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20 Cards in this Set
- Front
- Back
Myeloproliferative disorders affect which line of stem cells?
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Myeloid precursor line (giving rise to platelets, monos, PMNs, RBCs)
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General char of Myeloproliferative disorders
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Hepatosplenomegaly (extramedullary hematopoeisis)
Clonal marrow expansion (from single cell that got a key mutation Hypercatabolism (fevers, sweats, weight loss) Predisp to evolve into acute myeloid leuk Loss of control of normal prolif. |
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CML other sx and findings
(chronic myeloid leukemia) |
Early satiety, abdom pain.
Labs - elev WBC, Hgb, platelets. Later will get anemia and thrombocytopenia. Periph smear - immature myeloid cells but few blasts. Leukocyte alkaline phophatase score is low. (normal/high in reactive leukocytosis) BM biopsy - hypercell marrow with inc myeloid/erth ratio. Also more eosinophils. THIS IS THE MAIN WAY TO TELL. t(9;22) must be present. |
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Diff in cells in CML and AML
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CML - increase prolif at each step so there are more cells than normal.
AML - More prolif and a block to differentiation. So there is a build up of blasts with very few of the downstream cells. |
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CML WBC differential characteristics
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Total WBC increased.
WBC have full range of immature myeloid cells. Baso/eosinophils are increased Blasts are usualyl more prominent in AML. |
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CML - Pathogenesis
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The Philadelphia Chromosome (t9;22). bcr-abl transfusion.
Dx by FISH Makes a tyrosine kinase constitutively active (Gleevec targets this). The signal that it sends is very complex |
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CML stages
Chronic |
1.
High counts, splenomegaly. Easily controlled with hydroxyurea (slow down DNA synth). Best results of HSC transplant is in this phase. Median duration is 3 years |
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CML Stages
Accelerated |
2.
Elev WBC more difficult to control. Higher doses of hydroxyurea needed to suppres RBCs and platelets. Spleen begins to increase in size and constitutional symptoms return. Median duration - 1 year |
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CML stages
Blast |
3.
Equiv to acute leukemia. Blast cells may have AML or ALL phenotypes. Unresponsive to typical leukemia therapies and allogeneic HSCTransplant. Survival - 3-6 months. |
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CML tx strategy
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Start gleevec immediately.
monitor resp with FISH for the translocation and RT-PCR and cytogenetics (karyotyping). If response is poor, consider HSCT (but SE and GVHD can be very bad) |
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Polycythemia vera
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Median age 60.
Visual disturbances, thrombosis, puritis, erythromelalgia (itchy?) Plethora-face looks red. Labs - elev Hgb/Hct with or without elev WBC and platelets. Later in disease - anemia and thrombocytopenia. Periph blood smear shows normal cells and erythropoetin is below normal. Molec dx - V617F JAK2 mutation. This is part of the epo signaling pathway and when mutated, it is constitutively active. |
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Dx of polycythemia vera
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No diseases causing secondary erythrocytosis (incl hypoxia, polycythemic disorders, high-affin hemoglobins, tumor causing EPO production).
Incr hemoglobin Low EPO concentration. This is key for polycythemia!!! Presenve of JAK2 mutation BM biopsy will be hypercellular. Prominent erythroid, granulocytic, and megakaryocytic proliferation. |
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Tx of polycythemia vera
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Untreated - 6-9 month (stroke, PE, MI)
Phlebotomy is very useful. Gradually only have to do it 2-4 times a year. Long-term prognosis - Can develop myelofibrosis, secondary AML/MDS. These patients respond poorly to therapy. JAK2 kinase inhibitors may also be helpful in future. THIS IS FAIRLY CURABLE! |
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Essential thrombocythemia - general features
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HA, syncope, visual changes.
Complc - thrombosis, abnormal bleeding Platelet counts high, incr and abn megakaryocytes in BM, no chronic inflammation (i.e. a cause of reactive thrombocytosis), normal iron stores. Note that almost 50% have the V617F JAK2 mutation. |
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CML - Philly chromosome translocation goes away with gleevec?
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yes
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Essential thrombocytopenia therapy and prognosis
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Low risk - No tx neccessary (if <60 y.o., no hisotry of thrombosis and platelets < 1,000,000)
High risk - all others - hydroxyurea (and aspirin and anagrelide is used sometimes) Prognosis - Normal life span with therapy as outlined as above. Small % continue to AML, MDS or myelofibrosis. SO THIS IS FAIRLY TREATABLE. |
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Essential thrombocythemia appearance in BM
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Increased and clustered megakaryocytes in the marrow
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Primary myelofibrosis
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Splenomegaly is the hallmark of this disease (but you see it in lots of other things too)
Labs - Anemia (50% have hgb<10%), teardrop RBCs platelets and wbcs are elevated or decreased megakaryocytes in BM are increased and abnormal Fibrosis due to deposition of collagen in the bone marrow. 50% will have V617F JAK2 mutation (same as polucythemia vera and essential thrombocytosis) |
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Prognosis and therapy of primary myelofibrosis
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Prognosis - based on a point system from cell counts.
Therapy - Allogeneic HSCT can be curative. hydroxyurea can shrink the spleen, transfusions for anemia, splenectomy or splenic irradiation for enlarged spleen. JAK2 kinase inhibitors are showing good results. Causes of death - transformation into MDS or AML, bleeding from low platelets, infection from low WBC. reiterate - it often presents with anemia and has high prob of turning into AML. |
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Tx strategy in general for chronic myeloproliferative disorders
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Always check for CML (t(9;22) because it is very easily and uniquely treatable!!!
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