acute lymphoblastic leukemia ppt presentation

acute lymphoblastic leukemia

1. ACUTE LYMPHOBLASTIC LEUKEMIA LEUKEMIAS

2. Acute Lymphoblastic Leukemia /Lymphoma ALLs are neoplasms composed of immature B (pre-B) or T (pre-T) cells, which are referred to as lymphoblasts .

3. Acute lymphoblastic leukemia Primarily a disease of children Age - Majority occur between 1-5 yrs ( second peak in adults between 30-40 yrs ) B cell ALL – age of 3 T cell ALL - adolescence Sex - Slight male preponderance 75-80% are B-lineage; 20-25% T-lineage MC extra medullary sites of involvement in B-ALL - skin, soft tissue, lymph nodes & bone Mediastinal involvement is common in T-ALL

4. ACUTE LYMPHOBLASTIC LEUKEMIA Predisposing factors for ALL

5. PATHOGENESIS Many of the chromosomal aberrations seen in ALL dysregulate the expression and function of transcription factors that are required for normal B- and T-cell development . B-ALLs have loss-of-function mutations in genes that are required for B-cell development, such as PAX5 , E2A , and EBF , or a balanced t(12;21) involving the genes TEL and AML1 , two genes that are needed in very early hematopoietic precursors

6. CLINICAL FEATURES     •    Abrupt stormy onset    •    Symptoms related to depression of marrow function , including fatigue due to anemia; fever, reflecting infections secondary to neutropenia ; and bleeding due to thrombocytopenia     •    Mass effects caused by neoplastic infiltration , Bone pain resulting from marrow expansion and infiltration of the subperiosteum ; Generalized lymphadenopathy , Splenomegaly , and hepatomegaly ; Testicular enlargement;    •    Central nervous system manifestations such as headache, vomiting, and nerve palsies resulting from meningeal spread.

7. CLASSIFICATION FAB -3 types L-1: 80%-HOMOGENOUS SMALL SIZE L-2: 20%-HETEROGENOUS L-3: 1-2%-HOMOGENOUS LARGE WITH VACUOLATION WHO Precursor B –ALL Precursor T-ALL Burkitt lymphoma in leukemic phase

8. FAB Classification of ALL

9. Acute lymphoblastic leukemia – L 1

10. Acute lymphoblastic leukemia – L1

11. ACUTE LYMPHOBLASTIC LEUKEMIA –L2

12. ACUTE LYMPHOBLASTIC LEUKEMIA – FAB CLASSIFICATION

13. WHO Classification of ALL

14. ACUTE LYMPHOBLASTIC LEUKEMIA B –CELL ALL T- CELL ALL Arise from bone marrow precursor B cell Precursor T cell (often thymic origin) Most common in children Most common in adolescent males Diverse chromosomal translocations Mutations affecting genes like PAX5, TCF3, ETV6 and RUNX1 ( all of which are required for early hematopoietic precursor) Diverse chromosomal translocations NOTCH 1 mutations (50 to 70 %) Hyperploidy (>50 chromosomes) Different translocations Pathogenesis

15. MORPHOLOGY The tumor cells have scant basophilic cytoplasm and nuclei somewhat larger than those of small lymphocytes . The nuclear chromatin is coarse and nucleoli are either absent or inconspicuous. In many cases the nuclear membrane is deeply subdivided, imparting a convoluted appearance. Absence of granules / auer rods.

16. ACUTE LYMPHOBLASTIC LEUKEMIA – L1

17. 1. Blood examination – anemia – thrombocytopenia – variable leukocyte count, usually increased - blood morphology: presence of blast cells 2. Bone marrow morphology - presence of blast cells - suppression of normal hematopoiesis

18. ACUTE LYMPHOBLASTIC LEUKEMIA PERIPHERAL SMEAR Accumulation of neoplastic blasts in marrow suppresses normal hematopoiesis RBC: Moderate to severe anemia WBC: Markedly increased , >20% lymphoblasts Subleukemic / Aleukemic ALL - Some Patients present with pancytopenia with few/no blasts in peripheral blood Lymphoblast morphology : Large Nucleus with condensed chromatin Inconspicuous nucleoli Scant cytoplasm without granules Platelets : Moderate to severe thrombocytopenia

19. ACUTE LYMPHOBLASTIC LEUKEMIA MORPHOLOGY Bone marrow - hypercellular and packed with lymphoblasts which replace normal marrow elements T cell ALL – present with mediastinal masses in 50 to 70% of cells and also associated with lymphadenopathy and splenomegaly Tumor cells – scant basophilic cytoplasm and nuclei is somewhat larger than those of small lymphocytes Nuclear chromatin – delicate, finely stippled and nucleoli are often small and demarcated by rim of condensed chromatin Nuclear membrane is deeply subdivided imparting it convoluted appearance Interspersed macrophages ingesting apoptotic tumor cells gives it “starry sky appearance”

20. 3. Cytochemical stains 4 . Immunophenotyping 5 . Cytogenetics 6. Molecular studies

21. ACUTE LYMPHOBLASTIC LEUKEMIA Cytochemical stains : Myeloperoxidase & Sudan Black : Negative Periodic acid schiff (PAS) : Block Positivity Acid phosphatase : Positive in T-ALL

22. ALL CYTOCHEMISTRY Acid phosphatase T lymphocytes have a high levels of acid phosphatase & can be used to help make a diagnosis of acute T-lymphocytic leukemia

23. Tdt , a specialized DNA polymerase is positive in > 95 % cases of pre-B & pre-T lymphoblasts Primary B-cell ALL : CD10 (CALLA), CD19, CD20, CD79a, HLA-DR, PAX5 Primary T-cell ALL : CD1,CD2, CD5, CD7 & CD99 ALL- Immunophenotyping

24.                                                                  Blood smears, cytology of acute leukemia, AML vs. ALL

25. POOR PROGNOSTIC FACTORS Age under 2 Presentation in adolescence or adulthood; Peripheral blood blast counts greater than 100,000 , which probably reflects a high tumor burden; and The presence of particular cytogenetic aberrations such as the t(9;22) (the Philadelphia chromosome) .

26. GOOD PROGNOSTIC FACTORS An age of 2 to 10 years, A low white cell count, Hyperploidy , Trisomy Of Chromosomes 4, 7, And 10, And The presence of a t(12;21)

27. Differences Parameter ALL AML 1.Age More common in children More common in infants, adolescents & adults 2.LN involvement Common Uncommon 3.Meningeal disease -Bone tenderness -Testicular involement More common Less common 4. Mediastinal l/a Seen in T-ALL rare 5.Morphology of blasts size Cytoplasm Auer rod Nuclear chromatin nucleoli Lymphoblasts Small to medium Scanty Absent Coarse Indistinct,0-2 Myeloblasts Large Moderately abundant Present Fine Prominent ,1-4 6. Myelodysplasia Absent May be present 7.Cytochemistry Myeloperoxidase PAS Negative Block-like positive Positive Diffuse

28. Differences Parameter ALL AML 7.Cytochemistry Myeloperoxidase PAS Negative Block-like positive Positive Diffuse