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60 Cards in this Set
- Front
- Back
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What is leukaemia?
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Accumulation of malignant white cells in the bone marrow and blood
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What are the four types of leukemias?
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Acute lymphoid leukemia (ALL)
Acute myeloid leukemia (AML) Chronic lymphocytic leukemia (CLL) Chronic myelogenous leukemia (CML) |
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What is a blast cell?
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Early hematopoietic progenitor cell
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What is acute myeloid leukemia?
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Rapid abnormal proliferation of hematopoietic progenitor cell with a block in differentiation
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What is key factor in the diagnosis of acute leukemia?
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Blasts must account for > 20% of bone marrow
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What are leukemic stem cells?
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Small subset of stem cells that can give rise to more differentiated blasts
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How do leukemic stem cells and their progeny respond to chemotherapy?
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Generally resistant to chemotherapy
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In what age population is acute myeloid leukemia most prevalent?
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Elderly (~ 65 median onset)
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What are risk factors for acute myeloid leukemia?
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Radiation
Chemotherapy Cigarette smoke (benzene) Genetic predisposition - Down syndrome Chronic or pre-malignant conditions - Myelodysplasia - Myeloproliferative diseases |
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What is leukostasis?
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Intravascular leukocyte aggregation and clumping
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How is leukostasis treated?
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Hydration
Leukopheresis Immediate chemotherapy |
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How does acute myeloid leukemia present clinically?
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High or low white blood cell count
Anemia Thrombocytopenia Tissue infiltration of blasts Diffuse intravascular coagulation |
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Why is infection especially prevalent in acute myeloid leukemia?
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Low white blood cell count
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What is petechia?
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Spontaenous bleeding at points of pressure due to thrombocytopenia
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What are the most common sites of tissue infiltration of blast cells?
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Gums
Skin Brain |
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What is a chloroma?
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Accumulation of blasts causing a tumor-like growth
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Why can acute myeloid leukemia result in diffuse intravascular coagulation and how is it treated?
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Clotting cascade initiated from dying blasts, depleting platelets and other clotting factors
Treat with replacement of clotting factors |
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On what was the French American British (FAB) AML classification system based?
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Morphology
Markers |
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What results from transforming mutations in committed hematopoietic progenitors?
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Blocked differentiation
Retained characteristics of specific progenitor |
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What are the physical diagnostic measures taken for acute myeloid leukemia?
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Bone marrow biopsy and aspirate
Peripheral blood Tissue biopsy (from suspicious tissue) CSF (if symptomatic) |
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From where is the bone marrow biopsy and aspirate taken when diagnosing acute myeloid leukemia?
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Posterior, superior iliac crest
- 2 needles |
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What kinds of diagnostic tests are done from blood and tissue samples when testing for acute myeloid leukemia?
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Morphologic stains
Cytochemistry Imminophenotypic markers Molecular probes RT-PCR |
What are these cellular characteristics and of what are they a diagnostic component?
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Auer rods
- Precipitations of acute myeloid leukemic granules Diagnostic of acute myeloid leukemia |
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What are the immunophenotypic methods of diagnosis when diagnosing acute myeloid leukemia?
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Flow cytometry
Immunoperoxidase assays |
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What are the most common markers in acute myeloid leukemia?
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CD34
CD13 CD33 CD117 |
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What type of genetic analysis is done when diagnosing acute myeloid leukemia?
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Karyotyping for detection of genetic mutation
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What molecular probe mechanism is used when diagnosing acute myeloid leukemia?
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FISH
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What does RT-PCR do?
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Detects translocated product mRNA
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How does the World Health Organization organize subtypes of acute myeloid leukemia?
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Genetic features
Prognostic features |
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What is a myeloid sarcoma?
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Solid, extra-medullary mass of AML blasts
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What are new techniques for classifying ambiguous leukemias?
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Global gene expression analysis
High through-put sequencing |
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What does high through-put sequencing help identify?
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Characterized and new mutations
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What are the favorable prognostic mutations for acute myeloid leukemia?
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t(8;21)
inv(16) t(15;17) NPM1C CEBPA |
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What are poor prognostic mutations for acute myeloid leukemia?
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FLT3ITD
> 3 chromosomal abnormalities t(9;22) t(6;11) t(10;11) del 5 del 7 |
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What is the prognosis for remission of acute myeloid leukemia post-initial induction chemotherapy?
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Good
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What is the prognosis for down-syndrome related acute myeloid leukemia?
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Good
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What is the prognosis for persistent leukemia after initial induction chemotherapy?
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Bad
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What is the prognosis for acute myeloid leukemia with increasing age?
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Bad
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What is the prognosis for acute myeloid leukemia with secondary myelodysplastic changes?
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Bad
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What is the prognosis for therapy-related acute myeloid leukemia?
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Bad
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How is acute myeloid leukemia typically treated?
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Supportive care
Induction chemotherapy |
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What constitutes supportive care for patients with acute myeloid leukemia?
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Replace blood products
- Platelets - Clotting factors Hydration Preventing infection - Antibioitics |
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How is acute myeloid leukemia usually treated in elderly patients?
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Supportive care
Palliative chemotherapy (as opposed to induction chemotherapy) |
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What does induction chemotherapy do?
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Inhibits DNA synthesis and replication causing:
- Apoptosis - Cellular arrest |
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What are the steps in a regimen of induction chemotherapy?
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1. Ara-C + anthracycline
2. Consolidation chemotherapy (Ara-C) 3. Either more consolidation or stem cell transplant depending prognostic features and patient fitness |
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What causes acute promyelocytic leukemia?
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Translocation
- t(15;17)(q22;q12) Fusion of PML and RARα |
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In what age population is acute promyelocytic leukemia especially prevalent?
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Younger patients
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What is there a secondary risk of in acute promyelocytic leukemia
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Diffuse intravascular coagulation
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How is acute promyelocytic leukemia treated?
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All-trans retinoic acid (ATRA)
with anthracyclines |
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What is the cure rate for acute promyelocytic leukemia?
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~ 90%
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What is the risk of treatment of acute promyelocytic leukemia with all-trans retinoic acid (ATRA)?
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ATRA / differentiation syndrome
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What are side affects of treatment for acute myeloid leukemia?
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Acute tumor lysis syndrome
Pancytopenia Mucositis Nausea and vomiting Cardiac toxicity Cerebellar toxicity Palmar-plantar erythrodysthesia Conjunctivitis |
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What is acute tumor lysis syndrome?
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Rapid death and breakdown of leukemia cells during chemotherapy
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What are the symptoms of acute tumor lysis syndrome?
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PUCK:
- Hyperphosphatemia - Hyperuricemia - Hypocalcemia - Hyperkalemia |
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What can hyperuricemia cause in acute tumor lysis syndrome?
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Renal failure
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What can hyperkalemia cause in acute tumor lysis syndrome
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Cardiac dysrhythmia
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How is acute tumor lysis syndrome treated?
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Hydration
Alkalinization of urine Rasburicase (if refractory condition) |
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What part of acute myeloid leukemia treatment is cardiotoxic?
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Anthracyclines
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What part of acute myeloid leukemia treatment causes cerebellar toxicity, palmar-plantar erythrodysthesia, and conjunctivitis?
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Ara-C
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In what direction are future therapies towards acute myeloid leukemia going?
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Specific targeting of pathways required by leukemic cells (as opposed to cytotoxic chemotherapy)
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