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41 Cards in this Set
- Front
- Back
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What is acute leukemia?
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Disease of leukocytes and precursors causing immature and abnormal cells
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Where are immature and abnormal leukocytes found in acute leukemia?
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Bone marrow
Peripheral blood Liver Spleen Lymph nodes |
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What causes acute lymphoblastic leukemia?
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Accumulation of lymphoblasts in the bone marrow
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What are the levels of FAB (French American British) classification for lymphoblastic leukemia?
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L1
L2 L3 |
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What stage in the FAB (French American British) classification system is this lymphoblastic leukemia slide and what are the characteristics that assign it to this stage?
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L1:
- Fine chromatin - Small nucleoli - Uniform in size - Little cytoplasm |
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What stage in the FAB (French American British) classification system is this lymphoblastic leukemia slide and what are the characteristics that assign it to this stage?
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L2:
- Variation in nuclear size - Prominent nucleoli - More cytoplasm |
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What stage in the FAB (French American British) classification system is this lymphoblastic leukemia slide and what are the characteristics that assign it to this stage?
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L3:
- Mature chromatin with clumping - Multiple nucleoli - Basophilic and vacuolated cytoplasm |
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What is the current system of classification for lymphoblastic leukemia and by what mechanisms is this done?
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Cell of origin:
- Type of cell of origin via immunophenotype - Cytogenics - Molecular testing |
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What are the two major mechanisms of oncogenesis?
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Loss of function of tumor suppressor genes
Oncogenes from proto-oncogenes |
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What are some genetic factors that are linked to the incidence of lymphoblastic leukemia?
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Down's syndrome
Bone marrow stimulation Chromosomal breaks Immune dysfunction |
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What are some environmental factors that are linked to the incidence of lymphoblastic leukemia?
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Chemicals
Drugs Radiation Infection |
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What are the two major types of cellular pathways in which mutations must occur in order for lymphoblastic leukemia to occur?
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Mutation in proliferation and survival (giving advantage)
Mutation in differentiation (impairing differentiation) |
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What are the three classifications of acute lymphoblastic leukemia?
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Pre-B cell
B cell T cell |
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What are the three most important B cell acute lymphoblastic leukemia gene mutations and what do they do for the cell?
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t(12;21) Tel/AML1
- Increased proliferation t(9;22) BCR-ABL1 - Increased proliferation and survival t(4;11) AF4/MLL - Increased proliferation |
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What is the most frequently mutated tumor suppressor gene in human cancer?
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p53
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How does incidence of acute lymphoblastic leukemia change with age?
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Decreases with age
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What is the peak of incidence for acute lymphoblastic leukemia?
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2-3 years
(secondary peak after 40) |
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What are clinical symptoms of acute lymphoblastic leukemia?
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Bone marrow failure
Organ infiltration |
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What are hematogenous consequences of bone marrow failure?
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Anemia
Neutropenia Thrombocytopenia |
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What common sites of organ infiltration seen in acute lymphoblastic leukemia?
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Lymphadenopathy
Bone marrow enlargement Medaistinal masses CNS infiltration Testicular enlargement |
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What are the diagnostic tests commonly performed for acute lymphoblastic leukemia?
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CBC
Blood smear Bone marrow aspirate CSF sampling Chest X-ray |
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What are diagnostic features of a CBC for acute lymphoblastic leukemia?
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Increased WBC
Decreased Hgb Decreased platelets |
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What is required for a diagnosis of acute lymphoblastic leukemia from a bone marrow aspirate?
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Hypercellular bone marrow with >20% blasts
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What are the qualifications for hyperdiploidy and hypodiploidy and how do these conditions affect prognosis?
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Hyperdiploidy:
- > 50 chromosomes - Good prognosis Hypodiploidy: - <44 chromosomes - Poor prognosis |
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What are common clinical presentations seen with T cell acute lymphoblastic leukemia
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Increased WBC
Pleural effusion Mediastinal masses |
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What is the most common pathway that is activated in T cell acute lymphoblastic leukemia?
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NOTCH pathway
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What are the most common genes that are involved in T cell acute lymphoblastic leukemia?
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TCR genes
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When is acute lymphoblastic leukemia considered to be in remission?
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<5% blasts in bone marrow
Normal peripheral blood count No symptoms or signs of disease |
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What constitutes general supportive therapy for acute lymphoblastic leukemia?
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Central venous line
Blood product support Prevention of tumor lysis syndrome Treatment of infection with prophylactic antibiotics |
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What are consequences of tumor lysis syndrome?
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Increased uric acid
Increased potassium Increased phosphate Renal failure |
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What are the phases of treatment for acute lymphoblastic leukemia?
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1. General supportive therapy throughout
2. Remission induction 3. Intensification / Consolidation 4. CNS directed therapy 5. Maintenance and continuation |
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What is the goal of the remission induction phase for acute lymphoblastic leukemia?
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Rapidly kill most leukemia cells
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What is the goal of the intensification / consolidation phase of treatment for acute lymphoblastic leukemia?
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Reduce tumor burden to very low levels
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What are ways by which CNS directed therapy is administered for the treatment of acute lymphoblastic leukemia?
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Administer chemotherapy directly into CSF
Cranial radiation (high chance of CNS defects) High dose chemotherapy |
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What are some factors involved with maintenance and continuation of treatment for acute lymphoblastic leukemia?
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Daily oral
Weekly injection Steroid pulses for 5 days / month |
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What is minimal residual disease (MRD) in acute lymphoblastic leukemia?
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Presence of a small number of tumor cells even in complete remission
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What is the optimal cutoff for minimal residual disease (MRD) in acute lymphoblastic leukemia?
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.01%
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What is the cure rate of acute lymphoblastic leukemia in children?
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85%
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What is the difference between good risk patients and poor risk patients in acute lymphoblastic leukemia?
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Good risk patients are subjected to less intensive treatment
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What are the mechanisms of relapse for acute lymphoblastic leukemia?
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Sanctuary sites
Leukemic cells remain in G0 Primary resistance Secondary resistance after frontline treatment |
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What are the types of relapse seen in acute lymphoblastic leukemia?
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Isolated bone marrow relapse
Combined relapse Isolated extramedullary relapse |
