PAS 601 Myelodysplastic Syndromes and Myeloproliferative Neoplasms

What are Myelodysplastic Syndromes (MDS)?

Immature blood cells in the bone marrow do not mature or become healthy cells

Who is Myelodysplastic Syndromes (MDS) most common in?

men; 70 years

What is the MCC of Myelodysplastic Syndromes (MDS)?

idiopathic

What defines Myelodysplastic Syndromes (MDS)?

Cytogenetic abnormalities (e.g., deletion of chromosomes 5 or 7 or trisomy 8)

What are the signs and sx of Myelodysplastic Syndromes (MDS)?

- Many patients are asymptomatic

- Depends on the cell type affected (abnormal blood counts)

- Fatigue, infection, bleeding due to bone marrow failure

- Possible splenomegaly

How is Myelodysplastic Syndromes (MDS) dx?

Bone marrow aspiration and biopsy: dysplasia in >10% of cells, may show increase in myeloid blasts (<20%), monocyte precursors, or pathologic ring sideroblasts

How is Myelodysplastic Syndromes (MDS) scored?

International Prognostic Scoring System Molecular (IPSS- M)

What does International Prognostic Scoring System Molecular (IPSS- M) look at for MDS?

percentage of myeloblasts, type and degree of myeloid dysplasia, and presence of ring sideroblasts

How is Myelodysplastic Syndromes (MDS) tx?

supportive care, drug therapy, allogeneic stem cell transplant

What is Myelodysplastic Syndromes (MDS) supportive care?

-Transfusions

-Erythropoiesis-stimulating agents (ESAs) such as epoetin alfa (Epogen) or darbepoetin alfa (Aranesp)

-Myeloid growth factors, like filgrastim

-Thrombopoietin analogs, romiplostim and eltrombopag

-Prophylactic antibiotics

What medications can be prescribed for Myelodysplastic Syndromes (MDS) management?

- Lenalidomide (Revlamid)

- azacitidine (Vidaza)

- decitabine (Dacogen)

What do azacitidine (Vidaza) and decitabine (Dacogen) do?

stimulate maturation of RBCs

What is the only curative tx for Myelodysplastic Syndromes (MDS)?

stem cell transplant

What is prognosis for Myelodysplastic Syndromes (MDS)?

- fatal

- die due to infection

- excess blasts --> higher rate of developing acute leukemia

What are the Myeloproliferative Neoplasms (MPN)?

- Polycythemia Vera

- Essential Thrombocytosis

- Primary Myelofibrosis

What causes Polycythemia Vera?

Janus kinase 2 (JAK2) gene

What is Polycythemia Vera?

Accumulation of phenotypically normal RBCs, granulocytes (neutrophils, eosinophils, basophils), and platelets without a physiologic stimulus

What are signs and sx of Polycythemia Vera?

- Aquagenic pruritus

- Splenomegaly

- Erythromelalgia

- Thrombosis

How is dx of Polycythemia Vera confirmed?

JAK2 mutation screening

When is trilineage growth seen?

Polycythemia Vera

How is Polycythemia Vera tx?

- Phlebotomy

- Hydroxyurea

What is prognosis of Polycythemia Vera?

Indolent disease with median survival of 15 years

What is essential thrombocytosis?

Chronic myeloproliferative neoplasm characterized by increased platelets in circulating blood

Who is essential thrombocytosis most common in?

women

What are signs and sx of essential thrombocytosis?

- most asymptomatic

- thrombosis

- erythromelalgia

What is erythromelalgia?

painful burning of hands and feet with warmth and erythema

How is essential thrombocytosis dx?

CBC: Thrombocytosis* (may be >2,000,000)

How is essential thrombocytosis tx?

- hydroxeurea

- aspirin (prevent thrombosis & tx erythromelalgia)

What is prognosis for essential thrombocytosis?

- Indolent disorder with long term survival (> 15 years)

- Major morbidity - thrombosis

What is Myelofibrosis?

Excessive scar tissue in the bone marrow impairs its ability to produce normal blood cells,

What causes Myelofibrosis?

Genetic mutation (JAK2, CALR, MPL) → abnormal stem cells → produce more mature cells that grow quickly → fibrosis and chronic inflammation

What is the end result of Myelofibrosis?

lack of RBC, abundance of WBC, variable PLT

What is the hallmark sx of Myelofibrosis?

Extramedullary hematopoiesis: splenomegaly, hepatomegaly, lymphadenopathy, or pericardial or pleural effusion

How is Myelofibrosis dx?

- teardrop poikilocytosis

- leucoerythroblastic blood

- giant abnormal platelets

What is seen on BM biopsy for Myelofibrosis?

dry tap

How is Myelofibrosis tx?

- Ruxolitinib (Jakafi) if JAK2 mutation

- blood transfusions for anemia

- hydroxyurea for splenomegaly

What is prognosis for Myelofibrosis?

Median survival from diagnosis is 6-7 years