MDS facts Flashcards by Erez Halperin

Incidence of MDS

3-4/100K

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IPSS-R in MDS

Hb < 10, 8
PLT < 100, 50
ANC < 800
Blasts> 2, 5, 10
Cytogentics

Most pts are old so age is not a risk factor

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IPSS-M in MDS

Hb, PLT, ANC
Blasts
Cytogenetics
Molecular data

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Cytogenetic risk in MDS

-Y, del 11- very good
Normal, del(5), del(12), del(20)- good
del(7), +8, +19, i(17p)- intermediate
-7, inv(3)/t(3q),del(3q), complex (3 abnormalities)- poor
> 3 abnormalities- very poor

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Important mutations in MDS

P53
MLL
FLT3
EZH2
ASXL1
TET2
RUNX1
U2AF1
NRAS

SF3B1- favorable

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ICUS

Cytopenia with no dysplasia and no clonality
Usually resolves spontaneously

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CCUS

cytopenia with no dysplasia with clonal somatic mutations
carries a higher risk to develop MDS/AML
consider clinical trial

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CHIP

Clonal mutations without cytopenias
carries a small risk for AML development

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Luspatercept vs EPO in LR-MDS

COMMANDS trial
Luspa has better transfusion independence rates (60% vs 30%)
Mainly in SF3B1/ RS

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Lenalidomide effectiveness in low risk MDS

In del(5q)
70% transfusion independence

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Timing of Len Tx in low risk MDS

Possibly before transfusion dependence
May reduce the need for future transfusions and maybe OS

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Tx with HMAs in low risk MDS

Use low doses and short (5 days a month) courses
Mainly when multilnge dysplasia
Usually, after luspa or EPO failure
Not approved in EMA

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Imetelstat in low risk MDS

Telomerase inhibitor
iMERGE trail
Phase III
vs placebo
Effective in pts who failed EPO
~40% TI

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Oral decitabine-cedazuridine vs IV decitabine in high risk MDS

ASCERTAIN trial
Phase III
Included CMML
Also in p53
Same PK and PD
60% ORR 21% CR

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AZA Tx for high risk MDS

AZA-001
compared to BSC
OS advantage!!!
24 months vs 15 months

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AZA +- Ven for high risk MDS

VERONA trial
no results yet

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VEXAS

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic
UBA1 gene
Men over 50
Fever, cytopenias, inflammation, thrombosis
Tx is with steroids, JAK2i, HMA, and transplant

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Dysplasia threshold in MDS

10%

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Copper deficiency presentation

Post bariatric surgery
MDS +
Myelopathy/neuropathy

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MDS with del5q clinical menifistations

Anemia
Thrombocytosis!
Megakaryocytes with monolobated nuclei

Defined as del5 with only one other cytogenetic abnormality, except monosomy 7 or del(7q).

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Significance of LGL/PNH clones in MDS

Better response to immunosuppressive therapy

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LR-PSS in MDS

A prognostic model to find poor risk pts with low risk MDS
Age, TD, cytogenetics found to be important

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IPSS-R in MDS cutofff

3.5
Above is considered high risk

Factors related to response to TPO-RAs in MDS

TPO<500
Low risk
Limited PLT transfusions

TPO-RAs in high risk MDS

ASPIRE trial Less thrombocytopenia but same rate of bleeding May induce proliferation of blasts in high risk pts

Deferasirox effectiveness in low risk MDS

Improves EFS and composite outcome that included OS

When to start iron chelation in low risk MDS

After 20-30 PC Usually ferritin > 1000

Deferasirox precautions

PO Hepatic/renal impairment GI bleeding Decreased hearing

Luspatercept effectiveness in low risk MDS

COMMANDS trial Phase III vs EPO Primary end point of TI Effective in SF3B1 mutated and maybe also in all low risk MDS

Non HMA option for LR MDS pts with MLD

ATG+prednisone 50% ORR

% with ctogenetic abnormalities in MDS

50%

Risk factors for progression of CCUS to AML

High VAF More than 1 mutation IDH1 p53

Median age MDS

76 >90% above 50

% with genetic mutations in MDS

90%

MDS with fibrosis

BM blasts 5-19%

Erythroid MDS changes

Ring sidroblasts>15% Megaloblastic changes Multinuclear Cytoplasmmic fraying

TET2 in MDS

Good prognosis

Tx of HR MDS that progressed on vidaza

Add venetoclax

Response to AZA in p53 MDS

Also respond

Tx of CCUS

Clinical trial Vitamin C may be effective

Worst mutations in CCUS

p53 IDH2 almost 100% will develop AML

GATA2 deficiency syndrome

MDS/AML at age 20 Autism ADHD Hearing loss Thrombosis

Prevalence of germline DDX41

1.5% of MDS/AML Most common familial disorder in adults Older age

Diagnosis of Fanconi anemia

Chromosome breakage in PB or skin

Lenalidomide in 5q MDS

10 mg Early cytopenias are positive predictive markers for response Rapid and sustained responses

EPO SE

HTN Headache VTE Arthralgia Rash N/V

Differences between IPSS and IPSS-R

IPSS-R puts more significance on cytogenetic changes and has a different blast percentage cutoff

MDS defining abnormalities (dysplasia not mandatory)

SF3B1 del5q >5% blasts Usually dysplasia is present but it is not mandatory

Fanconi anemia diagnosis

Chromosome breakage Preferably from fibroblast But usually from PB

Benefit of chelation in MDS

Maybe OS But non randomized studies And composite outcome of moratilty and iron overload

IDUS

Idiopathic dysplasia unknown significance Dysplasia without cytopenias or clonality

IDUS

Idiopathic dysplasia unknown significance Dysplasia without cytopenias or clonality

MDS classification WHO

MDS with defining genetic abnormalities (5q, SF3B1, p53) MDS morphological defined (low, IB1, IB2, hypoplastic, fibrosis)

MDS classification ICC

5q, SF3B1, p53 Single dysplasia, multilineage dysplasia, no dysplasia, EB, MDS/AML

Common CHIP mutation in smokers

ASXL1