Myelodysplastic Syndromes

Question 1

What are the three classifications of MDS with defining genetic abnormalities?

Answer 1

MDS with low blasts and isolated 5q deletion
MDS with low blasts and SF3B1 mutation
MDS with biallelic TP53 inactivation

Question 2

What are the four categories of morphologically defined MDS?

Answer 2

MDS with low blasts
MDS, hypopalstic
MDS, with increased blasts
MDS with fibrosis

Question 3

What is the criteria for definition of MDS with low blasts?

Answer 3

PB <2%
BM <5%

Question 4

Which WHO MDS classifications (3) are considered high risk?

Answer 4

Biallelic TP53
MDS-Increased blasts
MDS with fibrosis

Question 5

What cytogenetic abnormalities place a patient with MDS into very good prognostic group? (2)

Answer 5

del11q
-Y

Question 6

What cytogenetic abnormalities place a patient with MDS into good risk? (3)

Answer 6

normal
del5q
del12p
del20q

Question 7

What cytogenetic abnormalities place a patient with MDS into intermediate risk? (4)

Answer 7

del7q
+8
i(17q)
+19

Question 8

What cytogenetic abnormalities place a patient with MDS into poor risk? (2)

Answer 8

inv(3)
-7

Question 9

What cytogenetic abnormalities place a patient with MDS into very poor risk?

Answer 9

> 3 abnormalities

Question 10

What is the prognostic tool used in MDS? What cutoff is used for high/low risk?

Answer 10

IPSS-R
<3.5 is low risk, >3.5 is high risk

Question 11

You have patient with low risk MDS with isolated symptomatic anemia. What are the two preferred treatment options?

Answer 11

ESAs
Luspatercept (with RS or SF3B1 mut)

Question 12

Luspatercept mechanism of action

Answer 12

SMAD2/3

Question 13

What is the indication for luspatercept?

Answer 13

Low risk MDS with ringed sideroblasts or SF3B1 mutation

Question 14

What is the treatment of choice for MDS-5q-?

Answer 14

Lenalidomide

Question 15

You have a patient with low-risk MDS with no cytogenetic abnormalities and isolated anemia. You treat with darbepoietin but she stops responding and Hgb drops again. Repeat marrow shows no change. Next treatment?

Answer 15

Lenalidomide (off label)

Question 16

Best treatment for low-risk MDS with isolated thrombocytopenia?

Answer 16

Thrombopoietin agonists

Question 17

Patient with low-risk MDS and isolated thrombocytopenia, no longer responds to TPO agonists. What is preferred treatment?

Answer 17

Hypomethylating agent

Question 18

You have a patient with low-risk MDS with isolated thrombocytopenia. Who should you be very cautious in giving a TPO agonist to?

Answer 18

Excess blasts

Question 19

Preferred treatment options (2) for low risk MDS with multilineage dysplasia?

Answer 19

HMAs (Decitabine or Azacitidine)
ATG (best for hypoplastic MDS)

Question 20

Preferred treatment for high-risk MDS who are not HCT candidate? (2)

Answer 20

Azacitidine (Decitabine didn’t have any OS benefit)
Cedazuridine/Decitabine

Question 21

Preferred treatment for high-risk MDS?

Answer 21

HCT, if they are a candidate

Question 22

How do you diagnose MDS?

Answer 22

At least one cytopenia
Dysplasia >10% in at least one lineage
Marrow usually hypercellular

Question 23

Clinical characteristics of MDS/MPN with neutrophilia?

Answer 23

Marrow dysplasia
Leukocytosis with left shift
<20% blasts
N BCR/ABL or PDGFRA rearrangements
No monocytosis

Question 24

What mutations are associated with MDS/MPN with neutrophilia?

Answer 24

SETBP1, ASXL1, RAS, CSF3R

Question 25

How do CSF3R mutations affect the management of MDS/MPN with neutrophilia?

Answer 25

Proximal mutation (T615A, T618I): responds to ruxolitinib
Distal mutations: respond to dasatinib

Question 26

What mutation is commonly seen in MDS with ringed sideroblasts?

Answer 26

SF3B1

Question 27

What are the 5 components of IPSS-R?

Answer 27

Cytogenetics, bone marrow blasts, hemoglobin, platelets, ANC

Question 28

What are the most commonly mutated (3) genes in CHIP?

Answer 28

DNMT3a
TET2
ASXL1

Question 29

What is the difference between ICUS and CCUS?

Answer 29

CCUS has a clonal mutation in myeloid related genes. Neither have diagnostic criteria for MDS, or any malignancy.

Question 30

Treatment for CHIP?

Answer 30

Observation

Question 31

In someone with therapy-related MDS from previous anthracycline or etoposide chemotherapy, what is the characteristic chromosomal abnormality?

Answer 31

11q23

Question 32

Typical latency of therapy related MDS from RT or alkylating agents?

Answer 32

5-10 years

Question 33

What is a way to predict a patients response to ESAs?

Answer 33

Low EPO has a higher likelihood of response

Question 34

What is the appropriate time for transplant in MDS?

Answer 34

High risk: immediately
Low risk: at progression (after ESAs, Luspatercept, len, etc.)

Question 35

Treatment of a patient with CMML and PDGFRB mutation?

Answer 35

Imatinib

Question 36

In therapy-related MDS from previous treatment with alkylating agents, what are the commonly seen chromosomal abnormalities?

Answer 36

Monosomy 5 or 7

Question 37

What is the WHO definition of MDS-IB1?

Answer 37

in BM:
5-9% blasts
no Auer rods

Question 38

What is the WHO definition for MDS-IB2?

Answer 38

In BM:
10-19% blasts
Auer rods

Question 39

Preferred treatment for high risk MDS with 5q deletion?

Answer 39

Still transplant or azacitadine
Len is only for low risk

Question 40

For how long do you treat a high risk MDS patient with an HMA?

Answer 40

until failure or toxicity.
Even with a good response, stopping HMA is associated with earlier relapse and poorer prognosis