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