Myelodysplastic syndrome Flashcards
Lab profile (features of anemia and other thrombocytopenias)
- 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
Indications for treatment of lower risk MDS
1) Requiring frequent transfusions
Initial therapy for intermediate-2/high-risk MDS
IF non candidate for HSCT → azacitidine or until disease progression or intolerable side effects
IF candidate → AlloHSCT
pathophysiology of MDS
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.
venetoclax mechanism
Blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells.
Management of patient with clinically significant anemia
1) measure epo. if below 500, give epo.
What are the hypomethylating agents?
azacetadine or decitabine
Risk stratification score used for MDS
Revised International Prognostic Scoring System (IPSS-R)
General diagnosis of MDS
1) Cytopenias
2) Low blast percentage in marrow
3) Morphologic evidence of dysplasia
Workup of suspected MDS
- **peripheral smear
- bone marrow aspirate and biopsy
MDS-SLD means
MDS-single lineage dysplasia (1 or 2 cytopenias, but other cell lines are normal)
What are the dysplastic cells you may see on peripheral smear indicating MDS?
≥10 percent of erythroid precursors, granulocytes, or megakaryocytes
Diagnostic criteria
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
what does CHIP stand for?
- clonal hematopoiesis of indeterminate potential
what does risk stratification depend on?
- percentage of bone marrow blasts
- number and severity of cytopenias
- cytogenetic findings
Examples of lower-intensity treatments
- epoetin alfa
- thrombopoietin receptor agonists
- neupogen
- luspatercept
- hypomethylating agents (HMA; eg, azacitidine, decitabine)
- immunosuppressive therapy, lenalidomide
- targeted agents (eg, IDH inhibitors).
Actionable mutation in MDS
IDH1 or IDH2
Adverse genetic features in MDS
1) TP53 mutation
2) adverse cytogenetic abnormalities
Management of high risk MDS patient
IF adverse genetic features present, HSCT is preferable
IF not, then targeted therapy with IDH1 agent is preferable
IF no IDH1, then transplant
what are the IDH inhibitor drugs?
enasidenib and ivosidenib
procrit generic name
EPO
Marrow in MDS
- typically hypercellular but can be hypocellular (hypocellular MDS)
how to determine expected cellularity of marrow in a patient
cellularity = 100 - age
Most favorable mutation
SF3B1
FDA approved drug for MDS w/ ring sideroblasts
luspatercept
Combination therapy approved for MDS
decitabine and cedazuridine (inqovi)
WHO categories for MDS
MDS with single lineage dysplasia MDS with multilineage dysplasia MDS with ring sideroblasts MDS with excess blasts MDS with isolated del(5q)
NCCN preferred/category 1 HMA for higher risk
azacitadine
Role for IDH inhibitors
Ongoing research, second line (confirm, not sure)
Dysplastic features on smear or marrow aspirate suggesting MDS
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
When is lenalidomide used in MDS
5q deletion, low and intermediate risk MDS, with anemia
what are the IPSS-R risk categories?
- low
- intermediate-1
- intermediate-2
- high
- very high
Staging system for MDS
IPSS-R
Number of blasts required for MDS with excess blasts-1
5-9%
Number of blasts required for MDS with excess blasts-2
10-19%
Auer rods in MDS?
You can have auer rods in MDS-EB2
*Not all auer rods are APML
frequency of chromosomal translocations in MDS vs. AML
less common in MDS
Management of patient with characteristics AML cytogenetic abnormalities (8;21, 15;17, inversion 16)
3+7 chemotherapy
Indication for lenalidomide
Transfusion-dependent patients with low or intermediate-1 MDS + 5q deletion
duration of azacitadine in MDS
Continue until progression or unacceptable toxicity (data shows interruption of HMAs is associated with earlier relapse and poor prognosis)
why azacitidine vs. decitabine
- haven’t been compared head to head
- only aza has demonstrated a survival benefit, so it is in guidelines
azacitidine and decitabine formulation
- aza = can also be PO or IM
- decitabine is IV
Variables included in IPSS-R
1) cytogenetics
2) blasts
3) hgb
4) plt
5) ANC
trade name for azacitadine
vidaza
what is inqovi
Oral combination of decitabine + cedazuridine
Preferred HMA for non-transplant candidates
azacitidine
generic name for aranesp
darbopoeitin
Treatment durations for HMAs with MDS
- 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)
Can MDS be cured?
Allogeneic hematopoietic stem cell transplantation is the only curative therapy for MDS
Worst mutation to have in MDS
TP53
What is CCUS?
clonal mutation + cytopenia BUT doesn’t meet WHO criteria for a heme neoplasm
Target hgb range in MDS
10
Very good cytogenetic findings in MDS
Deletion Y, del 11
