Leukemia Flashcards
Definition of leukemia
It is a malignant disease (or form of hemoblastoses)of the hematopoietic system with primary damage to the bone marrow by genetically transformed tumor hemapoietic cells.
What are hemoblastoses?
-neoplastic disorders of hematopoietic tissue
They are divided into 2;
1.leukemia-tumors of blood and hematopoietic organs with primary damage to bone marrow
2. Hematosarcoma
Leukemia and hematosarcoma can change into one another , leukemia cells can metastasis into lymph nodes, spleen, tonsils and vice versa cells of hematosarcoma can get into bone marrow.
What is the etiology of leukemia?
By physical,chemical ,biological carcinogens
- ionising radiation
- chemical mutagens e.g benzene
- viruses(Epstein Barr virus-Burkitt’s lymphoma)
Heredity
- leukemia primarily develops in individuals with chromosome pathology e.g patients with Down syndrome
- chronic bone marrow dysfunction such as myeloproliferative disease, myelodysplastic syndrome, aplastic anemia, paroxysmal nocturnal hemoglobinuria.
Pathogenesis of leukemia
- leukemias have systemic character of damage caused by early metastasis and dissemination of tumor cells throughout an organism unlike cancers and sarcomas which metastase at an early stage since here tumors develop in stem cells which normally enter blood and form colonies
- leukemias have clonal origin, i.e leukemia cells represent a colony of one mutant cells and carry signs of initially mutated cells
- at first cells of colony have the same properties and are identical. This stage is called monoclonal stage.
- Polyclonal stage-with time genetic material in tumor cells loses stability causing additional mutation in them.
3.Of all subclones of leukemic cells which constitute this tumor the advantage is gained by those which are independent
Gradually leukemias undergo so called Neoplastic Tumor Progression which consists in irreversible qualitative changes in tumors which increase malignancy of cells.
Most important signs of progressing hemoblasts
- 2 stages of development-monoclonal and polyclonal stage
- Inhibition of normal hemopoiesis
- Replacement of differentiated cells with blast cells (e.g blast crica in terminal stage of chronic myeloleukemia)
- changes in morphology and in enzymatic specificity of the blast cells which makes them non-identifiable
- appearance of metastases in skin, arachnoid membrane kidneys etc or dissemination (spread of lymphoma into brain)
- escape of tumor out of control of cytostatic therapy when it becomes resistant to earlier efficient treatment
Classification of leukemia
By cytomophorlogical properties of tumor substrate leukemia is divided into acute and chronic
1.Acute leukemia-blasts acquire an ability to unlimited autonomous (self governed) division but loose ability to differentiate
The result immature cells entering blood and blasts becoming morphological carrrier for tumors
Onset is rapid, very aggressive
2.Chronic leukemia-neoplastic cells acquire ability to differentiate due to which tumor is represented in blood by mature and maturing cells
However differentiation is incomplete and cells appear to various morphological cell and full defect
Onset is not rapid and less aggressive
Classification of Acute leukemia
Depending on what line of hemopoiesis is affected -myeloblast
- lymphoblast
Also - monoblast,erythromyelosis,megakaryoblast,plasmoblast,promylocytic, blast cell (stem cell ) nondifferentiable leukemia.
According to French-American-British classification
Nonlymphoblast myelogenic leukemia
Lymohoblast leukemia
Myelopoetic dysplasia or myelodysplastic syndrome
Clinical picture of acute leukemia
Clinical picture-patient will be anemic,presence of hemorrhagic syndrome in the form of ptechaias, hematomas, gingival bleeding
Immunodeficiency is expressed as tonsillitis,gingivitis,infection
Infiltration of organs shown by pain in bones and joints
Infiltration of brain seen by headaches
On physical examination-
Palpation of liver and spleen shows hepatosplenomegaly
Lymph nodes Palpation shows enlarged peripheral lymph nodes
Intoxication
Weight loss
High temperature
Specific symptoms of leukemia
1.painful ness of bone(tubular +spine) in result of hypeplasis of bone marrow
2.lymphadenopathy due to proliferation of lymphoid cells
3.Hepatosplenomegaly in result of development of foci of extra medullary hemopoiesis and infiltration of medulla with leukemic cells
4.Neuroleukemias(in acute lymphoblast leukemia) due to metastasise in arachnoid membrane, spinal cord and into brain matter
5,Leukemids of skin(nodules) mostly myeloblast or monoblast
6. Hypertrophy of thymus
Lab instrumental diagnosis of Acute leukemia
CBC- neutrophilic leukocytosis with left shift, normochromic sometimes hypochromic due to thrombocytopenia and hemmorrhage Biochemical CT US X-ray ECG Routine urine analysis Immunophenotyping Bone marrow examination
Leukemoid reaction-specific change in CBC not related to leukemia
For example extremely high leukocyte count, in infection sepsis, glucocorticosteroids, increase in WBCs
Methods of specific diagnosis of acute leukemia
- bone marrow cytology
Trepanobiopsy-bone marrow histology
Cytochemical study
Flow cytometry(immunophenotyping)
Cytogenetics-method of differentiated chromosome staining (banding)
FISH- fluorescence insites hybridisation
Molecular biopsy- PCR determination of chimeric gene expression
Treatment of Acute leukemia
1.Specific cytostatic therapy (chemotherapy, X-ray radiation)which suppresses proliferation of cells in bone marrow
Symptomatic treatment
Transfusion of erythrocytes in anemia, transfusion of platelets in hemorrhagic syndrome
To prevent infection antibiotics, anti fungal
To prevent uric acid stone-alapurinol, stem cell transplant
Transplantation of bone marrow
Accompanying therapy-measures against intoxication,elimination of anemia
Classification of chronic leukemia
Chronic myeleukosis
Chronic lympholeukosis
1.Chronic myeleukosis
-occurs more in adults 20% , in children 5%
-leukocyte count maybe 20-40 x10^4/l or in some cases 80-100x10^9/l
-in blood all representatives of myeloid cells are detected but mature and maturing cells predominate
Basophils decreased, eosinophils are increased
Clinical picture- pain in the bones,joints,rapid fatigability even on slight exertion, hyperhidrosis,low grade temperature,weight loss,bleeding disorders,paleness,skin hemorrhages
On examination we see hepatomegaly,splenomegaly, 50% of patients develop splenic infarction which manifests by pain in the left hypochondrion that radiates to the left side,left upper arm,and increases on deep inspiration
Lab instrumental diagnosis-anemia, increase ESR,WBC count up to 200-400x10^9/l with left shift of promyelocytes, usually all intermediate forms up to mature granulocytes are present
Exact diagnosis of leukemia requires puncture trepanobiopsy with evalaluation of myelogram.
Chronic lympholeukosis- is a variant of leukemia where morphologic substrates are mature and maturing lymphocytes which are functionally insufficient and do not perform their main immunologic protective functions
It has a benign course and absence of tumor progression in almost all cases
Clinical picture-at the beginning of the disease the patients condition is satisfactory, however enlarged peripheral lymph nodes are seen.
In the period of full manifestation generalised enlargement of lymph nodes, spleen and of retro peritoneal, me sent Eric, mediastinal lymph nodes
Peripheral lymph nodes aref painless, soft to Palpation, hepatomegaly, patients have severe intoxication , weakness,hyperhidrosis,weight loss, anorexia, rise in temperature, pain in bones, skin itch
Lab instrumental diagnosis-leukocytosis up to 200x10^9/l, sharp increase in lymphoctes count, some prolymphoctes,lymphoblasts, Botkin-Gumpecht cells in large quantity, increase ESR, anemia, biopsy of lymph nodes, abdominal US for liver,spleen,lymph nodes. Chest X-ray to evaluate retrosternal and paratracheal paratracheal lymph nodes.
Also:
Erythemia- polycythermia Vera, Vaquez disease
Increase Hb(180-220g/l); increase RBCs (6,8-8x10^6/l), increase hematocrit, increase viscosity of blood, decrease ESR to the extent of full cessation of sedimentation, neutrophilic leukocytosis(9-15x10^9/l and higher), left shift, sometimes mild eosinophilia, increase platelets.
Chronic monocytic leukemia- its many years benign
Persistent monocytes is (30-40%) , moderate leukocytosis (1,5-2x10^9/l), increase in monocytes in bone marrow puncture up to 30%, increase in concentration of muromidase enzyme/lysozyme and its excretion in urine.
Paraproteinemic hemablastosis- myelomatosis, macroglobulinemia- waldenstromidesens
Tumor of b-cell, pathological Ig production (pIg),myelomatosis(plasmocytome), normo chronic anemia, increase ESR, granulocytopenia,sometimes myelogenetic cells are detected in blood dnears(pIG > 30g/l), concentration of normal Ig decreases
Causes of chronic leukemia
Myeloleukosis
Lympholeukosis
Clinical picture of chronic leukemia
It’s a symptomatic at first then later Enlarged lymph nodes Dyspnea Tachycardia Increase risk of for splenomegaly infection
Lab instrumental diagnosis of Chronic leukemia
CBC-increase WBCs , lymphocytes. They are increases but both relative and absolute, basophils,eosinophils,myelocytes
FISH
Bone marrow investigation
Treatment of Chronic leukemia
We first observe them treat
If lymphocyte count 60%;
1.in remission- observation
2.exacerbation- chemotherapy
