Download to read offline
More Related Content
![urinalysis [Autosaved].pptx how to interpret](https://cdn.slidesharecdn.com/ss_thumbnails/urinalysisautosaved-240319202949-8f13ded4-thumbnail.jpg?width=640&height=640&fit=bounds)
leukemia.pptx
- 1. The Leukemias By Dr CKMwandama Department of Internal medicine, University Teaching Hospital, Lusaka 29/06/17
- 2. Introduction Definition • The wordleukemia literally means “white blood” referring to neoplastic proliferation of white blood cells or leukocytes. • Leukemias are haematologic neoplasms characterized by clonal malignant proliferation of either mature white blood cells or their precursors.
- 3.
- 4.
- 5. Classification of Leukemia •Leukemias are classified as lymphoid or myeloid, depending on the affected progenitor stem cell type. • Leukemias are also classified as acute or chronic depending on the duration of evolution of the disease
- 6. Classification of leukemia Leukaemiasare classified in 4 major types Acute Lymphocytic Leukemia (ALL) Acute Myelogenous Leukemia (AML) Chronic Lymphocytic Leukemia (CLL) Chronic Myelogenous Leukemia (CML)
- 7. Incidence Leukaemia ALL 11% CLL 26% AML 31% CML 15% others 17% CLL -Chronic Lymphocytic ALL - Acute Lymphocytic CML - Chronic Myelogenous AML - Acute Myelogenous
- 8. Classification of leukemias AcuteLeukaemias • In acute leukemias onset of disease is often abrupt, within weeks, and death may occur within weeks to months without treatment. • Typically, leukocyte development halts at the blast phase with most leukocytes undifferentiated or blasts. • In acute leukemia, the WBC may remain low because the cells are halted at the blast stage
- 9. Classification of Leukemias ChronicLeukaemias • Onset is much slower, often over months or years. • The majority of leukocytes are mature • Typically manifest with very high WBC counts
- 10. Pathophysiology of Leukemia Leukemiasappears to result from a combination of factors • genetic predisposition • chromosomal changes • chemical agents(benzene) • chemotherapeutic agents. • radiation • immunocompromise • viruses
- 11.
- 12. Pathophysiology of Leukemias Leukemogenesisis characterized by ; • blockage of cell differentiation • self-sustainable proliferation • abnormal cell cycle progression • impaired apoptosis
- 13. Pathophysiology of Leukemia Geneticabnormalities identified in the propagation of leukemogenesis include chromosomal translocations gene deletions Amplifications point mutations
- 14. Pathophysiology of Leukemia Proto-oncogenesassociated with leukemogenesis include ABL-Chronic myeloid leukemia N- Ras-Haematologic Malignancies FMS-Leukemia c-MYC- Burkitts Leukemia
- 15. Acute Lymphoblastic Leukemia Characterized by presence of lymphoblasts in the bone marrow, peripheral blood ,liver, spleen, lymph nodes and soft tissues Philadelphia chromosome positive(t9:22 translocation) Classified into 3 stages • L1: Small homogeneous blasts; mostly in children • L2: Large heterogeneous blasts; mostly in adults • L3: “Burkitt” large basophilic B-cell blasts with vacuoles
- 16. Acute Myeloid Leukemia Characterizedby uncontrolled proliferation of myeloblasts, hyperplasia of bone marrow and spleen FAB Classification • M0 -- Undifferentiated AML • M1 -- AML without maturation • M2 -- AML with maturation • M3 -- Acute Promyelocytic Leukemia • M4 -- Acute Myelomonocytic Leukemia • M5 -- Acute Monocytic Leukemia • M6 -- Erythroleukemia (DiGuglielmo’s) • M7 -- Megakaryoblastic Leukemia
- 17. Acute Myeloid Leukemia WHOclassification • AML with recurrent cytogenic translocations • AML with multi-lineage dysplasia • AML and myelodysplasia, therapy related • AML, not otherwise categorized
- 18. Chronic Myeloid leukemia DiseaseProgression Estimated Survival Chronic Phase (CP) Accelerated Phase (AP) Blast Crisis (BC) 3 - 5 years 6 - 12 months 3 - 6 months
- 19. Chronic myeloid Leukemia •Characterized by excessive development of mature neoplastic granulocytes in the bone marrow and peripheral blood • Ultimately infiltration into the liver and spleen • Philadelphia chromosome(Ph) is present in up to 95% of patients • Characterized by reciprocal translocation of long arm of chromosomes 22 and chromosome 9 • Ph chromosome is almost specific to CML
- 20. Chronic myeloid Leukemia •Abelson proto-oncogene (c-ABL) come into juxtaposition with the “break point cluster region”(BCR) producing the BCR-ABL fusion oncogene • Resultant oncoprotein is a hyperactive tyrosine kinase • Ph chromosome is also seen in ALL and chronic neutrophilic leukemia
- 21. Chronic Lymphocytic Leukemia •Exclusive in elderly • Hyper-mature lymphocytes with highly condensed nuclei • Massive splenomegaly and Lymph node enlargement is noticeable throughout the body
- 22. Chronic Lymphocytic Leukemia CLLis staged as follows Stage 0-Absolute lymphocyte count >15 000 Stage 1-Absolute lymphocytosis with lymphadenopathy Stage 2-Absolute lymphocytosis with lymphadenopathy with hepatomegaly and or splenomegaly Stage 3-Absolute lymphocytosis with lymphadenopathy with hepatomegaly and or splenomegaly plus anaemia(Hb <11) Stage 4-Absolute lymphocytosis with lymphadenopathy with hepatomegaly and or splenomegaly plus thrombocytopenia(platelet count < 100 000)
- 23. Overall clinical features BoneMarrow Failure Anemia Neutropenia Thrombocytopenia Infiltration Leukemia meningitis Hepatosplenomegaly Central nerve palsy Granulocytic sarcoma Leukemic orchitis Lymphadenopathy Hyperleukocytosis Central nervous system leukostasis/stroke Respiratory distress syndrome Metabolic Hypercalcemia Hyperphosphatemia Hyperkalemia Hypercoagulation Hyperuricemia Weight loss
- 24. Overall Clinical features ALLAML CLL CML Signs/Symptoms Fatigue, weight loss, night sweats, bruising, bleeding Fatigue, weight loss, night sweats White blood cell High/low High/low High High Hemoglobin Normal/low Normal/low Normal/low Normal Platelets Low Low Normal/high Normal/high BM Blasts > 20% > 20% None 0-10% Chronic Phase Spleen/Liver May be enlarged Normal May be enlarged May be enlarged
- 25. Approach to Diagnosis •Medical history and physical • CBC with differential • Bone marrow biopsy and aspiration • Chemistry panel • Cytogenetics • Immunophenotyping
- 26. Treatment of AcuteLeukemia Goals of treatment are as follows Induction therapy Rapidly achieve complete response (CR) Consolidation therapy Maintain CR Eliminate clinically undetectable leukemia Prevent/delay relapse Maintenance therapy Eliminate residual leukemia Prolong remission CNS therapy Prevent relapse
- 27. Chemotherapy for AcuteLeukemias ALL AML Class Agents Class Agents Vinca Alkaloids Vincristine Anthracyclines Daunorubicin Idarubicin Corticosteroids Dexamethasone Prednisone Pyrimidine Analog Cytarabine Anthracyclines Doxorubicin Daunorubicin Antimetabolite Hydroxyurea Antimetabolite Methotrexate Alkylator Cyclophosphamide Enzyme L- Asparaginase
- 28. Chemotherapy for ChronicLeukemia CLL CML Class Agents Class Agents Purine analog Fludarabine Tyrosine kinase inhibitors Imatinib, Dasatinib Nilotinib Steroids Methylprednisolone Alkylators Cyclophosphamide, Chlorambucil, Bendamustine Monoclonal antibodies Rituximab, Alemtuzumab, Ofatumumab
- 29. Bone Marrow /Stemcell transplant Goals of this therapy are as follows • Total myelosuppression of patient’s neoplastic BM • Transplant an HLA-matched BM from any of the following • Patient’s own stem cells removed before • Identical twin • Sibling • Volunteer
- 30. Supportive care • Isolationwith total barrier nursing • Blood and platelets transfusion • Antibiotic cover • G-CSF • Anti-emetics • Prevention of tumor lysis syndrome
- 31. References • Oxford Handbookof Clinical Haematology, 2nd Edition • Oxford Handbook of Clinical Medicine, 9th Edition
- 32.