NCCN MDS

Question 1

This disease is suspected in the presence of peripheral blood dysplasia, blasts, or associated cytogenetic abnormalities.

Answer 1

MDS

Question 2

Defined as values lower than standard lab hematologic levels, being cognizant of age, sex, ethnic, and altitude norms

Answer 2

Cytopenias

Question 3

What test should be performed if standard cytogenetics (with ≥20 metaphases) cannot be obtained?

Answer 3

A chromosome microarray analysis (CMA; also known as chromosome genomic array testing [CGAT]) or MDS-related fluorescence in situ hybridization (FISH) panel should be performed.

-If karyotype is normal, then consider CMA. Note that CMA will detect not
only somatic but also constitutional (germline) changes.

Question 4

A more representative measure of folate stores and is the preferred test to serum folate

Answer 4

RBC folate

Question 5

An accurate way to assess B12 status and is mandatory to the vitamin B12 evaluation, particularly for patients with possible pernicious anemia.

Answer 5

Serum methylmalonic acid testing

Question 6

Identify mutated gene:
Associated with normal karyotypes. More frequent in CMML (40%–60%).
Common in CHIP and CCUS.

Answer 6

TET2

Question 7

Identify mutated gene:
More frequent occurrence in AML, particularly R882 mutations.
Common in CHIP and CCUS.

Answer 7

DNMT3A

Question 8

Identify mutated gene:
Independently associated with a poor prognosis in MDS and CMML. More frequent in CMML (40%–50%). Common in CHIP and CCUS.

Answer 8

ASXL1

Question 9

Identify mutated gene:
Independently associated with a poor prognosis in MDS and MDS/MPN. More frequent in CMML (12%).

Answer 9

EZH2

Question 10

Identify mutated gene:
Strongly associated with RS and more frequent in MDS-RS (80%). Independently associated with a more
favorable prognosis.

Answer 10

SF3B1

Question 11

Identify mutated gene:
More frequent in CMML (40%) and associated with a poor prognosis.

Answer 11

SRSF2

Question 12

Identify mutated gene:
Independently associated with a poor prognosis. More frequent with complex karyotypes (50%) and
del(5q) (15%–20%). May predict resistance or relapse to lenalidomide.

Answer 12

TP53

Question 13

Identify mutated gene:
Associated with a poor prognosis, particularly in patients predicted to have lower-risk MDS. More
frequent in CMML and JMML (~15%).

Answer 13

NRAS

Question 14

Identify disorder:

Hema findings/myeloid malignancy: Increased myeloid malignancies
and T-cell ALL in people aged
7–29 years

Clinical features include:
sensitivity to ultraviolet light, experiencing severe sunburns within minutes of exposure, dry skin (xeroderma), freckling (pigmentosum), hearing loss, poor coordination, loss of intellectual function, seizures, and development of squamous cell carcinomas and melanomas often as early as 10 years old in sun-exposed areas.

Answer 14

Xeroderma pigmentosum C (XPC)

Question 15

Give AML-defining genetic abnormalities

Answer 15

Question 16

How many units of PRBC transfusions to consider daily iron chelation?

Answer 16

If >20 to 30 RBC transfusions have been received, consider daily chelation with deferoxamine SC or deferasirox orally to decrease iron overload, particularly for patients who have lower-risk MDS or who are potential transplant candidates (LOW/INT-1).

Question 17

Target ferritin level for patients with serum ferritin levels >2500 ng/mL

Answer 17

For patients with serum ferritin levels >2500 ng/mL, aim to decrease ferritin
levels to <1000 ng/mL.

Question 18

Parameters used in REVISED INTERNATIONAL PROGNOSTIC SCORING SYSTEM (IPSS-R)

Answer 18

Cytogenetic, marrow blasts, hemoglobin, platelets, ANC

Question 19

Cytogenetic risks based on IPSS-R:

Answer 19

Cytogenetic risks:
Very good = -Y, del(11q);
Good = normal, del(5q), del(12p),
del(20q), double including del(5q);
Intermediate = del(7q), +8, +19, i(17q), any other single or double independent clones;
Poor = -7, inv(3)/t(3q)/del(3q), double including -7/del(7q), complex: 3 abnormalities;
Very poor = complex: >3 abnormalities.

Question 20

Parameters used in WHO-BASED PROGNOSTIC SCORING SYSTEM (WPSS)

Answer 20

WHO category: RCUD, RARS, MDS
with isolated del(5q); RCMD, RAEB-1, RAEB-2
Karyotype: Good, intermediate, poor
Severe anemia (hemoglobin <9 g/dL
in males or <8 g/dL in females)

Question 21

Identify mutated gene:
Occurs in LGL associated with MDS; associated with immune bone marrow failure.

Answer 21

STAT3

Question 22

Identify mutated gene:
Associated with therapy-related MDS, but not associated with adverse prognosis independent of TP53.
Common in CHIP and CCUS.

Answer 22

PPM1D

Question 23

Identify mutated gene:
VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) associated with systemic
autoinflammatory and hematologic diseases, mainly MDS.

Answer 23

UBA1

Question 24

Patients with karyotypes ____, _____, or _____ are considered to have AML even if the marrow blast count is less than 20%.

Answer 24

karyotypes t(8;21), t(15;17), or inv(16)

Question 25

This is most useful in detecting aberrant immature myeloid lineages often observed in MDS.

Answer 25

Flow Cytometry (FCM)

Question 26

For patients with lower-risk disease MDS-5q (low blasts) del(5q) ± one
other cytogenetic abnormality
IPSS Low/Intermediate-1 and Serum EPO ≤500 mU/mL. What is the preferred treatment? Specify recommended dose.

Answer 26

Preferred: Lenalidomide
Recommended Lenalidomide initial dose is: 10 mg/day for 21 out of 28 days or 28 days monthly for 2–4 months to assess response. Use caution for patients with low platelet and neutrophil counts; consider modifying lenalidomide dose. Lenalidomide 10 mg daily if absolute neutrophil count >0.5, platelets >50,000

Question 27

Patient with lower-risk disease MDS-5q (low blasts) del(5q) ± one
other cytogenetic abnormality
IPSS Low/Intermediate-1 and Serum EPO ≤500 mU/mL, but cannot afford Lenalidomide. What are the other recommended treatments? Specify dose.

Answer 27

Other recommended treatments:
Erythropoiesis-stimulating
agent (ESA) (epoetin alfa or
darbepoetin alfa)

Dosing is 40,000–60,000 U 1–2 times per week subcutaneously (SC) for epoetin alfa and 150–300 mcg every other week SC for darbepoetin alfa. For lack of response, escalate the dose. At some institutions, darbepoetin alfa has been administered using doses up to 500 mcg every other week. An FDA-approved biosimilar is an appropriate substitute for epoetin alfa.

Question 28

Patient with lower-risk disease MDS-5q (low blasts) del(5q) ± one
other cytogenetic abnormality
IPSS Low/Intermediate-1 and Serum EPO ≤500 mU/mL but no response to Lenalidomide or ESA. Noted serum EPO >500 mU/mL and with good probability to respond to IST. What is the management?

Answer 28

No response to Lenalidomide means Lack of ≥1.5 gm/dL rise in hemoglobin or lack of a decrease in RBC transfusion requirement by 3 to 6 months of treatment.

No response to ESA means Lack of ≥1.5 gm/dL rise in hemoglobin or lack of a decrease in RBC transfusion requirement by 6 to 8 weeks of treatment.

Check serum EPO.
For symptomatic anemia with serum EPO >500 mU/mL and with good probability to respond to IST (Patients generally ≤60 years and with ≤5% marrow blasts, or those with hypocellular marrows, PNH clone positivity, or STAT3-mutant cytotoxic T-cell clones), give ATG + cyclosporin A ± eltrombopag.

Question 29

For patients with lower-risk disease with MDS-SF3B1 (low blasts) no del(5q) ± other cytogenetic abnormalities with RS ≥15% (or RS
≥5% with an SF3B1 mutation). With symptomatic anemia. What is the category 1 treatment? Specify recommended dose.

Answer 29

Luspatercept-aamt
The starting dose of luspatercept-aamt is 1 mg/kg every 3 weeks, which may be increased to 1.33 mg/kg every 3 weeks if not RBC transfusion-free after at least two consecutive doses (6 weeks) at the 1 mg/kg starting dose. The dose may be further increased to 1.75 mg/kg every 3 weeks if not RBC transfusion-free after at least 2 consecutive doses (6 weeks) at the 1.33 mg/kg dose.

Question 30

Patient with lower-risk disease with MDS-SF3B1 (low blasts) no del(5q) ± other cytogenetic abnormalities with RS ≥15% (or RS ≥5% with an SF3B1 mutation). With symptomatic anemia. On Luspatercept but no response after 3-6 months of treatment. What is the next step of management? Specify recommended doses.

Answer 30

Check serum EPO.
If Serum EPO ≤500 mU/mL, give Epoeitn alfa ± G-CSF or
Darbepoetin alfa ± G-CSF

Dosing is 40,000–60,000 U 1–2 times per week subcutaneously (SC) for epoetin alfa and 150–300 mcg every other week SC for darbepoetin alfa.
Dosing is 1–2 mcg/kg 1–2 times per week SC for G-CSF.

If Serum EPO >500 mU/mL, consider
Lenalidomide.
Recommended Lenalidomide initial dose is: 10 mg/day for 21 out of 28 days or 28 days monthly for 2–4 months to assess response. Use caution for patients with low platelet and neutrophil counts; consider modifying lenalidomide dose. Lenalidomide 10 mg daily if absolute neutrophil count >0.5, platelets >50,000