1. The acute Leukemias are clonal hematopoietic malignant disease that arise from the malignant T r a n s f o r m a t i o n of an early Hematopoietic stem cell. The acute Leukemia Dr.Azarm

2. Known risk factors for leukemia High dose radiation exposure Occupational exposure to benzene Prior chemotherapy especially alkylating agents Chromosomal instability disorders, such as - Bloom’s syndrome, - Fanconi’s anemia, - Downs syndrome, - Ataxia telangiectasia. Dr.Azarm

3. Acute leukemiais are classified by cell linesge into (1) acute myelogenous leukemia (AML) or (2) acute lymphoblastic leukemia (ALL) based on: - Morphology - Cytogenetics - Cell surface -Cytoplasmic markers -Molecular studies Dr.Azarm

4. Complication of Leukemia -Bone Marrow failure Anemia, Leukopenia, Thrombocytopenia -Infection -Bleeding -Blast infiltration in: Bone Marrow Pripheral Blood Lymph nodes spleen Liver Skin Meningeal Other Organs

5. FAB Classification of acute Leukemia Acute Myeloblastic Leukemia M1- Acute Myeloblastic L. without differentiation M2- A.M.L.with diferentiation (predominantly Myloblast & promyeloblast M3- Acute promyeloblatic leukemia M4- Acute Myelomonocytic leukemia M5- Acute Monocytic Leukemia M6- Erythroleukemia M7- Megakariocytic Leukemia Acute Lymphoblastic Leukemia L1- Small cells,Homogeneous population,childhood variant. L2- Larger L. Heterogeneous population, adult variant L3- Burkitt-like Large cells,Vacuolated cytoplasm

6. Cytogenetics in AML t(15;17) in M3 t(8;21) in M2 Inv(16) in M4 Eo, are associated with better prognosis. Monosomy 7 and multiple breakages, ( poor prognosis ).

7. Investigation and diagnosis FBC and PB film Bone marrow aspiration and biopsy High WBC with Blast, but may be low. Platelet & Hb usually low Marrow with Blast infiltrated >30% Immunophenotyping and Karyotyping allows classification

8. Supportive treatment - Give explanation and offer counselling - RBC and platelet transfusion - Start hydration and Allopurinol Po - Insert tunnelled central venous ccatheter - Start neutropenic regimen and prophylaxis

9. Specific treatment in AML - Treatment protocols are age related; patients. 60y only tolerate less intensive treat and very rarely transplant Supportive treatment alone is a valid treatment option in the >75 age group Outline treatment for patients <60y is 4- 5 courses of intensive combination chemotherapy each 5-10 days with 2- 3 w. Allogeneic or autologous stem cell transplantation are option for younger patients Major complication are infection, Bacterial, Fungal, Viral. In the longer term, relapse is the main complication.

10. Prognosis of AML Worst prognosis group: <10% chance cure: - Age >60y - High WBC - >20% blast after chemotherapy course 1 - CNS disease Good prognosis group : > 60% chance cure: - Young patients<30 - T(15;17) - M3 subtype

11. Treatment plan for ALL 2 phase induction chemotherapy to induce remission 2 or 4 intensification + intrathecal methotrexate or CNS radiation Maintenance therapy for 2 y (out patient oral chemotherapy) Transplant options: - Allogeneic and autologous for child who relapse after CR. Adult in first CR < 60 y especially if philadelphia positive.

12. Prognosis of ALL Childhood ALL has a cure rate of > 70% up to 90% in the best prognostic group ie girls Aged 1- 10y with low WBC, no CNS disease and absence of Ph chromosome who achieve CR after first phase induction chemotherapy.