Myelodysplastic Syndromes Flashcards
What are the three classifications of MDS with defining genetic abnormalities?
MDS with low blasts and isolated 5q deletion
MDS with low blasts and SF3B1 mutation
MDS with biallelic TP53 inactivation
What are the four categories of morphologically defined MDS?
MDS with low blasts
MDS, hypopalstic
MDS, with increased blasts
MDS with fibrosis
What is the criteria for definition of MDS with low blasts?
PB <2%
BM <5%
Which WHO MDS classifications (3) are considered high risk?
Biallelic TP53
MDS-Increased blasts
MDS with fibrosis
What cytogenetic abnormalities place a patient with MDS into very good prognostic group? (2)
del11q
-Y
What cytogenetic abnormalities place a patient with MDS into good risk? (3)
normal
del5q
del12p
del20q
What cytogenetic abnormalities place a patient with MDS into intermediate risk? (4)
del7q
+8
i(17q)
+19
What cytogenetic abnormalities place a patient with MDS into poor risk? (2)
inv(3)
-7
What cytogenetic abnormalities place a patient with MDS into very poor risk?
> 3 abnormalities
What is the prognostic tool used in MDS? What cutoff is used for high/low risk?
IPSS-R
<3.5 is low risk, >3.5 is high risk
You have patient with low risk MDS with isolated symptomatic anemia. What are the two preferred treatment options?
ESAs
Luspatercept (with RS or SF3B1 mut)
Luspatercept mechanism of action
SMAD2/3
What is the indication for luspatercept?
Low risk MDS with ringed sideroblasts or SF3B1 mutation
What is the treatment of choice for MDS-5q-?
Lenalidomide
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?
Lenalidomide (off label)
Best treatment for low-risk MDS with isolated thrombocytopenia?
Thrombopoietin agonists
Patient with low-risk MDS and isolated thrombocytopenia, no longer responds to TPO agonists. What is preferred treatment?
Hypomethylating agent
You have a patient with low-risk MDS with isolated thrombocytopenia. Who should you be very cautious in giving a TPO agonist to?
Excess blasts
Preferred treatment options (2) for low risk MDS with multilineage dysplasia?
HMAs (Decitabine or Azacitidine)
ATG (best for hypoplastic MDS)
Preferred treatment for high-risk MDS who are not HCT candidate? (2)
Azacitidine (Decitabine didn’t have any OS benefit)
Cedazuridine/Decitabine
Preferred treatment for high-risk MDS?
HCT, if they are a candidate
How do you diagnose MDS?
At least one cytopenia
Dysplasia >10% in at least one lineage
Marrow usually hypercellular
Clinical characteristics of MDS/MPN with neutrophilia?
Marrow dysplasia
Leukocytosis with left shift
<20% blasts
N BCR/ABL or PDGFRA rearrangements
No monocytosis
What mutations are associated with MDS/MPN with neutrophilia?
SETBP1, ASXL1, RAS, CSF3R
How do CSF3R mutations affect the management of MDS/MPN with neutrophilia?
Proximal mutation (T615A, T618I): responds to ruxolitinib
Distal mutations: respond to dasatinib
What mutation is commonly seen in MDS with ringed sideroblasts?
SF3B1
What are the 5 components of IPSS-R?
Cytogenetics, bone marrow blasts, hemoglobin, platelets, ANC
What are the most commonly mutated (3) genes in CHIP?
DNMT3a
TET2
ASXL1
What is the difference between ICUS and CCUS?
CCUS has a clonal mutation in myeloid related genes. Neither have diagnostic criteria for MDS, or any malignancy.
Treatment for CHIP?
Observation
In someone with therapy-related MDS from previous anthracycline or etoposide chemotherapy, what is the characteristic chromosomal abnormality?
11q23
Typical latency of therapy related MDS from RT or alkylating agents?
5-10 years
What is a way to predict a patients response to ESAs?
Low EPO has a higher likelihood of response
What is the appropriate time for transplant in MDS?
High risk: immediately
Low risk: at progression (after ESAs, Luspatercept, len, etc.)
Treatment of a patient with CMML and PDGFRB mutation?
Imatinib
In therapy-related MDS from previous treatment with alkylating agents, what are the commonly seen chromosomal abnormalities?
Monosomy 5 or 7
What is the WHO definition of MDS-IB1?
in BM:
5-9% blasts
no Auer rods
What is the WHO definition for MDS-IB2?
In BM:
10-19% blasts
Auer rods
Preferred treatment for high risk MDS with 5q deletion?
Still transplant or azacitadine
Len is only for low risk
For how long do you treat a high risk MDS patient with an HMA?
until failure or toxicity.
Even with a good response, stopping HMA is associated with earlier relapse and poorer prognosis
