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Acute leukoses

Table of contents
Acute leukoses
Treatment of acute leukoses

The general sign integrating various forms of acute leukoses is the characteristic substrate of a tumor provided by young, so-called blast cells.

Epidemiology see Hemoblastoses

Etiology and pathogeny see Hemoblastoses

Classification
Differentiation of various forms of acute leukoses is based mainly on features of the morphological and cytochemical characteristic of blast cells. According to data of literature and WHO recommendations among acute leukoses distinguish the following main forms.

Acute miyeloblastny
Acute miyelomonoblastny
Acute promiyelotsitarny
Acute erythremic myelosis, Di Guglielmo's illness
Acute megakarioblastny, including option with a myelofibrosis
Acute low-percentage
Acute lymphoblastoid (unripe prevail, mature T - and B-phenotypes are more rare)
Acute nondifferentiable
Eosinophilic, basphilic, plazmoblastny acute leukoses meet seldom.

Immunophenotyping of blast cells allows to allocate suboptions of an acute lymphoblastoid leukosis: pre - In - a form, pre, the V-form, the T-form, neither T - nor the V-form, nor T - nor the V-form with Ph '-a chromosome. On the basis of the unique phenotype different from an antigenic range of end-stage lymphocytes, early recognition of the progressing leukemic population when it is not possible by means of morphological methods of researches is carried out. At acute not lymphoblastoid leukoses immunophenotyping of blast cells was less informative.

Approximate formulation of the diagnosis:
1. An acute miyeloblastny leukosis (the first attack) with increase in a spleen, liver, cervical and axillary lymph nodes, anemia, a hemorrhagic thrombocytopenic syndrome, ulcer and necrotic damage of a mucous membrane of an oral cavity and a gullet against a deep granulocytopenia, with intoxication (full kliniko-hematologic remission).
2. An acute promiyelotsitarny leukosis, resistant to treatment, with expressed blastozy blood and marrow, the multiple hemorrhages (including in a brain) which developed against deep thrombocytopenia and the disseminated intravascular coagulation.
3. An acute lymphoblastoid leukosis (the second recurrence) with blastozy blood and marrow, increase in peripheral and mediastinal lymph nodes, a spleen and a liver, anemia, a hemorrhagic syndrome, ossalgiya, intoxication, right-hand nizhnedolevy bronchial pneumonia (partial kliniko-hematologic remission).
4. An acute low-percentage leukosis with low accruing blastozy blood and marrow, anemia and thrombocytopenia, insignificant increase in a spleen and liver.

Clinic
Clinical displays of acute leukoses consist generally of hyperplastic, hemorrhagic and ulcer and necrotic syndromes.

Patients quite often see a doctor concerning fast fatigue and decrease in working capacity. In a gemogramma during this period various quantity of blast cells or an absolute lymphocytosis already comes to light. Total number of leukocytes is increased or reduced, is tended to anemia and thrombocytopenia, usually do not find increase in a liver, a spleen, peripheral lymph nodes. Sometimes at the first inspection of change in a gemogramma are insignificant or at all are absent, but there is already some increase in a spleen, peripheral lymph nodes. In similar cases verification of the diagnosis is based on data of a miyelogramma in which the percent of blast forms happens rather high, the exception is made by cases of a so-called low-percentage acute leukosis (less than 15 — 20% of blasts).

Acute Miyeloblastny Leukosis (AML). The acute beginning and fast development of clinical symptoms are inherent in it. Fever, ostealgias are often noted. At a deep granulocytopenia there are ulcer and necrotic damages of a mucous membrane of an oral cavity, a gullet, intestines, symptoms of the general intoxication. The spleen, lymph nodes, a liver are usually increased in sizes. Anemia, a hemorrhagic thrombocytopenic syndrome, a specific infiltration of kidneys, a uterus, skin join.

Leukemic myeloblasts have various size (from 10 to 25 mk), the correct rounded shape or oval outlines. Nucleocytoplasmic ratio low or average. Cytoplasm of cells of gray-blue color. It contains azurophilic granularity in some cells, Auer's stick meets. Kernels of cells have the round form more often. Structure of nuclear chromatin gentle, in kernels find 1 — 4 kernel of various size.

Presence of phospholipids, peroxidases and hloratsetatesteraza (table) is characteristic of blast cells at OML. At certain patients the initial stage of a disease is characterized by a so-called erythroblastic phase when in marrow find a large number of the erythroblasts supporting two, three quite often overwound kernels. This phase is replaced quickly enough by a marrow myeloblastosis.

The main cytochemical characteristics of blast cells at acute leukoses

Forms of acute leukoses

Poly-
saccharites

Glyukuro-
nidaza

Fosfo-
lipids

Peroxidase

Hloratse-
tatesteraza

Nonspecific esterase

Acid
the sulphated mucopolysaccharides

Miyeloblastny

+

+

+

_

Miyelomonoblastny

+

+

+

+

Moioblastny

 

 

 

 

 

+

Promiyelotsitarny

+

+

+

+

+

+

+

Erythroblast

+

Lymphoblastoid

+

+

Nedifferen-
tsiruyemy

___

 

Miyelomonoblastny and monoblast acute leukoses. For them especially
the hyperthermia, the expressed intoxication, ulcer and necrotic processes, a frequent specific infiltration of gums are characteristic.

Leukemic monoblasts have the average sizes (to 20 mk), the low or average nucleocytoplasmic relation. Cytoplasm of gray-blue color with gentle powdered granularity, sometimes with the advent of budding. Kernels of the most various form: round, concave, paliform, with rough structure of chromatin; they contain 1 — 3 accurately limited large a kernel. Such blast cells meet in various ratios typical leukemic myeloblasts (a miyelomonoblastny acute leukosis), only monoblasts (an acute moioblastny leukosis) sometimes meet. Positive reaction to nonspecific esterase (substrate and-naftilatsetat) is inherent in monocytes and their predecessors. At addition in incubating medium of fluoric sodium v reaction in these cells is suppressed. At a miyelomonoblastny acute leukosis along with it also positive cytochemical changes on phospholipids, peroxidase and a hloratsetatesteraza come to light (see the table).

At an acute promiyelotsitargyum a leukosis the leading sign is the hemorrhagic syndrome which is often arising several months prior to development of the expressed clinical picture. Believe that in a pathogeny the leading role belongs to the IDCS. Intoxication, the increased perspiration and the general weakness accrue slowly. Peripheral lymph nodes, a spleen and a liver are usually not increased. Often hemorrhages in a brain are a proximate cause of death.

Leukemic blast cells of the average size. In various degree the cytoplasm basophilia is expressed, in it plentiful granulation" partially or completely covering a kernel is found. Multiple, similar to azurophilic, very small granules colourings of the cytoplasm make impression. In some cells Auer's sticks, sometimes in a large number the forming bunches meet. At this form of a leukosis positive cytochemical changes on polysaccharides, 0 glucuronidase, phospholipids, peroxidase, chloroacetate-esterase, nonspecific esterase and the acid sulphated mucopolysaccharides are noted (see the table).
At seldom found acute erythroblast leukosis peripheral lymph nodes, a liver, a spleen are, as a rule, not increased. Eristroblastoz of marrow having lines of a cellular atipizm is combined with normo-or hyperchromic anemia, leucio-and thrombocytopenia.

Erythroblasts of the big sizes with a fringed outline of cytoplasm, contain in it vacuoles, granularity. Multinucleosis, an asynchronism in maturing of a kernel and cytoplasm is noted, detection in blasts of polysaccharides while other cytochemical changes are negative is characteristic (see the table).

At the acute megakarioblastny leukosis which is found seldom in blood and marrow along with a small amount of nondifferentiable blast cells find increase of maintenance of megakaryoblasts, megacaryocytes (in the form of ugly forms with splinters of kernels) and accumulations of thrombocytes. For identification of megakaryoblasts use a submicroscopy method in combination with cytochemical research on peroxidase, and also antithrombocytic antiserums which reveal specific markers on these cells. At histologic studying of marrow find a picture of a myelofibrosis, an osteomyelosclerosis in certain patients.

The acute low-percentage leukosis meets among persons 60 more often — 70-year age, during 1 — 3 flying does not progress, proceeds with the low maintenance of blasts in marrow and blood (usually within less than 10 — 20%), is more often with persistent anemia, lack of a reticulocytosis or with a pancytopenia; at young people with low, slowly increasing blastozy blood and marrow. Progressing of process is followed by increase of a blastoz, is frequent increase in the sizes of a spleen, liver. The chemotherapy is a little effective, remissions are short and are observed seldom.

Secondary leukoses — the leukoses induced by cytostatic drugs, radiation and chemical mutagens. They can arise at patients with other forms of hemoblastoses, epithelial tumors, not tumoral diseases and proceed in the form of acute nelimf of regional leukoses, miyeloblastny, miyelomonoblastny and erythroblast forms.

Frequency of developing of secondary leukoses increases at aged people 50 years are more senior. Features of a clinical current are lack of organ defeats, a hyperthermia, a deep cytopenia, the expressed marrow fibrosis connected with radiation therapy or with an acute leukosis, in peripheral blood single blast cells can come to light. From kariologichesky features lack of the 5th, 7th or both of these chromosomes or a short shoulder at one of them, a trisomy of the 8th chromosome are noted. Development of remission at secondary leukoses usually does not manage to be gained or they happen very short.

Unlike OML the acute lymphoblastoid leukosis (ALL) is usually characterized by less rough progressing of process though in an initial stage of an illness at certain patients can already come to light a hyperleukocytosis, the expressed hyperadenosis, a spleen and a liver, anemia, a hemorrhagic syndrome, ossalgiya, intoxication.

Leukemic lymphoblasts have the correct rounded shape; the kernel occupies the most part of a cell, it, as a rule, contains one kernel; cytoplasm narrow. These cells are characterized by a high nucleocytoplasmic ratio.

Cytochemical research shows that from 1 to 90% of blast cells contain the polysaccharides (see the table) revealed by means of PAS reaction in the form of granules of various sizes. In lymphoblasts do not find phospholipids, peroxidase, chloroacetate - and nonspecific esterase. Activity of such enzymes as and - naphthylacetateesterase and acid phosphatase, reveal only in some cells in the form of 1 — 3 granules; blast cells possess very low activity of nucleases. Superficial membranes of blast cells at 1/3 adults of sick OLL bear markers of T-cells. More often at them there are markers of unripe stages of T - and V-lymphocytes. At the T-cellular form of an acute leukosis from the very beginning of a disease the high leukocytosis, significant increase in lymph nodes, including in a mediastinum are observed. Blasts of the T-cellular origin are characterized by high activity of acid phosphatase, availability of enzyme of a terminal dezoksinukleotidiltransferaza in them. The T-cellular leukosis is characterized by the most adverse forecast.

At the acute nondifferentiable leukosis meeting in isolated cases, blast cells more often morphologically remind lymphoblasts. Immunological researches quite often possible to establish the lymphoid nature of blasts. However their cytochemical intaktnost (see the table) and, therefore, impossibility of specific identification were the basis for allocation of this form of a disease.

Clinical manifestations of the pathomorphism of acute leukoses induced by modern cytostatic therapy are the hypoplasia of a hemopoiesis, an infection, damage of a liver, digestive tract, is more rare — hearts, a nervous system.

The interrelation between the frequency of infectious complications and level of decrease in number of granulocytes in a gemogramma (a cytostatic agranulocytosis) is noted. Exposure of patients to infections is caused also by decrease in number of T - and V-lymphocytes, reduction of maintenance of a lysozyme and IgG, and also the englobing neutrophils. More than at 40% of patients pneumonia, sepsis are observed. Also abscesses, phlegmons, quinsies, ulites meet. Infectious complications of virus and fungal genesis meet less often. Liver pathology quite often from the outcome in dystrophy ayyavlyatsya more than at 20% of patients with acute leukoses and is caused by a leukemic infiltration, intoxication connected with accession of septic and necrotic processes.

Ulcer and necrotic changes of mucous membranes of a digestive tract are clinically shown by a pain syndrome and dispepsichesky frustration.

Neuroleukosis — typical display of an acute leukosis in the conditions of modern cytostatic therapy. On the observations made in VGNTs it developed at 13,5% of patients with various options of a disease.

Encephalomeningitis diagnosed for 69% of patients, defeat of cranial nerves — for 22%, local defeat of substance of a head and spinal cord — for 4,5%, defeat of roots and peripheral nerves — for 4,5%.

Verification of the diagnosis
The diagnosis of an acute leukosis is established on the basis of clinical symptomatology, results of research of a gemogramma and punctate of marrow in which, as a rule, find a significant amount of imperious cells. In differentiation of various forms of leukoses the cytochemical characteristic of blast cells is important (see the table). The immunological characteristic of cells allows to differentiate T - and the V-forms differing in certain clinical features. In cases when blast cells in a miyelogramma make only 10 — 20%, existence in a trepanobioptata of marrow of the proliferat consisting of blast cells confirms the diagnosis of an acute leukosis.

Certain difficulties meet when carrying out differential diagnosis between an acute miyeloblastny leukosis and a myelosis in an early phase of a blastemiya. Detection of PH' - chromosomes in blast cells of punctate of marrow testifies in favor of chronic, a myeloleukemia.

The acute leukoses proceeding with a pancytopenia and lack of blast cells in peripheral blood should be differentiated from hypoplastic (aplastic) anemia and an osteoblastic form of the cancer metastasizing in marrow from a stomach, a mammary gland and other bodies.
Sometimes it is necessary to carry out differential diagnosis with the infectious mononucleosis, an agranulocytosis proceeding with increase in number of blast cells in marrow punctate, leukemoid tests.


 
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