Handwritten video lecture on Acute Myelogenous Leukemia (AML) and Chronic Myelogenous Leukemia (CML) for the USMLE. Will discuss Pathophysiology, Signs and Symptoms, Treatment and Prognosis
Pathophysiology of Myelogenous Leukemia
The stem cells are found in the bone marrow which gives rise to myeloid stem cells which then give rise to myelobast and then the granulocytes (Eosinophils, Basophils, Neutrophils)
In Acute Myelogenous Luekemia there is an increase in Myeloblasts and may even involve myeloid stem cell which will affect red blood cells and platelets. In Chronic Myelogenous Leukemia there is an increase in Tyrosine Kinase which increases the number of the granulocytes that are found.
ACUTE MYELOGENOUS LUEKEMIA
Arrests at precursor stage with more than 20percent blasts in Bone Marrow. Blasts accumulate in bone marrow and goes to peripheral tissue. Common to have decreased Red Blood Cells and Platelets as Bone marrow gets crowded. Changes in Growth Factor causes arrest of development or decreased apoptosis.
Myelodysplastic syndrome is a minor change in stem cells that is not cancerous yet, but it commonly develops into cancer.
CLASSIFICATION - Currently classification is adopted by WHO which is based on therapeutic targets.
1. AML wiith recurrent abnormalities
a. 8 21 translocation,
b. t(15 17) Promyelocytic Leukemia
i. Auer rods (M3).
ii. PML RaR translocation (may be treated with retinoic acid)
2. AML with Myelodysplastic Syndrome (Poor Prognosis)
3. AML that is therapy related - due to cytotoxic agents
4. AML, not specified - classified from M0 to M7
CLINICAL - Sudden onset also may have thrombocytopenia, anemia, bone main and may affect liver, spleen, lymph node. After treatment patient may experience tumor lysis syndrome (high K, High Uric acid, High Phosphate, Low Calcium)
INVESTIGATIONS - Usually show normocytic anemia and thrombocytopenia. Blood smear shows blasts which are myeloperoxidase positive. Bone marrow aspiration will show hypercellular with more than 20 percent blasts. Cytogenetic analysis help with prognosis.
TREATMENT - Induction consists of 7 days of IV cytarabine with 3 days of short acting anthracycline to kills as much of blasts as possible. Consolidation to mop up left over with high dose cytarabine. If remission favorable and young age then continue more cycles of cytarabine. If no resmission or comorbidities than perform stem cell transplant and investigation therapies.
PROGNOSIS - depends on age. As age increases the prognosis is worse
CHRONIC MYELOGENOUS LUEKEMIA
PATHOGENESIS - Translocation between chromosome 9 (ABL1) and Chromosome 22 (BCL). ABL is responsible for production of tyrosine kinase which is tightly regulated. ABL transfers over to BCL on chromosome 22 known as ABL BCR fusion and the Philadelphia chromosome. This leads to constant production of tyrosine kinase.
CLINICAL - has more insidious onset and found as incidental finding. Chronic phase is symptomatic but can be controlled with treatment. Accelerated phase there is an increase in the number of blasts and will be less responsive to treatment. Final stage is blast crisis is when it transforms to AML with extramedullary syndromes.
INVESTIGATIONS - High level of leukocytosis that are LAP negative to rule out leukemoid reaction. Cytogenetic analysis is diagnostic. Flow cytometry identifies CD Markers present.
TREATMENT - In chronic phase give imatinib meyslete which is a tyrosine kinase inhibitor, but this is not a cure and the disease is always there. Accelerated blast crisis then look for hematopoietic stem cell transplant which is curative. Interferon alpha and Busulfan can be used while waiting for donor.