Myelodysplastic Syndromes

Question 1

What are risk factors for MDS?

Answer 1

• incidence of MDS increases with age - previous chemotherapy causing DNA damage (alkylating agents, topoisomerase II inhibitors) or radiation - inherited defects in DNA repair (Fanconi anemia) - Down syndrome

Question 2

What are signs/symptoms of MDS?

Answer 2

• Fatigue, easy bleeding, infections due to neutropenia - Normocytic or macrocytic anemia - Nucleated erythrocytes and hypolobulated, hypogranular neutrophils on peripheral smear - +/- affected platelet and neutrophil counts (however not functional) - hypercellular bone marrow, dysplasia in affected lineages

Question 3

What is this?

Answer 3

Hypo-lobulated, hypogranular neutrophil consistent with MDS

Question 4

What is the differential diagnosis for cytopenias and dysplastic changes?

Answer 4

• B12/folate deficiencies
• medication effects (mycophenolate mofetil)
• recent cytotoxic chemotherapy or radiation therapy
• HIV infection
• MDS

Question 5

What is the differential diagnosis for sideroblastic anemia?

Answer 5

• congenital sideroblastic anemias
• drug toxicity (chloramphenicol, isoniazid)
• Alcoholism
• Copper deficiency
• Zinc excess
• MDS

Question 6

Treatment of asymptomatic pts with MDS:

Answer 6

• can be observed closely
• blood counts checked periodically
• bleeding related to thrombocytopenia -> transfusions

Question 7

What is the concern with multiple transfusions in MDS pts?

Answer 7

• iron overload syndromes
• iron chelation therapy may be considered if ferritin >1000

Question 8

• Treatment of pts with symptomatic anemia and lower-risk MDS:

Answer 8

• erythrocyte stimulating agents (epo, darbepoietin) -> may improve Hgb levels
• +/- G-CSF; no evidence of progression to AML

Question 9

Treatment of higher-risk MDS:

Answer 9

• Azacitadine, Demcitabine
• better complete response rates, improved median survival
• decreased risk of transformation to AML

Question 10

Treatment of transfusion dependence in lower-risk MDS pts:

Answer 10

• lenalidomide leads to transfusion independence

Question 11

What are signs/symptoms of CMML?

Answer 11

• chronic myelomonocytic leukemia: features of MDS and myeloproliferative disorder
• weight loss, sweats, HSM
• leukocytosis with absolute monocyte count >1000/mcL is required for diagnosis
• may also have anemia, thrombocytopenia

Question 12

What is treatment of CMML?

Answer 12

• supportive treatment
• hydroxyurea can palliate symptoms and HSM
• younger pts can undergo allogeneic HSCT = curative
• only limited experience with azacitadine, demcitabine