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21 Cards in this Set
- Front
- Back
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General features of myeloproliferative disorders
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Neoplastic event begins at level of pluripotent stem cell
-- each of the major cell lines are involved, some w/ more prolif than others Hallmark is proliferation -- increased, autonomous production of hematopoietic cells -- hypercellular bone marrow Increased cell counts in peripheral blood -- leukocytosis -- thrombocytosis -- polycythemia |
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How are myeloproliferative diseases classified?
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They are classified by cell line:
myeloid --> chronic myelocytic leukemia erythroid --> polycythemia vera megakaryocytic --> essential thrombocythemia "fibroblasts" --> chronic idiopathic myelofibrosis (fibroblasts themselves are not neoplastic, just a prolif of the cell type) |
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What other disorders must we distinguish myeloproliferative d/o's from ?
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MPD must be distinguished from benign cell proliferations that can closely mimic the MPD.
MPD -- has MATURE cells which can disting from benign prolif MPD -- splenomegaly, absolute basophilia, increased serum B12 Clinical presentation is less acute than acute leukemia, and sometimes the pts may be asymptomatic |
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What are the myeloproliferative disorders?
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Chronic Myelocytic Leukemia (CML)
Chronic Idiopathic Myelofibrosis (CIM) Polycythemia Vera Essential Thrombocythemia OTHERS: chronic neutrophilic leukemia chronic eosinophilic leukemia chronic myeloprolif disease, unclassifiable |
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Clinical findings in CML?
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Chronic myelogenous leukemia
Range of incidence is 25-60, byt also accounts for 15% of all leukemias in pediatric age group Symptoms of anemia and hypermetabolism -- weakness, fatigue -- weight loss, anorexia Splenomegaly may be present -- abdominal pain and increasing abdominal girth Pts may be asymptomatic and found to have abnormal cell count on routine lab testing |
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Physical findings in CML?
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May find splenomegaly
May be normal exam |
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Lab findings in CML?
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WBC:
-- markedly elevated, usually >50K, and frequently >100K -- differential shows myeloid precursors including blasts -- absolute basophilia is almost always present RBC: -- usually mild anemia, but may be normal PLATELET COUNT: -- frequently count but may be normal or decreased BONE MARROW: -- nearly 100% cellular (50% is normal for adults) -- predominance of myelopoiesis showing maturation -- ratio of myeloid/erythroid cells is increased, frequently 10:1 (normal is 3:1) LAP: -- markedly decreaseed CYTOGENETICS: -- >90% of cases will have "Philadelphia translocation," t(9;22)(q34;q11.2) involving genes ABL at 9q34 and BCR at 22q11.2 -- BCR/ABL forms new hybrid gene that produces a protein of 210kD size -- t(9;22) is present in all hematopoietic cells excluding a few lymphocytes |
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Prognosis of CML?
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Most patients will succumb to a blast crisis --> a prolif of blasts replacing the maturation in the BM
-- occurs 3-5 yrs after initial presentation -- at time of crisis, additional chrom aberrations can be seen BM transplant is treatment of choice in the chronic phase Some pts will respond to alpha-interferon and show extended remission New therapy w/ Imatinib Mesylate (Gleevec), an inhibitor of specific protein tyrosine kinases, show promise for improved prognosis |
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Differential for CML?
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Leukemoid rxn
Other MPD Chronic myelomonocytic leukemia |
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Clinical findings in CIM?
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Predom older adults >50
May be asymptomatic or present w/ signs/symptoms of anemia and splenomegaly Splenomegaly is part of the disease process due to the myeloid metaplasia **disorder is also called agnogenic myeloid metaplasia, and myelofibrosis w/ myeloid metaplasia (MMM) |
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Lab findings in CIM?
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WBC:
-- usually elevated but <25K -- can be normal or decreased -- Differential shows myeloid cells at all stages of maturation, including blasts and presence of nucleated RBCs (leukoerythroblastosis) RBC: -- anemia is almost always present -- anisopoikilocytosis, especially w/ tear drop shaped cells PLATELETS: -- usually normal or elevated -- large hypogranular -- sometimes circulating micromegakaryocytes BONE MARROW: -- marrow is hypercellular, but w/ a diffuse background fibrosis making it "inaspirable" -- clusters of megakaryocytes seen CYTOGENETICS: -- 50% may have chrom aberrations, but none are diagnostic |
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Prognosis of CIM?
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Pts usually survive 5-10yrs
Approx 10-15% will evolve into blast crisis Most will have gradual replacement of marrow hematopoiesis w/ dense fibrosis and succumb to problems of marrow failure -- severe anemia -- hemorrhage -- infection Treatment is mainly supportive, as no effective "curative" treatment -- BM transplant performed in few cases |
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Differential for CIM?
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"Leukoerythroblastosis"
1. marrow stress --> infection, hemorrhage, hemlolysis 2. myelophthisis --> metastatic tumor or granulomas in BM 3. Other myeloprolif d/o's |
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Clinical findings in polycythemia vera?
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Older adults >50; median age is 60
Signs and symptoms of increased red cell mass: -- plethora -- cyanosis -- HTN -- headaches -- dizziness -- abdom pain Increased blood volume together w/ abnormally fxning platelets leads to problems of thrombosis AND hemorrhage |
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Lab findings in polycythemia vera?
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WBC:
-- usually mildly elevated at time of dx, <25K, but may be normal RBC: -- elevated -- HCT >55% (erythrocytosis) -- normal morphology, unless coincident iron deficiency PLATELETS: -- normal or elevated -- may have abnormal fxn BONE MARROW: -- hypercellular w/ increase of all hematopoietic precursors ERYTHROPOIETIN: -- serum levels DECREASED CYTOGENETICS: -- 50% of cases may show chrom aberrations but none are diagnostic |
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Prognosis of polycythemia vera?
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Pts usually survive 10-15yrs
Approx 5-10% will bave blast crisis Most enter a "spent phase" of marrow failure Treatment aimed at decreasing RBC mass |
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Differential Dx of polycythemia vera?
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RELATIVE POLYCYTHEMIA
-- dehydration -- spurious ABSOLUTE POLYCYTHEMIA Primary: -- Polycythemia Rubra Vera Secondary: Appropriate -- high altitude -- cardio-pulmonary disease -- hemoglobinopathies Inappropriate -- renal cyst -- neoplasms |
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Clinical findings in essential thrombocytopenia?
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Least common -- predominantly older adults
Patients will have problems related to hemorrhage AND thrombosis |
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Lab findings in essential thrombocytopenia?
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WBC:
-- normal or elevated RBC: -- usually mild to moderate anemia PLATELET COUNT: -- >600K and frequently is >1million -- morphology may be normal, or may have some large and or hypogranular platelets BONE MARROW: -- hypercellular w/ increased megakaryocytes -- some may be large w/ immature nuclei -- may be in clusters |
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Prognosis of essential thrombocytopenia?
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Patients are usually older and survival ranges from 10-15yrs
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Differential Dx of essential thrombocytopenia?
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Other causes of thrombocytosis:
-- chronic inflamm D/O's -- TB -- Various neoplasms -- other MPD |
