Myelodysplastic syndrome

Question 1

Lab profile (features of anemia and other thrombocytopenias)

Answer 1

• Anemia: low retic count + commonly macrocytic
• leukopenia (50%)
• varying degrees of thrombocytopenia (25%)
• dysplastic cells on smear (≥10 percent of erythroid precursors, granulocytes, or megakaryocytes)
• inappropriately low retic count
• blasts <20%
• commonly monocytosis

Question 2

Indications for treatment of lower risk MDS

Answer 2

1) Requiring frequent transfusions

Question 3

Initial therapy for intermediate-2/high-risk MDS

Answer 3

IF non candidate for HSCT → azacitidine or until disease progression or intolerable side effects
IF candidate → AlloHSCT

Question 4

pathophysiology of MDS

Answer 4

MDS is thought to arise from mutations in the *multipotent stem cell, but the specific defects responsible for these diseases remain poorly understood. Differentiation of blood precursor cells is impaired, (this leads to multiple cytopenias) and a *increase in apoptotic cell death occurs in bone marrow cells.

Question 5

venetoclax mechanism

Answer 5

Blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells.

Question 6

Management of patient with clinically significant anemia

Answer 6

1) measure epo. if below 500, give epo.

Question 7

What are the hypomethylating agents?

Answer 7

azacetadine or decitabine

Question 8

Risk stratification score used for MDS

Answer 8

Revised International Prognostic Scoring System (IPSS-R)

Question 9

General diagnosis of MDS

Answer 9

1) Cytopenias
2) Low blast percentage in marrow
3) Morphologic evidence of dysplasia

Question 10

Workup of suspected MDS

Answer 10

• **peripheral smear

- bone marrow aspirate and biopsy

Question 11

MDS-SLD means

Answer 11

MDS-single lineage dysplasia (1 or 2 cytopenias, but other cell lines are normal)

Question 12

What are the dysplastic cells you may see on peripheral smear indicating MDS?

Answer 12

≥10 percent of erythroid precursors, granulocytes, or megakaryocytes

Question 13

Diagnostic criteria

Answer 13

1) cytopenia in at least one blood lineage (but can have single lineage dysplasia MDS)
2) dysplasia in 10% or more of nucleated cells in at least one lineage
3) less than 20% blasts in blood and bone marrow
4) and/or characteristic cytogenetic findings

Question 14

what does CHIP stand for?

Answer 14

• clonal hematopoiesis of indeterminate potential

Question 15

what does risk stratification depend on?

Answer 15

• percentage of bone marrow blasts
• number and severity of cytopenias
• cytogenetic findings

Question 16

Examples of lower-intensity treatments

Answer 16

• epoetin alfa
• thrombopoietin receptor agonists
• neupogen
• luspatercept
• hypomethylating agents (HMA; eg, azacitidine, decitabine)
• immunosuppressive therapy, lenalidomide
• targeted agents (eg, IDH inhibitors).

Question 17

Actionable mutation in MDS

Answer 17

IDH1 or IDH2

Question 18

Adverse genetic features in MDS

Answer 18

1) TP53 mutation

2) adverse cytogenetic abnormalities

Question 19

Management of high risk MDS patient

Answer 19

IF adverse genetic features present, HSCT is preferable
IF not, then targeted therapy with IDH1 agent is preferable
IF no IDH1, then transplant

Question 20

what are the IDH inhibitor drugs?

Answer 20

enasidenib and ivosidenib

Question 21

procrit generic name

Answer 21

EPO

Question 22

Marrow in MDS

Answer 22

• typically hypercellular but can be hypocellular (hypocellular MDS)

Question 23

how to determine expected cellularity of marrow in a patient

Answer 23

cellularity = 100 - age

Question 24

Most favorable mutation

Answer 24

SF3B1

Question 25

FDA approved drug for MDS w/ ring sideroblasts

Answer 25

luspatercept

Question 26

Combination therapy approved for MDS

Answer 26

decitabine and cedazuridine (inqovi)

Question 27

WHO categories for MDS

Answer 27

``` MDS with single lineage dysplasia MDS with multilineage dysplasia MDS with ring sideroblasts MDS with excess blasts MDS with isolated del(5q) ```

Question 28

NCCN preferred/category 1 HMA for higher risk

Answer 28

azacitadine

Question 29

Role for IDH inhibitors

Answer 29

Ongoing research, second line (confirm, not sure)

Question 30

Dysplastic features on smear or marrow aspirate suggesting MDS

Answer 30

Ovalomacrocytosis is the most common morphologic abnormality, dysplastic PMNs, elliptocytes, teardrops, stomatocytes, or acanthocytes (spur cells), basophilic stippling, Howell-Jolly bodies, hypolobulated megakaryocytes megaloblastoid nucleated red cells

Question 31

When is lenalidomide used in MDS

Answer 31

5q deletion, low and intermediate risk MDS, with anemia

Question 32

what are the IPSS-R risk categories?

Answer 32

- low - intermediate-1 - intermediate-2 - high - very high

Question 33

Staging system for MDS

Answer 33

IPSS-R

Question 34

Number of blasts required for MDS with excess blasts-1

Answer 34

5-9%

Question 35

Number of blasts required for MDS with excess blasts-2

Answer 35

10-19%

Question 36

Auer rods in MDS?

Answer 36

You can have auer rods in MDS-EB2 | *Not all auer rods are APML

Question 37

frequency of chromosomal translocations in MDS vs. AML

Answer 37

less common in MDS

Question 38

Management of patient with characteristics AML cytogenetic abnormalities (8;21, 15;17, inversion 16)

Answer 38

3+7 chemotherapy

Question 39

Indication for lenalidomide

Answer 39

Transfusion-dependent patients with low or intermediate-1 MDS + 5q deletion

Question 40

duration of azacitadine in MDS

Answer 40

Continue until progression or unacceptable toxicity (data shows interruption of HMAs is associated with earlier relapse and poor prognosis)

Question 41

why azacitidine vs. decitabine

Answer 41

- haven't been compared head to head | - only aza has demonstrated a survival benefit, so it is in guidelines

Question 42

azacitidine and decitabine formulation

Answer 42

- aza = can also be PO or IM | - decitabine is IV

Question 43

Variables included in IPSS-R

Answer 43

1) cytogenetics 2) blasts 3) hgb 4) plt 5) ANC

Question 44

trade name for azacitadine

Answer 44

vidaza

Question 45

what is inqovi

Answer 45

Oral combination of decitabine + cedazuridine

Question 46

Preferred HMA for non-transplant candidates

Answer 46

azacitidine

Question 47

generic name for aranesp

Answer 47

darbopoeitin

Question 48

Treatment durations for HMAs with MDS

Answer 48

- Until progression or unacceptable toxicity (data shows that interruption of HMAs in a patient who is responding is associated with an earlier relapse and a poor prognosis)

Question 49

Can MDS be cured?

Answer 49

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for MDS

Question 50

Worst mutation to have in MDS

Answer 50

TP53

Question 51

What is CCUS?

Answer 51

clonal mutation + cytopenia BUT doesn't meet WHO criteria for a heme neoplasm

Question 52

Target hgb range in MDS

Answer 52

10

Question 53

Very good cytogenetic findings in MDS

Answer 53

Deletion Y, del 11