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NCCN > MDS > Flashcards

MDS Flashcards

1
Q

This should be done if standard cytogenetics (with ≥20 metaphases) cannot be obtained

A

Chromosome microarray analysis (CMA; also known as chromosome genomic array testing [CGAT]) or

MDS-related fluorescence in situ hybridization (FISH) panel

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2
Q

If karyotype is normal, this shoud be done

A

Chromosome microarray analysis (CMA; also known as chromosome genomic array testing [CGAT])

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3
Q

Able to detect not only somatic but also constitutional (germline) changes.

A

Chromosome microarray analysis (CMA; also known as chromosome genomic array testing [CGAT])

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4
Q

A more representative measure of folate stores

A

RBC folate

The preferred test to serum folate

RBC folate levels are more indicative of folate stores, whereas serum folate levels are reflective of recent nutrition.

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5
Q

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

A

Serum methylmalonic acid testing

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6
Q

Mineral deficiency can mimic many of the peripheral blood and marrow findings seen in MDS.

A

Copper

Copper and ceruloplasmin level assessments should be considered as part of the initial diagnostic workup in patients suspected of having low-risk MDS, especially those with gastrointestinal (GI) disorders and neuropathy

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7
Q

Clinical features associated with copper deficiency include :

A
  • Vacuolation of myeloid and/or erythroid precursors
  • Prior GI surgery
  • A history of vitamin B12 deficiency
  • Severe malnutrition
  • A history of zinc supplementation
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8
Q

A differential for MDS , in patients <40 years of age that is due to disordered mitochondrial heme synthesis, often with distinctive mutational and clinical features.

Some of these patients will have disease that responds to pyridoxine or thiamine.

A

Congenital sideroblastic anemia (CSA)

CSA is not MDS

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9
Q

TRUE OR FALSE

Flow cytometric evaluation of blast percentage can be a substitute for morphologic evaluation

A

FALSE

The percentage of marrow myeloblasts based on morphologic assessment (aspirate smears preferred) should be reported.

Flow cytometric estimation of blast percentage should not be used as a substitute for morphology in this context.

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10
Q

AML-DEFINING GENETIC ABNORMALITIES: WHO 2022 AND ICC

Even if marrow blast percentage is less than 20

A
  • t(8;21)(q22;q22.1)/RUNX1::RUNX1T1
  • inv(16)(p13.1q22) or t(16;16) (p13.1;q22)/CBFB::MYH11
  • t(9;11)(p21.3;q23.3)/MLLT3::KMT2A
  • Other KMT2A rearrangements
  • t(6;9)(p22.3;q34.1)/DEK::NUP214
  • inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2; MECOM(EVI1)
  • Other MECOM rearrangements
  • Mutated NPM1
  • CEBPA (WHO only), in-frame bZIP CEBPA mutations (ICC only)
  • RBM15::MRTFA fusion (WHO only)
  • NUP98 rearrangement (WHO only)
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11
Q

The most frequently mutated genes associated with CHIP.

A

DNMT3A, TET2, ASXL1, RUNX1, JAK2, PPM1D, TP53, and splicing factor genes

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12
Q

Mutations are commonly found in T-cell LGL (T-LGL) disease.

A

STAT3

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13
Q

Used to assess presence of PNH clone

A

FCM analysis of granulocytes and monocytes from blood with FLAER (fluorescent aerolysin) and at least one glycophosphatidylinositol anchored protein

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14
Q

Preferred risk categorization

A

IPSS-R

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15
Q

3 variable in IPSS Scoring System

A
  • Marrow blast percentage
  • Cytogenetic subgroup
  • Number of cytopenias
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16
Q

Developed by investigators at the MD Anderson Cancer Center, is a prognostic model used in the evaluation of MDS, and was designed to help identify patients with lower-risk disease (IPSS low or int-1) who may have a poor prognosis.

A

Lower-Risk Prognostic Scoring System (LR-PSS)

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17
Q

Immunosuppressive therapy can be usful in

A
  • Patients generally ≤60 y and with ≤5% marrow blasts
  • Those with hypocellular marrows
  • PNH clone positivity
  • STAT3-mutant cytotoxic T-cell clones.

IST includes equine antithymocyte globulin (ATG) ± cyclosporin A.

Additionally, for severe thrombocytopenia, eltrombopag alone could be considered.

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18
Q

Treatment failure would be considered if no response within _______ months.

A

3–6 months

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19
Q

Preferred regimen for MDS-5q (low blasts): del(5q) ± one other cytogenetic abnormality (except those involving chromosome 7) IPSS Low/Intermediate-1

**regardless of serum EPO

A

Lenalidomide

Other recommended regimens if Serum EPO ≤500 mU/mL:
Epoetin alfa
Darbepoetin alfa

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20
Q

Preferred regimen for MDS-SF3B1 (low blasts): No del(5q) ± other cytogenetic abnormalities with RS ≥15% (or RS ≥5% with an SF3B1 mutation)

A

Luspatercept-aamt

GCSF pag EPO < 5 00
Ivosidenib pag IDH1 and EPO> 500

Other recommended regimens if NO RESPONSE

Serum EPO ≤500 mU/mL:
Epoetin alfa
Darbepoetin alfa
Epoetin alfa + G-CSF
Darbepoietin alfa + G-CSF

Serum EPO>500 mU/mL:
Lenalidomide
Ivosidenib

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21
Q

Preferred regimen for No del(5q) ± other cytogenetic abnormalities with RS <15% (or RS <5% with an SF3B1 mutation) with serum EPO ≤500 mU/mL

A

Epoetin alfa
Darbepoetin alfa

If no response:
* Add GCSF
* Shift to Luspatercept

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22
Q

Preferred regimen for: No del(5q) ± other cytogenetic abnormalities with RS <15% (or RS <5% with an SF3B1 mutation) with serum EPO >500 mU/mL

Good probability to respond to IST

A

ATG + cyclosporin A
ATG + cyclosporin A + eltrombopag

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23
Q

Preferred regimen for: No del(5q) ± other cytogenetic abnormalities with RS <15% (or RS <5% with an SF3B1 mutation) with serum EPO >500 mU/mL

Poor probability to respond to IST

A

Azacitadine

Other Recommended
* Decitabine
* Oral decitabine and cedazuridineaa
Useful in Certain Circumstances
Consider lenalidomide

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24
Q

Dosing of Azacitidine

A

75 mg/m2/day SC for 7 days every 28 days for at least six courses

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25
Q

TRUE OR FALSE

Survival benefit with AzaC has only been demonstrated using the 5-day schedule.

A

FALSE

Survival benefit with AzaC has only been demonstrated using the 7-day schedule.

  • An alternative 5-day schedule of AzaC has been evaluated, both as an SC regimen (including the 5-2-2 schedule: 75 mg/m2/day SC for 5 days followed by 2 days of no treatment, then 75 mg/m2/day for 2 days, every 28 days; and the 5-day schedule: 75 mg/m2/day SC for 5 days every 28 days) and as an IV regimen (75 mg/m2/day IV for 5 days every 28 days)
  • Although response rates with the 5-day regimens appeared similar to the approved 7-day dosing schedule
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26
Q

Optimal dosing for Decitabine

A

20 mg/m2/day IV for 5 days

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27
Q

Could be a substitution for intravenous decitabine in patients with IPSS Intermediate-1 and above.

A

Oral decitabine and cedazuridine (DEC-C)

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28
Q

Assessment of response with:
Azacitidine:
Decitabine:

A

Azacitidine: after 6 cycles
Decitabine: after 4 cycles

29
Q

Recommended lenalidomide initial dose is:

A

10 mg/day for 21 out of 28 days or 28 days monthly for 2–4 months

  • Lenalidomide 10 mg daily if absolute neutrophil count >0.5, platelets >50,000
  • Use caution for patients with low platelet and neutrophil counts; consider modifying lenalidomide dose.
  • Lenalidomide exposure has been associated with a selective expansion of TP53-mutated clones
30
Q

Dosing for:
Epoetin alfa:

Darbepoetin alfa:

A

Epoetin alfa: 40,000–60,000 U 1–2 times per week subcutaneously (SC)

Darbepoetin alfa: 150–300 mcg every other week SC

At some institutions, darbepoetin alfa has been administered using doses up to 500 mcg every other week.

31
Q

The starting dose of luspatercept-aamt is:

A

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)

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)

32
Q

Target hemoglobin range:

A

10 to 12 g/dL

Not to exceed 12 g/dL

33
Q

Nonrespose to Luspatercept-aamt

A

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.

34
Q

Nonrespose to ESA

A

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.

35
Q

Preferred regimen for: Highrer risk MDS Non-transplant candidate

A

Azacitidine

Other recommended regimens:
* Decitabine
* Decitabine + cedazuridine

Subsequent treatment
* Ivosidenib

36
Q

Iron chelation is recommemded if >________ 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).

A

> 20 to 30 RBC transfusions

For patients with serum ferritin levels >2500 ng/mL, aim to decrease ferritin levels to <n1000 ng/mL

Patients with low creatinine clearance (<40 mL/min) should not be treated with deferasirox or deferoxamine.

37
Q

TRUE OR FALSE

Proliferative CMML (white blood cell [WBC] count >12,000/mm3) has a worse prognosis than the dysplastic subtype.

A

TRUE

Proliferative CMML (white blood cell [WBC] count >12,000/mm3) has a worse prognosis than the dysplastic subtype.

38
Q

MDS/MPN CLASSIFICATION

A
  • Chronic myelomonocytic leukemia (CMML) | CMML-1 CMML-2
  • Atypical chronic myeloid leukemia (aCML) (BCR::ABL negative) | MDS/MPN and neutrophilia
  • MDS/MPN with ring sideroblasts (RS) and thrombocytosis (T) | MDS/MPN with mSF3B1 and thrombocytosis
  • MDS/MPN unclassifiable (MDS/MPN-U) | MDS/MPN not otherwise specified (NOS)
  • Juvenile myelomonocytic leukemia (JMML)
39
Q

MDS/MPN CLASSIFICATION

≥0.5 absolute monocyte count (AMC)
≥10% monocytes
Clonality

A

Chronic myelomonocytic leukemia (CMML)

80%–90% with ≥1 mutation in SRSF2, TET2, and/or ASXL1. Substantial frequency of SETBP1, NRAS/KRAS, RUNX1, CBL, and EZH2 mutations.

CMML has been subdivided into two groups based on molecular and clinical differences:
* proliferative-type CMML (WBC count ≥13 x 109/L) and
* dysplastic type CMML (WBC count <13 x 109/L)

40
Q

MDS/MPN CLASSIFICATION

  • WBC ≥13K
  • dysplastic granulocytosis
  • ≥10% granulocytic precursor cells
  • mSETBP1 ± mASXL1
A

Atypical chronic myeloid leukemia (aCML) (BCR::ABL negative)

41
Q

MDS/MPN CLASSIFICATION

Platelets ≥450K

A

MDS/MPN with ring sideroblasts (RS) and thrombocytosis (T)

42
Q

MDS/MPN CLASSIFICATION

Platelets ≥450K or WBC ≥13K

A

MDS/MPN unclassifiable (MDS/MPN-U)

43
Q

MDS/MPN CLASSIFICATION

> 90% RAS pathway activation abnormality

A

Juvenile myelomonocytic leukemia (JMML)

44
Q

Cytogenetic risks:

Very good

A
  • -Y
  • del(11q)
45
Q

Cytogenetic risks:

Good

A
  • Normal
  • del(5q)
  • del(12p)
  • del(20q)
  • double including del(5q)
46
Q

Cytogenetic risks:

Intermediate

A
  • del(7q)
  • +8
  • +19
  • i(17q)
  • Any other single or double independent clones
47
Q

Cytogenetic risks:

Poor

A
  • -7
  • inv(3)/t(3q)/del(3q)
  • double including -7/del(7q)
  • complex: 3 abnormalities
48
Q

Cytogenetic risks:

Very poor

A
  • complex: >3 abnormalities
49
Q

Cytopenias in MDS is defined as:

A
  • Neutrophil count <1,800/mcL
  • Platelets <100,000/mcL
  • Hb <10 g/dL
50
Q

Genes frequently mutated in MDS

A
  • TET2 20%–25%
  • SF3B120%–30%
51
Q

Genes associated with:

Complex karyotypes:
Excess bone marrow blast proportion:
Severe thrombocytopenia:
Response to HMA:

A

Complex karyotypes: TP53
Excess bone marrow blast proportion: RUNX1, NRAS, and TP53
Severe thrombocytopenia: RUNX1, NRAS, and TP53
Response to HMA:TET2

52
Q

Whom to test for Suspected Hereditary Myeloid Malignancy Predisposition Syndromes (HMMPS)

A
  • Allogeneic related donor HCT candidate of patients with suspected HMMPS
  • All patients with MDS and adults <50 y with AML
  • Clinically suspected genetic predisposition syndrome at any age
  • “Hypocellular MDS”
  • Newly diagnosed aplastic anemia
  • Personal history of MDS or AML (including therapy-related) and ≥1 additional cancer(s)
53
Q

Clinically suspected genetic predisposition syndrome at any age

A
  • Personal history of congenital anomalies and/or other manifestations concerning for an HMMPS, including so-called inborn errors of immunity (eg, early-onset and/ or multiple cancers, excessive toxicity with chemotherapy or radiation, hypocellular marrow, poor stem cell mobilizer, unexplained cytopenias or macrocytosis, pulmonary and/or liver fibrosis, immune deficiency/dysregulation ± laboratory findings of humoral and/or cellular immunodeficiency).
  • Relative with one or more of the following: acute leukemia or MDS or other manifestations (see above bullet) concerning for an HMMPS.
  • Member of a family with a genetically defined HMMPS.
54
Q

The recommended DNA source for germline testing in order to exclude somatic mutations and to avoid false negatives due to peripheral blood/marrow somatic mosaicism or somatic genetic reversion events.

A

Cultured skin fibroblasts

55
Q

Supplemental laboratory testing for: Fanconi anemia (FA)

A

Chromosome breakage analysis

56
Q

Supplemental laboratory testing for: Shwachman-Diamond syndrome

A

Serum pancreatic isoamylase (pediatric and adult patients) and serum trypsinogen (pediatric patients)

low

57
Q

Supplemental laboratory testing for: Short telomere syndromes, such as dyskeratosis congenita

A

Fluorescence in situ hybridization (FISH) assays using leukocyte subsets

Demonstrate shortened telomere lengths

Although in older patients telomere length results may not be sensitive or specific and may require complementary genetic evaluation to aid in interpretation.

58
Q

Supplemental laboratory testing for: Diamond-Blackfan anemia

A

Erythrocyte adenosine deaminase

Often elevated

59
Q

An International Consensus Working Group recommended that minimal diagnostic criteria for this disease include two prerequisites:

A
  • Stable cytopenia (for at least 6 months unless accompanied by a specific karyotype or bilineage dysplasia, in which case only 2 months of stable cytopenias are needed), and the
  • Exclusion of other potential disorders as a primary reason for dysplasia or cytopenia or both
60
Q

The diagnosis of MDS requires at least one of three MDS-related (decisive) criteria:

A
  • 1) dysplasia (≥10% in one or more of the three major bone marrow lineages)
  • 2) a blast cell count of 5% to 19%; and
  • 3) a specific MDS-associated karyotype [eg, del(5q), del(20q), +8, or -7/del(7q)]
61
Q

With a moderate degree of variability, patients with MDS-EB or MDS-EB-T generally have a relatively poor prognosis, with a median survival ranging from _______ months.

A

5 to 12 months

62
Q

Are defined by the presence of a clonal karyotypic abnormality (present in ≥2 metaphases) and/or a somatic mutation in a gene involved in hematopoiesis (present at >2% variant allele frequency)

A

Clonal hematopoiesis of indeterminate potential (CHIP)
Clonal cytopenia of undetermined significance (CCUS)

CCUS with cytopenia

63
Q

The most frequently mutated genes associated with CHIP include:

A
  • DNMT3A
  • TET2
  • ASXL1
  • RUNX1
  • JAK2
  • PPM1D
  • TP53
  • SF
64
Q

Mutations that have positive predictive values for myeloid neoplasms (ie, MDS, MPN, AML)

A
  • Patients with pathogenic mutations with >10% variant allelic frequency and ≥2 somatic mutations
  • Spliceosome gene mutations
  • Mutations of RUNX1 or JAK2

Isolated mutations of DNMT3A, TET2, and ASXL1 have less predictive value

65
Q

Have no known cause, lack somatic mutations or clonal karyotypic abnormalities, and differ from each other only by the presence of cytopenia or marrow dysplasia, respectively

A

Idiopathic cytopenia of undetermined significance (ICUS)
Idiopathic dysplasia of unknown significance (IDUS)

66
Q

The 2008 WHO classification separates pediatric myeloproliferative diseases (MPDs) into three groups:

A
  • MDS (RCC, MDS-EB, MDS-EB-T, or AML with MDS-related changes)
  • Myelodysplastic disease/MPD (JMML); and
  • Down syndrome disease (transient abnormal myelopoiesis and myeloid leukemia of Down syndrome).
67
Q

The most common subtype of MDS found in children, accounting for approximately 50% of cases.

A

RCC

68
Q

The most common cytogenetic abnormality, occurring in 30% of cases of pedriatic MPDs

A

Monosomy 7

Followed by trisomy 8 and trisomy 21

69
Q

Major candidates for HMAs:

A
  1. Patients with IPSS int-2– or high-risk disease; or
  2. IPSS-R intermediate-, high-, or very-high-risk disease with any of the following criteria:
  • Patients who are not candidates for high-intensity therapy
  • Patients who are potential candidates for allogeneic HCT but for whom delay in receipt of that procedure is anticipated (eg, due to need to further reduce the blast count, improve patient performance status, or identify a donor). In these circumstances, the drugs may be used as a bridging therapy for that procedure
  • Patients who are not expected to respond to (or who relapsed after) ESAs or IST.

NCCN (13 decks)

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