Acute Lymphocytic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) for USMLE

Handwritten video lecture on Acute Lymphocytic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) for the USMLE. Discussing Pathognesis, Pathophysiology, Clinical Signs and Symptoms, Labs, Management.
PATHOGENESIS
As the blast cells progress through development stages, there is a mutation that prevents continuation of the next stage leading to a clonal expansion of progenitors.
In Chronic Lymphocytic Leukemia (CLL) problem will occur immediately before plasma cells, so there is high levels of B Cells without plasma cells. Acute Lymphocytic Leukemia can occur in any stage before B cell.
PATHOPHYSIOLOGY - after blockage there will be accumulation in the bone marrow that pushes out all the other cells leading to bone marrow failure. Eventually peripheral blood will have leukocytosis and it may metastasis to CNS, Testes.
ACUTE LYMPHOBLASTIC LEUKEIMIA (ALL)
Usually occurs in children less than 15. May be caused by anti-neoplastic drugs, benzene radiation, Hodgkin’s Lymphoma, Multiple Myeloma, Down’as Syndrome, Wiskott Aldrich Syndrom, and Ataxia Telangiectasia.
CLINICAL - Abrupt onset. Anemia, thrombocytopenia, and decrease immunity. Bone pain due to expansion of the bone marrow diagnosed as arthritis and present as limping. Mediatstinal mass shows up in T cell Leukemias. May lead to respiratory distress and stridor.
Metastasis is usually to liver, spleen, Lymph Nodes, CNS, and testes.
LABS - 10,000 to 100,000 WBC primarily lymphoblasts. Normocytic or Macrocytic Anemia and low folate and thrombocytopenia less than 100,000. Bone marrow hypercellular with more than 25 percent lymphoblasts and completely replaces the bone. Positive for Tdt and CALLA or CD10 positive. T Cell is CD 10 negative.
MANAGEMENT - Chemotherapy in three stages. Induction for remission of less than 5% blasts or normal CBC. Use glucocorticoids, vincristine and asparaginase. In consolidation phase to remove resistant cells by using cyclophosphamide, cytarabine and 6-mercaptopurine. In maintenance phase trying to prevent relapse and recurrence by give intrathecal methotrexate every 3 months as well as cranial irradiation. Then weekly methotrexate, daily 6 mercaptopurine, vincristine and steroid pulse every 1-3 months.
TUMOR LYSIS SYNDROME - increase cell death leads to increase uric acid, potassium, and lowers calcium which leads to renal failure. May be prevented by giving IV fluid double maintenance. Sodium Bicarbonate alkaline urine and dissolve uric acid. Allopurinal decrease uric acid and resburicase.
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Usually found in elderly and peaks at age of 65
CLINICAL - Insiduous onset usually incidental finding on CBC or painless LN. May be associated with autoimmune conditions such as Cold (IgM) and Warm (IgG) pemphigus, ITP, Coomb’s Positive, Neuropathy. Reiter’s transformation is sudden aggrest Large B Cel Leukemia with B symptoms associated with sudden enlarged lymph node, malaise, fever and night sweats. Associated with very poor prognosis.
LAB - usually there is no immunoglobulins, less than 10percent lymphoblasts. Positive for B cell markers CD5 which is known as abberant T Cell marker. Blood smear shows smudge cells.
STAGING - Staged by the Rai Sawitsky system has Low stage, lymphocytosis, Intermediate Stage includes lymphadenopathy and hepatosplenomegaly, and High Stage has anemia and thrombocytopenia. In the Binet staging system group A has hemoglobin greater than 10 and platelet greater than 100,000 and less than 3 lymph nodes are involved. In group B greater than 3 lymph nodes are involved and in stage C less than 10 hemoglobin and less than 100,000 platelets.
MANAGEMENT - Not as responsive to chemotherapy because growing slowly. Wait until disease is advanced. Nucleoside analog for indolent lymphoid malignancy, such as fludarabine, cladiribine, pentostatin and monoclonal antibodies alentuzumab. Allogeniec Stem Cell Transplant is potentially curative.