Myeloproliferative Diseases (MPDs)

Myeloproliferative Diseases (MPDs)

• Chronic cellular proliferation of 1 or more hematologic cell lines in the peripheral blood, distinct from acute leukemia
• Characterized by overlapping features and progression to one another, and to acute myeloid leukemia (AML)

JAK2 Mutation

• Normally, JAK2 is a switch that tells blood cells to grow
• JAK2 V617F is always "on", leading to uncontrolled cell growth
• Found in 95% of polycythemia vera (PV) patients, 50% of essential thrombocythemia (ET) patients, and 50% of primary myelofibrosis (PMF) patients

Classification of Chronic Myeloproliferative Diseases

• Chronic myelogenous leukemia (CML)
• Polycythemia vera (PV)
• Essential thrombocythemia (ET)
• Chronic idiopathic myelofibrosis (PMF)

Polycythemia Vera (PV)

• Stem cell disorder characterized by proliferation of all hematopoietic cell lines, predominantly erythrocyte series
• Elevated absolute red blood cell mass due to uncontrolled red blood cell production
• Often accompanied by increased white blood cell (myeloid) and platelet (megakaryocytic) production
• Clinical presentation:
  • Symptoms: headache, weakness, dizziness, excessive sweating, pruritus, erythromelalgia
  • Signs: facial plethora, splenomegaly, hepatomegaly
• Investigation: increased WBCs, HGB, platelets, UA, and NAP score, decreased ESR, positive PCR for JAK2 gen
• Diagnostic criteria:
  • Major criteria: HGB > 18.5 g/dL in men and > 16.5 g/dL in women, or other evidence of increased red blood cell volume; presence of JAK2 mutation
  • Minor criteria: bone marrow biopsy showing hypercellularity for age with trilineage growth, serum erythropoietin level below reference range, endogenous erythroid colony formation in vitro

Essential Thrombocythemia (ET)

• Clinical presentation:
  • Asymptomatic (~ 30-50%)
  • Vasomotor symptoms: headache, syncope, atypical chest pain, acral paresthesia, livedo reticularis, and erythromelalgia
  • Thrombosis and hemorrhage occur to various degrees in 5%-25% of patients
• Investigation: thrombocytosis, may be anemia/normal HGB, normal or slightly increased WBCs, increased UA, NAP score, JAK2 gen mutation
• Diagnostic criteria:
  • Platelet count > 450,000
  • Megakaryocytic proliferation with large, mature morphology and with little granulocytic or erythroid expansion
  • Not meeting WHO criteria for CML, PV, PMF, MDS, or other myeloid neoplasm
  • Demonstration of the lack of evidence of a secondary (reactive) thrombocytosis or JAK2 gen mutation
• Treatment:
  • Low-risk patients: phlebotomy to reduce platelet count
  • High-risk patients: cytoreductive therapy to reduce platelet count and prevent thrombosis