Definition – family of closely related, acquired neoplastic clonal disorders of the hematopoietic stem cell

• characterized by the sustained proliferation of one or more hematopoietic cell lines or increased bone marrow fibrosis.
• Ý # of RBC, WBC, platelets and fibrosis. (maturation is normal)
• etiology unknown, though Ý incidence in populations exposed to radiation and chemicals known to damage DNA.
• the stem cells and their descendants are not under normal physiological controls of hematopoietic cell growth.
• all cell lines (red cells, white cells, and platelets) can be shown to be descendants of a single altered stem cell
• proliferation of one particular cell type dominates and forms the basis of the classification system.
• these syndromes may transform from one to another and have a predisposition to evolve into acute leukemia .

• (1) Chronic Myelogenous Leukemia – CML is the most common of the myeloproliferative disorders. characterized by:
• massive overproduction of slightly defective granulocytes, (presents with Ý WBC count)
• the presence of the Philadelphia chromosome
• inevitable progression to acute leukemia.
• (2) Polycythemia Vera – P. vera (presents with Ý RBC count)
• Characterized by erythrocytosis or the pathological expansion of the red cell mass
• must be distinguished from conditions associated with secondary erythrocytosis due to elevated erythropoieten (EPO)
• chronic hypoxemic states: e.g. abnormal Hgb with Ý O₂ affinity, dehydration with ß plasma volume,
• EPO secreting tumors: e.g. renal cell carcinoma and hepatocellular carcinoma
• diagnostic criteria for primary P. vera: EPO levels must be ß and all 3 Major or First Two Major + 2 Minor are present:
• Major:
• (1) Expansion of RBC mass: Male > 36mL/kg Females > 32ml/kg (adjusted for vol of distribution)
• (2) Normal PO₂ ( Saturation > 92%).
• (3) Splenomegaly,
• Minor:
• (1) leukocytosis: WBC count <12 x 10⁹/L (without fever or infection)
• (2) thrombocytosis, Platelet count > 400 x 10⁹/L
• (3) elevated LAP (leukocyte alkaline phosphatase) (without fever or infection)
• (4) Ý vitamin B₁₂ or vitamin B₁₂ binding capacity.
• Clinical Features – (generally older patients.) Ý Hct and Hgb.
• signs and symptoms result from:
• the expansion of the red cell mass
• Ý blood volume
• hyperviscosity: Þ poor circulation Þ ß O₂ delivery (Affects CNS)
• and/or abnormal platelet function.
• Pt History: may present asymptomatic or present with vague, nonspecific complaints as follows:
• Headaches, dizziness, visual disturbances, and other CNS symptoms.
• Peptic ulcer disease is common
• pruritis occurs in 10% of patients.
• thrombosis (arterial and venous) and hemorrhage are common (major cause of morbidity and mortality)
• 75% of patients may have hemorrhagic or thrombotic complications post-op if P vera is not controlled 1st.
• PE: See table at end for Lab features
• plethora = ruddy cyanosis of face, nose, ears, and lips
• congestion of mucous membranes
• HTN
• moderate splenomegaly (75% of patients) and mild hepatomegaly
• Course and Prognosis - chronic disease with a long and variable natural history.
• median survival after diagnosis is 8-10 years
• anemic spent phase occurs after several years of erythrocytosis
• 5-15% of patients will develop postpolycythemic myelofibrosis
• may signal the transformation to acute leukemia which occurs in 10% of patients
• Causes of death are primarily related to thromboembolic complications and the development of leukemia.
• Treatment – first three of the following are equally effective individually in treating P. vera by have side effects
• (1) Phlebotomy to maintain hematocrit below 46 (increases the risk of thromboembolism) better for someone young
• (2) ³²P
• (3) alkylating agents (increase the risk of leukemia transformation) – better for the elderly
• (4) hydroxyurea: this is the way to go but long term effects are not really known.
• (3) Myelofibrosis (Agnogenic Myeloid Metaplasia)
• Characterized by immature granulocytes and distorted and teardrop shaped RBC in the peripheral blood.
• Splenomegaly
• Ý marrow fibrosis is a hallmark of the disease
• is 2 ^o to the abnormal proliferative stem cell process Þ production of a growth factor Þ Ý in fibroblast.
• Clinical Features – Peak incidence in 6th and 7th decades.
• Patients may be asymptomatic with disease picked up due to splenomegaly or an abnormal peripheral blood smear.
• symptoms of anemia (weakness, fatigue, pallor, exertional dyspnea)
• splenomegaly, (LUQ fullness or pain, early satiety), enlarged in all patients and may be massive
• due to extramedullary hematopoiesis plus a markedly increased blood flow to the spleen.
• Thrombocytopenia with related phenomenon (e.g. bleeding)
• Laboratory Features – See table at end. Peripheral blood differential diagnosis includes infiltrative marrow process: MAI, TB, Metastatic CA, lymphoma, etc. So bone marrow biopsy is indicated:
• hypocellular marrow with increased reticulin
• leukoerythroblastic peripheral blood smear characterized by the presence of immature granulocytes, nucleated red blood cells, and teardrop shaped erythrocytes.
• Course and Prognosis – chronic disease with variable lengths of survival.
• 5 year survival is 60% that of age- and sex-matched controls.
• 5-15% will develop acute leukemia.
• Natural History:The causes of death include thromboembolism, hemorrhage, acute leukemia, and infection.
• Treatment – Supportive observation, transfusions, androgens or steroids for symptomatic anemia;
• splenectomy is indicated for painful splenomegaly, refractory hemolysis, refractory thrombocytopenia, or portal hypertension secondary to the enlarged spleen.
• Chemotherapy (hydroxyurea) or radiation therapy may help control splenomegaly.
• (4) Essential Thrombocythemia (ET): least common of the myeloproliferative disorders
• Characterized by: massive overproduction of platelets.
• must be differentiated from:
• disorders associated with secondary thrombocytosis including severe iron deficiency, nonhematologic malignancies (solid tumors), chronic infections, and collagen vascular disorders.
• P. Vera by the absence of an increased red cell mass
• CML by the absence of the Philadelphia chromosome.
• Ý megakaryocytes in marrow won’t distinguish it from Primary Thrombocythemia.
• Clinical Features – disease of the elderly but does occur in younger people.
• present with anemia, hemorrhage, or thrombosis (bleeding and thrombosis can occur in the same patient.
• splenomegaly is not as pronounced as in the other myeloproliferative disorders because of the common occurrence of splenic vein thrombosis leading to splenic atrophy.
• Laboratory Features – See Figure 2.
• Platelet count usually >1000x10⁹ /1.
• Marrow is hypercellular with megakaryocytic hyperplasia.
• The peripheral smear may show changes secondary to autosplenectomy - Howell Jolly bodies and NRBC.
• Course and Prognosis – Variable, punctuated by episodes of bleeding and thrombosis; 5% transform into another myeloproliferative disorder; 5-10% transform into acute leukemia. 10 year mean survival
• Treatment – Variable depending upon age and clinical features therefore need to individualize for patient
• plateletpheresis to rapidly lower the platelet count if patient has bleeding or thrombosis;
• observation if a symptomatic;
• 32P, alkylating agents, or hydroxyurea for chronic control of thrombocytosis;
• aspirin if thrombotic manifestations predominate; splenectomy is usually contraindicated.
• Anagrelide, is useful in treating the thrombocytosis of ET and other myeloproliferative disorders.