.
Heavy chain diseases are B-cell lymphatic tumors with a diverse clinical and morphological picture and secretion of fragments of heavy chains of various classes of immunoglobulins. These are usually α chains, but may also be γ or μ chains. There are two forms of the disease: abdominal and pulmonary. The abdominal form is characterized by diffuse infiltration of the mucosa small intestine and mesenteric lymph nodes lymphoid and plasma cells, macrophages, mast cells. Defeat gastrointestinal tract leads to atrophy of the villous epithelium and the development of malabsorption syndrome. The pulmonary form occurs with bronchopulmonary lesions and mediastinal lymphadenopathy. There is no proteinuria. Diagnosis is based on immunochemical analysis of serum proteins, which allows the detection of heavy chains of immunoglobulins.
Sézary's disease (lymphomatosis of the skin) manifested by generalized erythroderma, alopecia, damage to the eyelids, nail dystrophy, intense itching of the skin. 30% of patients have splenomegaly, 60% have lymphadenopathy of a mixed nature (some lymph nodes enlarge reactively due to the addition of skin infections, others due to their leukemic infiltration). When examining bone marrow trephine biopsy specimens, foci of lymphoid infiltration are detected from small lymphocytes and Sézary cells - atypical T-lymphocytes with light cytoplasm and folded (convolute) nuclei. The hemoglobin content, the number of red blood cells and platelets in the blood usually remain within normal limits. Characterized by lymphocytosis (up to 70-10 9 /l), the presence of Sezary cells in blood smears.
What is Acute megakaryoblastic leukemia
Acute megakaryoblastic leukemia is characterized by the presence in the bone marrow and blood of megakaryoblasts - cells with a hyperchromatic (strongly stained) nucleus, narrow cytoplasm with filamentous outgrowths, as well as undifferentiated blasts. Often, ugly megakaryocytes and fragments of their nuclei are found in the blood and bone marrow. Acute megakaryoblastic leukemia is the most common type of acute leukemia in children with trisomy 21 (Down syndrome).
Megakaryoblastic leukemia is often combined with bone marrow fibrosis (acute myelosclerosis). It responds poorly to therapy, so the prognosis is usually unfavorable.
Pathogenesis (what happens?) during Acute megakaryoblastic leukemia
When studying megakaryoblasts by electron microscopy using cytochemical staining for myeloperoxidase, a specific location of the enzyme was discovered in them ( Breton - Gorius). The above technique is used to identify megakaryoblasts. The megakaryoblastic nature of cells is determined not only using electron microscopy in combination with a cytochemical study for peroxidase, but also using antiplatelet antisera that detect specific markers on cells of this series.
With this form, ugly megakaryocytes, fragments of their nuclei and accumulations of platelets are often found in the blood and bone marrow. The level of platelets in the blood is usually higher than normal.
Symptoms of Acute megakaryoblastic leukemia
The clinical picture of acute megakaryoblastic leukemia is mostly devoid of specific features. In the outcome of the disease, suppression of normal myelopoiesis and other signs of the terminal stage are observed. In some cases, acute megakaryoblastic leukemia may have a clinical and hematological picture of acute low-grade leukemia, and according to bone marrow histology, a picture of myelofibrosis. This form of megakaryoblastic leukemia is characterized by a low percentage of blast cells in the bone marrow and blood, a polymorphic cellular composition of the bone marrow, often pronounced megakaryocytosis in the bone marrow and diffuse myelofibrosis, sometimes osteomyelosclerosis. Myelofibrosis, as a rule, does not allow bone marrow aspirate to be obtained throughout the disease. Cytological and cytochemical analysis of blast cells released into the blood, for the most part, does not reveal specific signs belonging to any germ of hematopoiesis.
This form of acute leukemia is difficult to distinguish from subleukemic myelosis with cytopenia and early appearance of blast cells in the bone marrow and blood.
Myelofibrosis and the low content of rarely dividing blasts complicate cytostatic therapy, which is necessary due to deep cytopenia. In most cases, cytotoxic therapy does not provide good effect and even worsens cytopenia. Most effective method The treatment for acute megakaryoblastic leukemia with severe myelofibrosis is bone marrow transplantation.
Which doctors should you contact if you have Acute Megakaryoblastic Leukemia?
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Myeloid leukemia is a cancer hematopoietic system body. The disease begins in the bone marrow, which produces different types of blood cells. When a person is healthy, the development and renewal of all blood cells occurs in a balanced manner. The process of cell maturation itself is quite complex and occurs gradually.
But when pathology occurs, the entire maturation process breaks down completely. White blood cells (leukocytes) cease to fully mature into full-fledged mature cells and begin to rapidly divide chaotically. The functioning of the hematopoietic system is disrupted: altered myeloid cells displace healthy ones and replace them in the bone marrow. The blood of a person with leukemia contains few healthy white blood cells, red blood cells (red blood cells) and platelets (blood platelets).
Description
Myeloid leukemia (leukemic myelosis) is one of the types of leukemia with a high level of malignancy, when pathological processes begin to occur in myeloid blood cells. The altered lymphocytes prevent healthy blood cells from growing and developing, and after some time the bone marrow completely stops producing healthy cells. Therefore, patients with leukemia often develop anemia (anemia), frequent bleeding and various infectious diseases.
From the very early stages Myeloid leukemia is not located in one specific part of the body. From the bone marrow it is carried by the bloodstream throughout the body: to the lymph nodes and other organs. The functions of the entire organ system are disrupted, which means the functioning of the entire organism as a whole. Therefore, myeloid leukemia is called a systemic malignancy.
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The disease spreads extremely quickly. In cases where there is no treatment, leukemia cells spread throughout the body unhindered. The organs into which they have penetrated cease to function normally and serious illnesses. Without treatment, patients die within a few weeks or months.
Myelogenous leukemia is considered the most common in adults. The risk of developing this disease increases sharply after age 50. middle age patients - 60 years. In young and middle age, men and women get sick equally often. In older age, men are more likely to get sick. Code for myeloid leukemia (granulocytic and myelogenous) according to ICD-10–C92.
Also in medical practice There is another type of leukemia - lymphoblastic. The difference between lymphoblastic leukemia and myeloblastic leukemia is that it develops from a group of lymphocyte precursors (lymphoblasts).
Reasons
Until now, scientists have not been able to establish the exact preconditions that give rise to a new formation of myeloid lineage and a malignant change in blood cells.
Only a number of factors are indicated that can provoke the onset of the development of myeloid leukemia:
Need to know! Transient myeloproliferative syndrome is observed in 10% of newborns with Down syndrome. In most cases, the disease is asymptomatic, except for circulating blasts in the peripheral blood, and resolves without treatment within 3-6 months.
Varieties
Myeloid leukemia is divided into two forms: acute and chronic. Forms of myeloid leukemia cannot transition from acute to chronic. These are different diseases with special typical signs. Acute myeloid leukemia is characterized by excessive proliferation and growth of immature blast cells. a very serious and difficult to treat disease. In acute myeloblastic leukemia, the disease develops rapidly, which requires timely treatment.
This disease has three stages of development:
- initial – most often goes unnoticed. During laboratory tests, changes in blood biochemistry are observed. The patient develops bacterial infections, chronic diseases worsen;
- expanded - signs of the disease appear. Sometimes exacerbations and stages of remission alternate. It happens very often. If recovery does not occur, the disease worsens and enters the terminal stage;
- terminal - characterized by a large-scale disruption of the process of healthy hematopoiesis.
Acute myeloid (or myeloblastic) leukemia can develop in people of any age, but it most often occurs in patients over 50 years of age. This is one of the most common types of blood cancer in children and adolescents. In pediatric oncology, myeloid leukemia ranks second, second only to acute lymphocytic leukemia. In children, this disease occurs in almost 25% of cases.
Myelomonocytic (myelomonoblastic) leukemia is a form of myeloid leukemia that affects red bone marrow cells in the blood: monoblasts and myeloblasts. Blasts lack Auer bodies - red protein cells in the cytoplasm of myelocytes and myeloblasts. Myelomonocytic leukemia has three clinical type: acute, chronic and juvenile.
Important! Myelomonocytic leukemia is most often observed in pediatric patients. In children under 4 years of age, the frequency of detection of this disease comes first.
Chronic myeloid leukemia is characterized by excessive abnormal formation and growth of mature and maturing leukocytes. The disease develops slowly and has no noticeable symptoms in the early stages. Very often discovered by chance laboratory analysis blood for other diseases.
Chronic leukemia also has three stages of development:
- benign – is asymptomatic for a long time, expressed by a steady increase in the number of leukocytes in the blood;
- advanced – clinical signs of the disease appear, the level of leukocytes increases;
- terminal – the patient’s health deteriorates sharply. Noted low sensitivity to the prescribed treatment, infectious complications develop.
The chronic form of myeloid leukemia most often occurs in adults, but it also occurs in children (about 2% of cases). The group of chronic myeloid leukemias includes: chronic form monocytic blood cancer, subleukemic myelosis, erythromyelosis and others.
The subleukemic type of chronic myeloid leukemia most often occurs in elderly patients. The disease accompanies the proliferation of connective tissues of the bone marrow and their replacement with scar connective tissues. Distinctive feature This type of leukemia is the absence of symptoms and complaints from the patient for a long time. There are also chronic myelocytic leukemias, a group of diseases in which tumor cells of the type of cytic or procytic precursors of the myeloid series are formed.
The WHO systematization of AML divides several dozen types of the disease into several groups:
- AML with typical gene changes;
- AML with disorders associated with dysplasia;
- secondary AML that begins as a result of therapy for other diseases;
- diseases with proliferation of myeloid lineage in Down syndrome;
- myeloid sarcomas (myelosarcoma);
- blast plasmacytoid dendritic cell tumors;
- other types of AML.
According to the FAB classification, there are also several variants of acute myeloid leukemia:
- M0 – undifferentiated AML;
- M1 – AML without cell maturation;
- M2 – AML with incomplete cell maturation;
- M3 – promyelocytic leukemia;
- M4 – myelomonocytic leukemia;
- M5 (M5a and M5b) – monoblastic leukemia;
- M6 – erythroleukemia;
- M7 – megakaryoblastic leukemia.
Symptoms
The symptoms of myeloid leukemia are characterized by the following primary symptoms:
Patients experience thinning of cartilage and increased bone fragility. The spleen produces more and more platelets to compensate for their deficiency, as a result of which it increases greatly. There is also a typical picture of the disease with characteristic symptoms: increased body temperature, night sweats, rapid heartbeat, feeling severe pain in the joints, enlarged lymph nodes, rashes on the skin and mucous membranes.
Signs of the disease such as headaches, blurred vision, vomiting, facial muscles do not move, and in boys the testicle (sometimes both) may become enlarged are less often noticed. Hypertrophy of gum tissue is noted and chloromas appear - green or bluish tumor-like formations that appear in the lymph nodes, on the bones or around the eyes.
Patients with chronic myeloid leukemia develop leukostasis, which can also manifest as priapism. If untreated, increased bleeding, which is initially expressed by petechiae, leads to such serious complications, How internal bleeding or hemorrhagic stroke.
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Diagnostics
Diagnosis of myeloid leukemia is carried out by studying various parameters of the patient’s blood and instrumental studies, such as:
- general blood test and biochemistry;
- cytogenetic study - abnormal cells are studied in which pathology is detected (Philadelphia chromosome);
- sternal puncture;
- lumbar puncture;
- puncture of lymph nodes;
- MRI and CT;
- radiography;
- scintigraphy of skeletal bones.
Must remember! Acute myeloblastic leukemia is characterized by rapid development, so early determination of an accurate diagnosis and the appointment of competent treatment is of great importance.
Treatment
Treatment of myeloid leukemia is a long-term complex therapy in a specialized medical clinic and strict monitoring of the course of the disease. The main treatment for this disease is chemotherapy. During chemotherapy, special cytostatic drugs are used that block growth cancer cells. One such drug is not able to destroy all affected cells, so doctors use combinations of several drugs that have different effects on tumor cells. Thus, maximum treatment effectiveness is achieved. The use of a combination of several cytostatics is called polychemotherapy.
Chemotherapy for myeloid leukemia is carried out in two stages: induction and consolidation (post-remission therapy). At the first stage, treatment is prescribed aimed at reducing the number of leukemia cells in the body and a state of remission is achieved. At the second stage, they are eliminated residual effects disease, and the possibility of relapse is prevented. Therapeutic measures are prescribed depending on the type of myeloid leukemia, general physical condition patient and many other factors. If necessary, radiation therapy is recommended and symptomatic treatment is carried out.
Those patients whose disease does not respond to treatment, or if the disease relapses, are prescribed courses of high-dose chemotherapy. After this they produce. The main goal of this procedure is to completely destroy leukemia cells throughout the body so that normal bone marrow functions are restored. To prevent complications after treatment, so-called accompanying therapy is used, that is, auxiliary maintenance treatment.
Forecast
The life prognosis of patients with myeloblastic leukemia depends on the stage of the disease at the time of diagnosis. The patient’s body’s response to the treatment is very important. Modern methods biotherapies make it possible to achieve stable long-term remission and prevent relapses of the disease. An unfavorable prognosis may occur in cases where the disease is discovered late.
The life expectancy of patients with myeloid leukemia can be influenced by many reasons.
The risk of mortality from this disease increases if:
- patient age over 55 years;
- there is a history of another cancer;
- available genetic mutations in cells;
- a very large number of white cells at the time of diagnosis;
- carrying out two or more courses of chemotherapy.
Important! Currently thanks to modern techniques After treatment, the prognosis for myeloid leukemia has become more favorable: the five-year survival rate of patients exceeded 75%, and long-term remission is observed in more than 50% of patients.
According to statistics, adult patients with myeloid leukemia have the following prognoses:
- Elderly people over 60 years of age have a slightly more than 10% chance of surviving to the 5-year mark;
- survival rate of people 50 - 60 years old - 25%;
- survival rate of patients 40 - 45 years - 50%;
- Young patients have a greater chance of recovery.
