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Myeloproliferative Neoplasms (MPNs)

Christina Snider

Background

  • MPNs = chronic myeloid disorders caused by abnormal proliferation of mature bone marrow cell lineages (granulocytes, erythrocytes, or megakaryocytes)
  • MPNs differ from myelodysplastic syndrome (MDS); cells in MPNs are normally developed (i.e. not dysplastic)
  • Four “classic” MPNs: polycythemia vera, essential thrombocythemia, primary myelofibrosis and chronic myeloid leukemia (CML)

Polycythemia Vera (PV)

Background

  • Polycythemia is a general term: Men = Hb/Hct > 16.5/49%; Women = Hb/Hct > 16/48%
  • Relative polycythemia = Concentrated H/H due to decreased plasma volume
    • Diuretic use, vomiting, diarrhea; H/H should normalize with fluid resuscitation
  • Absolute polycythemia = Increased RBC mass
  • Primary polycythemia: 2/2 Inherited/acquired mutation in RBC progenitor

  • Secondary polycythemia: Increase in RBC mass due to elevated serum EPO

    • Hypoxia/cardiopulmonary associated (chronic pulmonary disease, R-to-L cardiac shunts, sleep apnea, obesity hypoventilation syndrome, chronic carbon monoxide poisoning, including heavy smoking)
    • Kidney associated causes (following renal transplant, renal artery stenosis, hydronephrosis)
    • Autonomous EPO production from an EPO-producing tumors (rare)
    • Steroid Use

  • Epidemiology: Median age of diagnosis is 60 years; 25% cases present at age <50 years.

  • 95% PV pts have JAK2 V617F mutation, but JAK2 V617F mutation is not specific to PV and can be seen in other MPNs

Presentation

  • Incidentally elevated H/H
  • Splenomegaly, generalized pruritus (post-warm bath/shower), unusual thrombosis
  • Erythromelalgia: intermittent occurrence of red, hot, painful extremities

Evaluation

  • CBC with differential and peripheral smear
  • EPO level
  • Rule out secondary causes: Sleep Study, Carboxyhemoglobin, steroids
  • Peripheral blood screen for JAK2 V617F mutation

Management

  • PV treatment aims to prevent thrombosis and bleeding events.
  • Phlebotomy: maintain Hct <45% (One unit 500 mL decreases Hct by 3%)
  • ASA 81 mg for thrombosis prevention and symptom control
  • Hydroxyurea: indicated for high-risk patients (>60 years old or with history of thrombosis)
  • Interferon-alfa, busulfan, or ruxolitinib: indicated in select high-risk patients

Essential thrombocythemia (ET)

Background

  • Clonal stem cell disorder w/ increased platelet counts (>450k/uL)
  • Risks of thrombosis and hemorrhage
  • Median age of diagnosis: 60 years; Twice as common in females.

Presentation

  • Incidental thrombocytosis on CBC
  • Splenomegaly, unusual thrombosis, and erythromelalgia

Evaluation

  • Screen for conditions that cause reactive thrombocytosis: Chronic inflammatory diseases, infections, bleeding/hemolysis, iron deficiency, post splenectomy
  • CBC with smear (platelet anisocytosis) ranging from very small to giant platelets
  • CMP, LDH, Uric Acid, iron studies
  • BCR ABL1 testing should be sent to exclude CML
  • Bone marrow biopsy with staining, cytogenetics, and molecular testing for JAK2, CALR, MPL mutations

Management

  • Avoid ASA 81 in patients with platelet counts >1 million complicated by acquired von Willebrand syndrome due to increased risk of bleeding
Treatment of ET

 Risk Score

(IPSET-thrombosis)

 Features Treatment
High Hx of thrombosis and/or >age 60 with JAK2 V617F mutation Cytoreduction (target plt 100-400k) w/ hydroxyurea, systemic anticoagulation +/-antiplatelet agent
Intermediate Age >60, no JAK2 V617F mutation, no history of thrombosis
Low Age =<60 w/ JAK2 V617F mutation and no history of thrombosis

Observation vs. daily ASA 81

 
Very Low Age =<60, no JAK2 V617F mutation, no history of thrombosis

Primary Myelofibrosis (PMF)

Background

  • Clonal proliferation of myeloid cells with variable morphologic maturity resulting in reactive marrow fibrosis and extramedullary hematopoiesis
  • Least favorable prognosis out of MPN

Presentation

  • Fatigue, weight loss, low grade fever, bone pain, and night sweats
  • Marked splenomegaly ±hepatomegaly (due to extramedullary hematopoiesis)

Evaluation

  • smear: teardrop shaped RBCs (dacrocytes)
  • Bone marrow biopsy: “dry tap” due to extensive reticulin and/or collagen fibrosis mutually exclusive mutations in JAK2, MPL, or CALR

Management

  • Low risk patients: Observe if asymptomatic
  • Cure by allogenic HCT transplantation in young, high-risk patients
  • Treatment of anemias include transfusion support
  • Surgical splenectomy if abdominal pain or transfusion dependent anemia (used very infrequently)

Chronic Myelogenous Leukemia (CML)

Background

  • Definition: MPN characterized by the overproduction of myeloid stem cells that can differentiate
  • Chronic phase:
    • Fatigue, weight loss, bleeding
    • Abdominal fullness and early satiety due to splenomegaly
    • WBC on CBC is typically >100k, and smear shows neutrophilic cells in all stages of maturation with <2% blasts
  • Accelerated phase: Refractory leukocytosis, 10-19% blasts in peripheral blood or bone marrow, worsening peripheral basophilia, thrombocytopenia
  • Blast phase = acute leukemia. >20% blasts in peripheral blood or bone marrow, extramedullary proliferation of blasts

Evaluation

  • Typical findings in blood and bone marrow and confirmation of Philadelphia chromosome (BCR-ABL1 fusion gene) via conventional cytogenetics, FISH, or rt-PCR

Management

  • Hydroxyurea can be used to reduce WBC while awaiting confirmation
  • Oral tyrosine kinase inhibitors (TKIS): Imatinib, dasatinib, nilotinib, and ponatinib
  • Allogenic hematopoietic cell transplantation: Curative option for pts in accelerated and blast phase, as well as young pts w/chronic phase CML who do not respond to TKI therapy
Last update: 2022-06-25 02:05:01