Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and
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2 Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and / or peripheral blood
3 Classified based on cell type involved and the clinical course 1. Acute : ALL( acute lymphoblastic leukemia) AML( acute myeloid leukemia) 2. Chronic : CLL CML
4 ALL Common type( pre-b) B-cell T-cell Undifferentiated
5 ALL L1: Predominantly small cells with scanty cytoplasm; membrane regular; nucleoli indistinct ALL L2: Large cells, heterogeneous in size with moderate amount of cytoplasm; nuclear membrane is irregular with clefting; nucleoli 1-2 and prominent ALL L3: Large cells with moderate amount of deeply basophilic cytoplasm; prominent cytoplasmic vacuoles; regular nuclear membrane; 1-2 prominent nucleoli
6
7 AML French-American-British (FAB) Classification M0: Minimally differentiated leukemia M1: Myeloblastic leukemia without maturation M2: Myeloblastic leukemia with maturation M3: Hypergranular promyelocytic leukemia M4Eo: Variant: Increase in abnormal marrow eosinophils M4: Myelomonocytic leukemia M5: Monocytic leukemia M6: Erythroleukemia (DiGuglielmo's disease) M7: Megakaryoblastic leukemia Ref-Harrison s Principle of Internal Medicine
8 Myelomono
9 Malignant transformation of a myeloid precursor cell ; usually occurs at a very early stage of myeloid development Rare in childhood & incidence increases with age
10 Unknown / De-novo!! In majority Predisposing factors: Ionizing radiation exposure Previous chemotherapy : alkylating agents Occupational chemical exposure : benzene Genetic factors: Down s Syndrome, Bloom s, Fanconi s Anemia Viral infection ( HTLV-1) Immunological : hypogammaglobulinemia Acquired hematological condition -Secondary
11 M > F ALL which predominantly affects younger individuals AML adults and the elderly Median age gp-65yrs Geographical variation-none
12 General : Onset is abrupt & stormy (usually present within 3 months) Bone marrow failure (anemia, infection,bleeding) Bone pain & tenderness
13 Specific: M2 : Chloroma:-presents as a mass lesion tumor of leukemic cells M3 : DIC M4/M5 : Infiltration of soft tissues, gum infiltration, skin deposits,meningeal involvement-headache, vomiting, eye symptoms
14
15 Skin Infiltration with AML (Leukemia Cutis)
16 Blood count : WBC usually elevated (50,000-1,00,000 / cmm ); may be normal or low; often anemia & thrombocytopenia Blood film : (as above) Blast cells
17 P. Smear AML
18
19 Bone marrow aspirate & trephine: Hypercellular, blast cells ( > 20%), presence of Auer rods - AML type Cytochemistry : Special stains to differentiate AML from ALL ; Positivity with Sudan black & Myeloperoxidase (MPO) in AML
20 Auer Rods in Leukemia cells
21 MPO (right) & Sudan black (left) showing intense localised positivity in blasts
22 Confirmation: Immunophenotyping Molecular genetics Cytogenetics: Chromosomal abnormalities
23 Other Inv: Coagulation screen, fibrinogen, D- dimer RFT, LFT LDH, Uric acid Urine CXR ECG, ECHO
24 I. Supportive care : Anemia red cell transfusion Thrombocytopenia platelet concentrates Infection broad spectrum IV antibiotics Hematopoietic growth factors : GM-CSF, G-CSF Barrier nursing Indwelling central venous catheter
25 CHRONIC LEUKEMIAS Patient with chronic leukemias usually survive more than one year after the onset of symptoms, if no remission occurs. The cell type is more differentiated.
26 Chronic Lymphocytic Leukemia (CLL): Rare under the age of 40, most cases occur over age of 60, has an insidious onset and is discovered by chance. Blood picture :- Mild to moderate anemia, raised total leucocyte count and normal or low platelet count. In differential count : 90% or more of circulating leucocytes are mature lymphocytes, less than 10% of lymphocytes are large or prolymphocytes or reticular (transformed) lymphocytes.
27
28
29 CLL B-cell: common T-cell: rare
30 CML Clinical features :- Anemia, Splenomegaly, Fatigue, Weight loss, Minor bruising.
31
32 Chronic Myeloid Leukemia (CML): Typical CML usually occurs between years of age, in children it is called juvenile CML. 95% of patients with typical CML show philadelphia (ph ) chromosome (translocation of 9 and 22 chromosomes) in blood and marrow. Phases of CML 1)Chronic phase 2) Accelerated phase 3) Blastic phase
33 Blood picture :- Moderate anemia Markedly elevated total leuococyte count, increased platelet count. Differential count shows predominantly myelocyte and mature neutrophils, myeloblasts are less than 10%. Basophilia & eosinophilia are frequent. Cytochemistry :- NAP(Neutrophil Alkaline Phosphatase) activity is markedly reduced.
34
35 CML Ph +ve Ph ve, BCR-abl +ve Ph ve, BCR-abl -ve Eosinophilic Leukemia Ph: Philadelphia chromosome BCR: Breakpoint cluster region; abl : Abelson oncogene
36
37 Leukemoid reaction
38 Definition:Extremely high leukocyte counts seen in a non- leukemic state and may be lymphoid or granulocytic in nature Causes: Severe infections Extensive burns Malignancies with bone marrow infiltration Severe hemorrhage Lymphoid reactions seen usually in children in response to viral infections
39 Parameter Leukemoid reaction Leukemia 1. Clinical presentation 2.Examination of blood a Total leukocyte count Features of underlying diseases; fever common <50000/micro lit Slenomegaly Variable, usually > 1 lac / micro lit b Course of neutrophilia c Evidence of infection d Basophilia e Immature cells Disappears with resolution of underlying disease Toxic granules, Dohle Inclusion bodies Absent Few; cells up to myelocyte stage Progressively increased Absent Present Many; cells up to blasts
40 Parameter Leukemoid reaction Leukemia 3. Examination of marrow Myeloid hyperplasia Increased blasts and immature cells of neutrophil sereies; Suppression of other cell lines 4. Clonality Polyclonal Monoclonal 5. Karyotype Normal Abnormal
41
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