MDS and Myeloproliferative DSA

Question 1

Myelodysplastic syndromes- essential of dx

Answer 1

• cytopenias with a hypercellular bone marrow

- morphologic abnormalities in 2 or more hematopoietic cell lines

Question 2

Myelodysplastic syndromes- general

Answer 2

• may evolve into AML
• 5q– refractory anemia (without excess BM blasts)
• refractory anemia with excess blasts
• chronic myelomonocytic leukemia (CMML)- prolif syndrome (monocytosis > 1000)

Question 3

Myelodysplastic syndromes- signs and sx

Answer 3

• > 60 yo
• asymptomatic when dx made
• fatigue, infection, bleeding- BM failure

Question 4

Myelodysplastic syndromes- lab findings

Answer 4

• macro-ovalocytes
• Pelger-Huet- neutrophils- bilobed nucleus
• bone marrow- hypercellular
• erythroid hyperplasia
• abnormal erythropoiesis- megaloblastic, nuclear budding, multinucleated erythroid precursors
• ringed sideroblasts- prussian blue stain
• deletions of chrom 5 and 7

Question 5

Myelodysplastic syndromes- tx

Answer 5

• anemia and low erythropoietin- epoetin
• thrombopoietin analogs
• immunosuppressive therapy- ATG

Question 6

5q- syndrome- tx

Answer 6

-lenalidomide

used for transfusion-dep anemia due to myelodysplasia

Question 7

high-risk myelodysplasia- tx

Answer 7

-azacitidine

Question 8

Myelodysplastic syndromes- prognosis

Answer 8

• allogeneic transplantation- only curative therapy- 30-60% cure rate
• die of infections or bleeding
• 5q- syndrome- favorable prognosis- 5 yr survival 90%
• excess blasts or CMML- high risk (50%) of developing acute leukemia, and short survival (<2 yrs) w/o allogeneic transplantation

Question 9

Myelodysplastic syndromes- international prognostoic scoring system

Answer 9

-based on % of bone marrow blasts, cytogenetics, and severity of cytopenias

Question 10

Myeloproliferative disorders- 4 disorders

Answer 10

• CML (chronic myelocytic leukemia)
• PV (polycythemia vera)
• ET (essential thrombocythemia)
• MF (myelofibrosis)

Question 11

Polycythemia vera- essentials of dx

Answer 11

• JAK2 mutation
• inc RBC mass
• splenomegaly
• normal arterial oxygen saturation
• usually elevated WBC and plt count

Question 12

Polycythemia vera- signs, sx’s

Answer 12

• inc blood viscosity- HA, dizziness, blurred vision, fatigue
• median age 60 yo
• engorged retinal v’s
• splenomegaly
• thrombosis- most common complication

Question 13

Polycythemia vera- lab

Answer 13

• hematocrit > 54% in males, 51% in females
• low erythropoietin levels
• dx confirmed with JAK2 mutation screening

Question 14

secondary causes of polycythemia

Answer 14

• hypoxia
• smoking
• kidney lesions
• erythropoieitn-secretin tumors (rare)

Question 15

Polycythemia vera- tx

Answer 15

• phlebotomy- 1 unit of blood removed weekly until hematocrit is < 45%- produces iron def (wanted!)
• myelosuppressive therapy may be indicated if high phlebotomy requirement, thrombocytosis, and pruritus- hydroxyurea!
• low dose aspirin- reduce thrombosis risk

Question 16

Polycythemia vera- prognosis

Answer 16

• indolent- survival 15 yrs

- can convert to myelofibrosis or CML

Question 17

Essential Thrombocytosis- essentials of dx

Answer 17

• elevated plt count in absence of other causes
• normal RBC mass
• absence of BCR/ABL gene

Question 18

Essential Thrombocytosis- signs, sx’s

Answer 18

• age 50-60
• risk of thrombosis
• erythromelalgia- relieved by aspirin

Question 19

Essential Thrombocytosis- lab

Answer 19

• elevated plt count- may be over 2,000,000
• large platelets- peripheral BS
• inc numbers of megakaryocytes in BM

Question 20

Essential Thrombocytosis- vs reactive thrombocytosis

Answer 20

• reactive- plt count rarely is > 1,000,000
• JAK2 mutations- 50%
• lack of erythrocytosis- vs PV!
• no BCR/ABL gene mutation- vs CML!

Question 21

Essential Thrombocytosis- tx

Answer 21

• hydroxyurea

- if not tolerated b/c of anemia- anagrelide

Question 22

Essential Thrombocytosis- prognosis

Answer 22

• indolent- survival 15 yrs
• source of morbidity- thrombosis
• BM can become fibrotic- 10% of myelofibrosis progression after 15 yrs

Question 23

Primary Myelofibrosis- essentials of dx

Answer 23

• striking splenomegaly
• teardrop poikilocytosis on PS
• leukoerythroblastic blood picture; giant abnormal plts
• initially hypercellular, then hypocellular BM with reticulin or collagen fibrosis

Question 24

Primary Myelofibrosis- sx and signs

Answer 24

• > 50 yo
• fatigue (anemia) or abd fullness (splenomegaly)
• progressive BM failure- thrombocytopenia (bleeding), splenic infarction (enlarged spleen)

Question 25

Primary Myelofibrosis- lab

Answer 25

• anemic
• PBS- TRIAD- poikilocytosis, leukoerythroblastic blood, giant degranulated plt forms
• teardrop forms in red cell line
• BM- dry tap
• silver stain- inc reticulin fibers
• JAK2 and MPL mutations

Question 26

Primary Myelofibrosis- tx

Answer 26

-if splenomegaly- hydroxyurea

Question 27

CML- essentials of dx

Answer 27

• elevated WBC
• left-shifted myeloid series but with a low % of promyelocytes and blasts
• BCR/ABL gene

Question 28

CML- sx and signs

Answer 28

• 55 yo
• fatigue, night sweats, low-grade fevers
• splenomegaly

Question 29

CML- lab

Answer 29

• elevated WBC- usually 150,000
• peripheral blood- left shifted myeloid series
• BCR/ABL Gene
• can progress to accelerated and blast phases- anemia and thrombocytopenia- blast phase is when blasts > 20% BM cells

Question 30

reactive leukocytosis vs CML

Answer 30

-reactive- WBC < 50,000, no splenomegaly, no BCR/aBL gene