Myeloproliferative Disorders (MPD) Flashcards
What are MPDs?
Myeloproliferative disorders
- neoplasm of mature myeloid cells (occasionally lymphoid cells)
- leukocytosis with bone marrow hypercellularity
- commonly associated with mutated tyrosine kinases
- frequent extramedullary hematopoiesis
*can progress to AML or ALL*
What are the main types of MPD?
- CML, chronic myeloid leukemia
- PV, polycythemia vera
- ET, essential thrombocythemia
- primary myelofibrosis
What is CML?
Chronic myeloid leukemia (MPD)
- neoplasm of mature myeloid cells (particularly granulocytes)
- caused by t(9;22)/Philadelphia chromosome with BCR-ABL fusion product
- splenomegaly due to extramedullary hematopoeisis
What is the common presentation of CML?
- typically adults (median 50-60); can occur in all ages
- more frequent in men
- fatigue, weakness, weight loss (due to anemia and hypermetabolism)
- splenomegaly causing possible LUQ pain
What are possible complications of CML?
- splenic rupture
- progression to acute leukemia
- hyperuricemia/gout from purine degradation due to high cell turnover (give allopurinol)
- marrow fibrosis
What is the course/prognosis for CML?
-insidious course
- slow progression for ~3 years followed by accelerating phase for 0.5-1 years, and blast crisis (resmbling acute leukemia)
- if treated early, good prognosis with 90% remission (imatinib, tyrosine kinase inhibitor treatment)
How can CML be differentiated from a leukemoid reaction?
Both have leukocytosis and a left shift
CML has:
- increased basophils not present w/ leukemoid reaction
- negative leukocyte alkaline phosphatase (LAP) whcih is positive in leukemoid reaction
- pressence of Philadelphia chromosome
What is PV?
Polycythemia vera (MPD)
- neoplasm of mature myeloid cells (particularly erythrocytes)
- Jak2 kinase mutation
- low serum erythropoietin
- elevated hematocrit -> increased viscosity
What is the common presentation of PV?
-late middle age adults
-symptoms due to inceased blood viscosity
-cyanosis
-facial flushing
- blurry vision and HA
- MI, CVA, and DVT (presenting s/x 25% of cases)
- DVT in hepatic vein is common -> Budd-Chiari syndrome
- hemorrhage
-pruritis, frequent after bathing, from increased histamine release
What are possible complications of PV?
- MI, CVA, and DVT
- DVT in hepatic vein is common -> Budd-Chiari syndrome
-hemorrhage
-hyperuricemia/gout from purine degradation due to high cell turnover (give allopurinol)
- progression to myelofibrosis following treatment (15-20%)
- progression to AML (2%)
What is the course/prognosis for PV?
- insidious course
- good prognosis w/ treatment (median 10 years) (phlebotomy to reduce RBC mass)
- w/o treatment death within months
What is ET?
Essential thrombocytosis _(_MPD)
-neoplasm of platelets
-very little elevation of RBCs or WBCs
-no marrow fibrosis
-Jak2 kinase mutation (50%) or MPL mutation (5-10%)
What is the common presesntation of ET?
- primarily adults >60; can occur in younger ages
- symptoms limited and related to thrombosis or bleeding
What are possible complications of ET?
- MI/DVT
- portal vein thrombosis
- hemorrhage
- erythromelalgia (throbing/burning in hands in feet due to arteriole obstruction by platelets)
What is the course/prognosis of ET?
-indolent course with indisious onset
-asymptomatic periods interupted by occasional hemorragic/thrombotic crisis
-good prognosis (median survival 12-15 years) (“gentle” chemotherapy)
How is ET diagnosed?
Diagnosis of exclussion
Should rule out:
- PCV
- primary myelofibrosis
- reactive thrombocytosis
- iron deficiency anemia
How is ET different from CML, PV, and myelofibrosis?
- rarely progresses to AML
- minimal fibrosis
- no risk of hyperuricemia/gout (megakaryocytes do not lose nuclei when producing platelets)
What is primary myelofibrosis?
Primary myelofibrosis (MPD)
- neoplasm of mature myeloid cells (particularly megakaryocytes)
- Jak2 kinase mutation (50-60%) or MPL mutation (1-5%)
- megakaryocytes produce PDGF and TGF which attracts nomral fibroblasts
- progressive obliterative marrow fibrosis resulting in eventual cytopenias
-extramedullary hematopoiesis w/ splenomegaly
What is the common presentation of primary myelofibrosis?
- primarily adults >60
- splenomegaly (sometimes only finding)
- fatigue (anemia)
What histologic features are present in primary myleofibrosis?
- tear drop RBCs
- nucleated RBCs
- immautre granulocytes
What is the course/prognosis of primary myelofibrosis?
- difficult to treat (median survivial 3-5 years)
- better in younger individuals who can withstand HSCT
What are possible complications of primary myelofibrosis?
- progression to AML (5-20%)
- infections
- thrombosis
- hemorrhage
- hyperuricemia/gout from purine degradation due to high cell turnover (give allopurinol)
What lab findings are expected with CML?
Blood:
- leukocytosis often >100,000 cells/cm3 (primarily granuloytes)
- blasts present
- markedly increased platelets
Bone marrow:
- hypercellular
- sea-blue histocytes
What lab findings are expected with PV?
Blood:
- elevated hematocrit (>60%)
- normal to elevated hemoglobin (14-28g/dL)
- leukocytosis 12,000-50,000 cells/mm3
- increased platelets
Bone marrow:
- hypercellular (early); fibrotic (spent phase)
- increased progenitors (erythropoietic and granulocytic)(early); decreased (spent phase)
What lab findings are expected with primary myelofibrosis?
Blood:
- moderate to severe normochromic, normocytic anemia
- blasts present
- inintial markedly increased WBC; normal to decreased WBC (late)
- normal to elevated platelet count; eventual thrombocytopenia
Bone marrow:
- hypercellular (early); hypocellular (late)
- fibrotic (late)
