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What is the definition of leukemia?
- Uncontrolled neoplastic proliferation of one or more of the hematopoietic cell lines
- Abnormal cells found in the bone marrow, peripheral blood, and other hematopoietic organs (liver, spleen, etc)
- Huge number of hematopoietic cells that fail to differentiate and mature
What is the etiology of leukemia? Contributing host factors? Contributing environmental factors?
- Etiology: unknown in most cases
- Contributing host factors
- Heredity (increased incidence in identical twins)
- Congenital chromosomal abnormalities (20-fold increase in Down syndrome)
- Immunodeficiency (Ataxia-telangiectasia, Agammaglobulinemia)
- Chronic marrow dysfunction
- Viruses (HTLV-1, EBV)
- Contributing environmental factors
- Ionizing radiation (Hiroshima/Nagasaki)
- Chemicals (benzene, pesticides)
- Drugs (chloramphenicol, phenylbuazone, and some chemotherapeutic agents)
How many cases of leukemia are diagnosed each year per capita? How many new cases per year? How many deaths per year? Adult to child ratio? Male to female ratio?
- 10 cases per 100,000 persons per year
- 28,700 new cases per year (US)
- 18,100 deaths per year (US)
- 10:1 A:C
- 2:1 M:F
How are leukemias classified (general)?
- Based on cell lineage and maturity
- Acute vs chronic onset (#blasts)
- Myeloid vs lymphoid
Describe the two types of leukemic onset in depth (rate, prognosis, %blasts, further classification)
- Acute: symptoms appear rapidly
- very short life expectancy
- rapid cell proliferation
- >30% blast forms in blood
- FAB classification system
- Chronic: symptoms appear slowly
- several years life expectancy
- gradual cell proliferation
- <10% blast forms in blood
- No specific classification system
Describe the clinical features (symptoms) of acute leukemia
- Leukemic cells can double in <4 days
- Bone marrow failure: leads to bone and joint pain
- Organ infiltration: Splenomegaly and hepatomegaly, Lymphadenopathy, Bleeding gums, mouth lesions, and Neurological symptoms
- Anemia: fatigue, malaise, pallor
- Thrombocytopenia: bruising and bleeding
- Immature cells are functionally challenged (no benefit to the increase)
What does the laboratory evaluation of leukemia consist of (no description, just a list of each aspect)?
- Differential morphology (peripheral blood smear, bone marrow aspirate and biopsy)
- Cytochemistry (special stains)
- Genetic analysis (cytogenetics, molecular)
- Total white blood cell count (leukopenia to leukocytosis)
- RBC indices (typically normocytic/chromic)
- Platelet count (usually decreased)
What are you looking for during a peripheral blood smear screening for leukemia?
- Blasts and other immature cells
- Hypogranular neutrophils
- Nuclear abnormalities
- Acquired Pleger-Huet anomaly (dumbell/round neutrophil nucleus)
- Dyserythropoeisis (decreased production or abnormal morphology RBC)
- Abnormal platelets
What are you looking for during a bone marrow biopsy screening for leukemia? What is normal?
- Marrow cellularity
- Proliferative cell involvement
- >30% blasts and promyelocytes represents leukemia
- 0-5% blasts is normal bone marrow count
- "sheet of cells" often seen due to fast replication
How can you differentiate between the cell lineages in leukemia from blast morphology?
- Myeloblasts: round/oval nucleus
- Fine/delicate chromatin
- cytoplasm is less basophilic, auer rods, primary azurophilic granules
- Lymphoblasts: round/oval nucleus
- Corase chromatin
- cytoplasm is more basophilic, no auer rods or azurophilic granules
What is immunophenotyping? What can it elucidate?
- Method of identifying cells through use of antibodies to cell surface and cytoplasmic proteins
- ID of specific cell types
- Determination of cell differentation
- ID of abnormal cells
What does "CD" stand for? (eg. CD4)
Clusters of Differentiation?
Give general information about the FAB classification system of leukemias w/ subcategories
- Comprehensive morphologic and histochemical classifications
- AML has 7 subgroups (blasts and immature cells are of myeloid or nonlymphoid origin (ANLL)
- M0: acute myeloblastic leukemia without localized differentiation
- M1: acute myeloblastic leukemia without differentiation
- M2: acute myeloblastic leukemia with differentiation
- M3: acute promyeloid/promyelocytic leukemia (M3v)
- M4: acute myelomonocytic leukemia (M4Eo: M4 with bone marrow eosinophilia)
- M5: acute monocytic leukemia (M5a: AMol without differentiation, M5b: AMol with differentiation)
- M6: acute erythroleukemia
- M7: acute megakaryocytic leukemia
- ALL has 3 subgroups (blasts and immature cells are of lymphoid origin (ALL))
- L1: small, uniform lymphoblasts
- L2: large, pleomorphic lymphoblasts
- L3: Brukitt's lymphoma
What is symptom is associated with M3 and M3v leukemias?
hemmorage and disseminated intravascular coagulation