Chapter 14: Myelodysplasia

Question 1

What are myelodysplastic syndromes?

Answer 1

A group of disorders associated with multipotent stem cells that causes bone marrow failure.

Question 2

What are the characteristic features of Myelodysplasia?

Answer 2

Ineffective hemopoiesis and cytopenia with marrow of normal or increased cellularity.

Question 3

What is the pathogenesis of myelodysplasia?

Answer 3

Damage to hematopoietic progenitors causes increased stem cell proliferation with decreased differentiation. The result is cytopenia with hypercellular bone marrow.

Question 4

What is the epidemiology of MDS?

Answer 4

(1) the incidence is 4 in 100,000
(2) More common in men
(3) over 50% of patients are over 70.

Question 5

What are the clinical features of MDS?

Answer 5

(1) anemia
(2) thrombocytopenia
(3) neutropenia.

Question 6

MDS can occur as a secondary feature of what conditions?

Answer 6

(1) excess alcohol intake
(2) Magaloblastic anemia
(3) chemotherapy
(4) growth factor therapy

Question 7

What hematologic findings are associated with MDS?

Answer 7

(1) pancytopenia
(2) Macrocytic, dimorphic, hypochromic, or normocytic anemia may be seen.
(3) Low reticulocyte count.
(4) Impaired abnormal granulocytes
(5) Pelger anomaly

Question 8

What are the characteristics of the bone marrow in MDS?

Answer 8

(1) abnormal celllularity (hypocellular 20%
(2) Ring sideroblasts
(3) Abnormal morphology and development of multiple cell lines.

Question 9

What proportion of the bone marrow must be dysplastic for a diagnosis of MDS to be made?

Answer 9

10% or more.

Question 10

What genetic abnormalities are associated with MDS?

Answer 10

(1) Monosomy 5 or 7
(2) Trisomy 8
(3) partial deletion of 5q
(5) RAS mutation in 20% of cases
(6) FMS mutation in 15% of cases

Question 11

What factors are used to classify myelodysplastic syndromes?

Answer 11

Blood count
Morphological appearance
number of blast cells in the bone marrow or blood.

Question 12

What is refractory anemia?

Answer 12

MDS that only effects the red cell lineage.

Question 13

What is refractory anemia with multilineage dysplasia?

Answer 13

MDS that effects multiple cell lines.

Question 14

What is unclassified MDS?

Answer 14

MDS that effects only one non-red cell lineage.

Question 15

Why is treating MDS extremely difficult?

Answer 15

Many chemotherapies make the MDS worse.

Question 16

What is low grade MDS?

Answer 16

(1) less than 5% blasts in the bone marrow
(2) Only one cytopenia
(3) favorable cytogenetics

Question 17

How is low grade MDS treated?

Answer 17

(1) supportive therapy(blood transfusions)
(2) EPO, G-CSF
(3) Immunosuppression (ATG, ciclosporin)

Question 18

When is supportive therapy alone used for high-risk MDS?

Answer 18

In elderly patients with other health problems high risk MDS may be treated only with blood/platelet transfusions, and or antimicrobial therapies.

Question 19

For what form of MDS is single agent chemotherapy sometimes helpful?

Answer 19

Refractory anemia with excess blasts (RAEB) is sometimes treated with single agent chemotherapy. (Hydroxyurea, etoposide, 6-MP, C-ARA, azacytidine, or decitabine)

Question 20

When is intensive chemotherapy used to treat MDS?

Answer 20

High risk MDS may be treated with intensive chemotherapy however despite high remission rates relapse is almost inevitable.

Question 21

How can MDS be cured?

Answer 21

By stem cell transplant.

Question 22

What are the criteria for high risk MDS?

Answer 22

(1) greater than 5% blasts
(2) unfavorable cytogenetics
(3) Pancytopenia

Question 23

What are myelodysplastic/myeloproliferative disorders?

Answer 23

disorders characterized by dysplastic cells and increased numbers of circulating cells.

Question 24

What is chronic myelomonocytic leukemia (CMML)?

Answer 24

MDS characterized by persistent monocytosis and leukocytosis.

Question 25

What are the presenting features of CMML?

Answer 25

(1) skin rashes
(2) gum hypertrophy
(3) lymphadenopathy
(4) splenomegaly (50%)

Question 26

How is CMML treated?

Answer 26

Hydroxyurea, etoposide, mercaptopurine standard patients and
Stem cell transplant in younger patients.

Question 27

What is the prognosis for CMML?

Answer 27

median survival is two years.