MDS and Myeloproliferative CIS

Question 1

Myelodysplastic Syndromes- clinical picture

Answer 1

• pancytopenia with hyperplastic marrow
• risk for development of acute leukemia
• 6-7 decade
• 1/2 are asymptomatic

Question 2

Myelodysplastic Syndromes- etiology

Answer 2

• chemotherapy- breast cancer, HL and NHL, acute leukemia- Alkylating agents, anthracycline abx
• radiation
• petrochemical exposure

Question 3

Myelodysplastic Syndromes- cytogenetics

Answer 3

• loss of long arm of chrom 5 or 7
• inversion 16
• trisomy 8

Question 4

Myelodysplastic Syndromes

Answer 4

• refractory anemia
• refractory anemia with ringed sideroblasts
• refractory anemia with excess blasts
• AML with multilineage dysplasia following a myelodysplastic syndrome
• CMML

Question 5

in pts with pancytopenia- potential dx

Answer 5

• hypersplenism
• aplastic anemia
• myelodysplasia

Question 6

Refractory anemia with Ringed Sideroblasts (RARS)

Answer 6

• ringed sideroblasts in marrow precursors

- lowest risk of conversion to AML

Question 7

Refractory anemia with Ringed Sideroblasts (RARS)- rule out what?

Answer 7

Pyridoxine (B6) def!!!- also have ringed sideroblasts

• check B6 level on every pt with ringed sideroblasts
• replace B6 for 6 months- if no improvement- pt has RARS!!

Question 8

Myelodysplasias- adverse prognostic features

Answer 8

poor prognosis- median survival 2 yrs

• marrow blasts > 5%
• plts < 100,000
• hemoglobin < 10
• neutrophils < 2500
• age > 60 yo

Question 9

Myelodysplasias- poor prognosis- cytogenetics

Answer 9

• monosomy 7
• hypodiploidy
• mult abnormalities

Question 10

Myelodysplasias- favorable prognosis- cytogenetics

Answer 10

-5q- syndrome- responds to lenalidomide!!!

Question 11

Myelodysplasias- tx

Answer 11

supportive care

• avoid meds that damage marrow
• aggressive tx of infections
• transfuse PRBCs when sx (anemic)
• transfuse plts for bleeding or in prep for surgery
• watch for iron overload- desferrioxamine

Question 12

Myelodysplasias- tx- other supportive care

Answer 12

• EPO- expensive

- androgens variably effective

Question 13

Myelodysplasias- low/intermediate intensity therapy

Answer 13

• Hypomethylating agents- azacitidine, decitabine- cytotoxicity on abnormal BM hematopoietic cells
• Lenalidomide- for 5q- syndrome ONLY!

Question 14

Myelodysplasias- high intensity therapy

Answer 14

AML induction-style tx!!
-response rate- 54% with 15% mortality rate at 30 days
-survival- 13-15 months
HSC transplantation- in pts < 60 with an HLA-matched sibling donor!!

Question 15

Myelofibrosis- what is it? triad?

Answer 15

• myeloproliferative disorder
• marrow fibrosis and extramedullary hematopoiesis
• triad- leukoerythroblastic anemia, poikilocytosis, splenomegaly

Question 16

Myelofibrosis- pathogenesis

Answer 16

• inc reticulin deposition in marrow (by marrow fibroblasts)
• inc PDGF
• dry tap
• JAK2 mutations- 50%

Question 17

Myelofibrosis- dz course; tx

Answer 17

• chronic in nature, but progressive
• asx for many yrs
• pancytopenia and organomegaly- later stages
• tx- observation if asx
• some pts treated with BMT; no tx available to reverse fibrosis

Question 18

Myelofibrosis- tx for pancytopenia

Answer 18

• transfusion for anemia
• EPO (if < 500)
• transfuse plts if bleeding
• GFs for neutropenia
• tx infections aggressively
• infection most common cause of death!

Question 19

Myelofibrosis- tx for splenomegaly

Answer 19

• hydroxyurea
• radiation
• splenectomy- can be dangerous

Question 20

Myelofibrosis- tx- new JAK inhibitor

Answer 20

-Ruxolitinib

Question 21

Myelofibrosis- curative tx?

Answer 21

allogeneic stem cell transplantation