G-EXJ-1030713 May 2012 CYTOGENERIC ASSESSMENT IN MDS NOTE: These slides are for use in educational...

G-EXJ-1030713May 2012

CYTOGENERICASSESSMENTIN MDS

NOTE: These slides are for use in educational oral presentations only. If any published figures/tables from these slides are to be used for another purpose (e.g. in printed materials), it is the individual’s responsibility to apply for the relevant permission. Specific local use requires local approval.

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Outline

● MDS Classification and prognosis scoring

● Practical guide to bone marrow aspirate analysis in MDS

● Cytogenetics of MDS in bone marrow aspirates

● Summary

LIC = liver iron concentration; MRI = magnetic resonance imaging;SF = serum ferritin; SIR = signal intensity ratio;SQUID = superconducting quantum interface device.

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What are the myelodysplastic syndromes (MDS)?

● MDS are a spectrum of heterogeneous myeloid clonal disorders

● Occurrence:

– De novo (primary MDS)

– Secondary or treatment-related MDS

● MDS are associated with significant morbidity and mortality due to:

– Risk of transformation to acute myeloid leukemia (AML)

– Cytopenias

– Impaired quality of life (frequent transfusions, iron overload, etc)

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Common features of MDS

● MDS are marked by ineffective haematopoiesis and defective development of blood cells, e.g.:

– dyserythropoiesis (affects red blood cells production)

– dysgranulopoiesis (affects granulocytes production)

– dysmegakaryopoiesis (affects platelet production)

● Ineffective haematopoiesis and maturation of the blood cells results in one or more cytopenias, e.g.:

– anaemia (reduced red blood cell count)

– neutropenia (reduced absolute neutrophil count)

– thrombocytopenia (reduced number of platelets)

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Minimal diagnostic criteria in MDSconsensus, Vienna 2006

● Prerequisite criteria– constant cytopenia in one or more cell lineages

• complete blood count – exclusion of all other causes of cytopenia / dysplasia

● MDS-related (decisive) criteria

– dysplasia in > 10% of all bone marrow cells in one or more of the lineages, or > 15% ringed sideroblasts• complete blood count • iron staining of bone marrow smears

– 5–19% blast cells • bone marrow smears

– typical chromosomal abnormality• karyotyping or FISH

FISH = fluorescence in situ hybridization.Loken MR, et al. Leuk Res. 2008;32:5-17. Nimer SD. Blood. 2008;111:4841-51. Valent P, et al. Leuk Res. 2007;31:727-36.

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Minimal diagnostic criteria in MDSconsensus, Vienna 2006 (cont.)

● Additional criteria (for patients not fulfilling the decisive MDS criteria)

– abnormal phenotype of bone marrow cells

• flow cytometry

– molecular signs of a monoclonal cell population

• HUMARA assay, gene chip profiling, point mutation or SNP analysis

– markedly and persistently reduced colony formation

• CFU assay

CFU = colony-forming unit;SNP-a = single-nucleotide polymorphism.Loken MR, et al. Leuk Res. 2008;32:5-17. Van de Loosdrecht AA. Leuk Res. 2008;32:205-7.Van de Loosdrecht AA, et al. Blood. 2008;111:1067-77. Van de Loosdrecht AA, et al. Haematologica. 2009;94:1124-1134. Nimer SD. Blood. 2008;111:4841-51. Valent P, et al. Leuk Res. 2007;31:727-36.

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MDS classification and prognostic scoring

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Diagnostic and prognostic of MDS

Risk-stratification is necessary for clinical decision-making:

● predicts treatment outcomes

● predicts survival

● predicts risk of progression to AML

Classification system Basis of evaluation Derived prognostic score system

FAB (1982) Cellular morphology IPSS (1997)

WHO (2002) Cellular morphology, cytogenetics WPSS (2007)

FAB, French-American-British; IPSS, International Prognostic Scoring System; WPSS, WHO-based Prognostic Scoring System. Bennett JM, et al. Br J Haematol 1982;51:189–199; Jaffe, et al, eds. Lyon: IARC Press; 2001; Greenberg P, et al. Blood 1997;89:2079–2088; Malcovati L, et al. J Clin Oncol 2007;23:3503–3510.

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French-American-British (FAB) classification

Blast percentage

MDS Subtype

Peripheral blasts (%)

Bone marrow blasts (%)

Additional features

AML transformation (%)

RA Refractory anaemia ≤1 <5 10–20

RARSRefractory anaemia

with ringed sideroblasts

≤1 <5>15% ringed

sideroblasts in bone marrow

10–35

RAEB Refractory anaemia with excess blasts

<5 5–20 >50

RAEB-TRefractory anaemia

with excess blasts in transformation

≥5 21–29optional

Auer-rods60–100

CMMLChronic

myelomonocytic leukaemia

<5 ≤20Peripheral

monocytosis (>103/µl)

>40

Bennett JM, et al. Br J Haematol 1982;51:189–199.

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Survival by cytogenetic presentation in MDS patients

Su

rviv

al (

%)

100

90

80

70

60

50

40

30

20

10

0

Time (years)

0 1 2 3 4 5 6 7 8 9 10 1112 13 14 15 1617 18

Patients

n (%)

−Y 17 (2)

del(5q) 48 (6)

Normal 489 (69)

del(20q) 16 (2)

Misc. single 74 (9)

+8 38 (5)

Double 29 (3)

Misc. double 14 (2)

Chrom 7 abn. 10 (1)

Misc. complex 15 (2)

Complex 66 (8)

Greenberg P, et al. Blood. 1998;89:2079-88.

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Risk stratification and prognosis scoring for MDS: IPSS

Influence of karyotype according to IPSS

● Good = normal, −Y, del(5q), del(20q)

● Poor = complex (≥ 3 abnormalities) or chromosome 7 anomalies

● Int. = all other abnormalities

Variable 0 0.5 1.0 1.5 2.0

BM blasts (%) < 5 5–10 – 11–20 21–30

Karyotype Good Int. Poor

Cytopenia(s) 0/1 2/3

Greenberg P, et al. Blood. 1998;89:2079-88.

IPSS score

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Years

Cumulative survival of MDS patients by IPSS

Low

Int-1

Int-2

High

0 2 4 6 8 10 14 16 180

10

20

30

40

50

60

70

80

90

100Survival

Years

Per

cen

t

0 2 4 6 8 10 14 16 180

10

20

30

40

50

60

70

80

90

100

Per

cen

t

AML Evolution

Low

Int-1

Int-2

High

Greenberg P, et al. Blood 1997;89:2079–2088.

12 12

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MDS: WHO classification 2008

Blast percentage

MDS Subtype

DysplasiaPeripheral blasts (%)

Bone marrow blasts (%)

Ringedsideroblasts (%)

Cytogenetics

5q− syndrome Mostly DysE < 1% < 5% < 15% 5q− sole

RA, RN, RT, RCUD DysE, N, T < 1% < 5% < 15% Various

RARS Mostly DysE 0 < 5% > 15% Various

RCMD 2–3 lineages rare < 5% < 15% Various

RAEB-1 1–3 lineages < 5% 5–9% < 15% Various

RAEB-2 1–3 lineages 5–19%Auer rods +/-

10–19%Auer rods +/-

< 15% Various

MDS-U 1 lineage < 1% < 5% < 15% Various

BM = bone marrow; DysE = dyserythropoiesis; MDS-U = myelodysplastic syndrome, unclassified; N = neutropenia; pB = peripheral blood; RCMD = refractory cytopenia with multilineage dysplasia; RCUD = refractory cytopenia with unilineage dysplasia; RN = refractory neutropenia;RT = refractory thrombocytopenia; T = thrombocytopenia. Swerdlow SH, et al., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008:109-38.

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Survival of MDS patients according to transfusion dependency

Transfusion-dependent patients

Transfusion-independent patients

Time (months)

Pro

po

rtio

n s

urv

ivin

g

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 20 40 60 80 100 120 140

Cazzola M, Malcovati L. N Engl J Med. 2005;352:536-8.

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The WHO classification-based prognostic scoring system (WPSS) for MDS

Points

0 1 2 3

WHO subtypeRA, RARS,

del(5q)RCMD,

RCMD-RSRAEB-1 RAEB-2

Transfusion requirement None Regular – –

Cytogenetic category Good Int. Poor –

Risk groups Score Median survival (months)

Very low 0 103

Low 1 72

Intermediate 2 40

High 3–4 21

Very high 5–6 12

Malcovati L, et al. J Clin Oncol. 2007;25:3503-10.

Transfusion dependence is an independent indicator of severity of disease and has a significant effect on survival

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Overall survival and AML risk assessments in MDS by WPSS

Malcovati L et al. J Clin Oncol 2007;25:3503–3510.

A. Overall survival at diagnosis (n=426) B. Risk of AML at diagnosis (n=426)

C. Time-dependent overall survival (n=271) D. Time-dependent risk of AML (n=271)

1.00.90.80.70.60.50.40.30.20.1

0

1.00.90.80.70.60.50.40.30.20.1

0

1.00.90.80.70.60.50.40.30.20.1

0

1.00.90.80.70.60.50.40.30.20.1

0

Cu

mu

lati

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rob

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ty

of

surv

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Cu

mu

lati

ve r

isk

Cu

mu

lati

ve p

rob

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ty

of

surv

ival

Cu

mu

lati

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isk

Time (months) Time (months)

Time (months) Time (months)

Risk groupVery LowLowIntermediateHighVery High




0 24 48 72 96 120144 168 192 216 240

0 24 48 72 96 120144 168 192 216 240

0 24 48 72 96 120144 168 192 216 240

0 24 48 72 96 120144 168 192 216 240

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WHO prognosis scoring system allows time dependent prognosis scoring

IPSS WPSS

Pros • More widely used and recognized

• Allows time-dependent prognosis scoring and risk stratification

• Takes into account individual patient transfusion need

Cons • Applies only at the time of diagnosis

• Underestimates the impact of transfusion requirement and cytogenetics

• Underestimates the impact of poor cytogenetics

Greenberg P, et al. Blood 1997;89:2079–2088. Malcovati L, et al. J Clin Oncol. 2007;25:3503–3510.Schanz J, et al. Blood. 2007;110:[abstract 248]. Kantarjian H, et al. Cancer. 2008;113:1351-61.Garcia-Manero G, et al. Leukemia. 2008;22:538-43.

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Practical guide to bone marrow aspirate analysis in MDS

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Bone marrow biopsy

● How is it done:– Marrow aspirate and bone (trephine) biopsy are removed by physician in an outpatient

procedure under local anesthesia• heparinized sample can be stored at room temperature for 24 hours

● What tests are done?– assessment of cellularity, architecture and focal collection of blasts for hematopoietic

dysplasia• smear staining examination

– cytogenetic analysis• karyotype• FISH

● What other tests might be done?– flow cytometry

• cell counts• cell sorting• immunophenotyping

Hellström-Lindberg E. Myelodysplastic Syndromes. London: Remedica; 2008. Van de Loosdrecht, et al, Haematologica.2009; 94:1124-34. Image from: Medline Plus. NIH/NLM. http://www.nlm.nih.gov/medlineplus/ency/imagepages/1129.htm. Accessed Jan, 2011.

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Analysis of bone marrow smears

● Bone marrow aspirate smears are prepared on a slide by a medical technician using:

– Wright’s stain

– Perl’s staining (for ringed sideroblasts)

– May-Grünwald-Giemsa staining

– Immunohistochemical stainings, i.e. CD34

● A pathologist or hematologist then examines the slides for cell abnormalities under microscope:

– at least 400 nucleated cells and 20 megakaryocytes should be examined for morphology

Hellström-Lindberg E. Myelodysplastic Syndromes. London: Remedica; 2008.

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Abnormal large megakaryocyte (double arrow), abnormal hypo-granular and Pelger neutrophils

(single arrows).

Refractory anaemia (RA)

Analysis of bone marrow smears (cont.)

Refractory anaemia with excess blasts (RAEB)

Erythroid cells with peri-nuclear iron accumulation Prussian blue staining (left); Perl’s stain showing

ringed sideroblasts with peri-nuclear (mitochondrial) deposition of iron (right)

ASH Image Bank, used with permission, all rights reserved.Courtesy of J. Goasguen, Université de Rennes, France.

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Immunophenotyping by flow cytometry

● Various lineages are labeled with antibodies that recognize specific haematopoeitic identifiers

● Combination of no more than four labels recommended

● Important for identificationof blasts - CD34+/abnormalgranularity/CD45dim

● Well-correlated with other diagnostic techniques and prognostic systems

Van de Loosdrecht, et al. Haematologica.2009; 94:1124-34.Image from: http://www.bio.davidson.edu/courses/genomics/method/FACS.html

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Cytogenetics of MDS in bone marrow aspirates

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Importance of cytogenetic analysis in MDS

● Nearly half of the patients with MDS present with cytogenetic abnormalities1

– changes have a pathogenetic relevance (i.e. loss or gain of gene function)

● Cytogenetic analysis is essential for the diagnosis and classification of MDS according to IPSS and WPSS2

● Chromosomal aberrations have prognostic relevance for OS and for the time to leukaemic transformation, independent of other factors

● Cytogenetic analysis forms the basis for therapeutic decisions

– cytogenetics is indicative of response to therapy, i.e. lenalidomide in del(5q)3 and azacitidine in −7/del(7q)4

IPSS = International Prognostic Scoring System; OS = overall survival; WPSS = WHO classification-based Prognostic Scoring System.1Haase D, et al. Blood. 2007;110:4385-95. 2Greenberg P, et al. Blood. 1998;89:2079-88. 3List AF, et al. N Engl J Med. 2006;355:1456-65. 4Fenaux P, et al. Lancet Oncol. 2009;10:223-32.

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Cytogenetic aberrations are frequent in patients with MDS

9%

14%

29%

48%

Normal karyotype

One abnormality

Two abnormalities

Complex karyotype

N = 2,072 patients with MDS

Haase D, et al. Blood. 2007;110:4385-95.

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WHO 2008: Incidence of the most common cytogenetic aberrations in MDS (over 5%)

Unbalanced aberrations De novo MDS (%)

Secondary MDS (%)

+8 10

−7/del(7q) 10 50

−5/del(5q) 10 40

del(20q) 5–8

−Y 5

iso(17q)/t(17p)/del(17p) 3–5

Swerdlow SH, et al. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC; 2008:441.

Unbalanced aberrations with loss of genetic information (deletions or monosomies) are most common in MDS; balanced aberrations are rare

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When should cytogenetic testing be performed in patients with MDS: Diagnosis

● WHO 2008 guidelines recommend a complete cytogenetic analysis of BM at initial diagnosis in all patients with MDS

● Cytogenetic analysis is mandatory for

– diagnosis of MDS associated with del(5q)

– patients with refractory cytopenia(s) who lack MDS diagnostic features; these patients may be considered as having presumptive evidence of MDS if they have MDS-related cytogenetic abnormalities (slides 4 and 5)

• rather than indicating abnormality, isolated loss of Y chromosome might be an age-related phenomenon and mosaicism with trisomy 8 might be a constitutional change. Therefore, they might not be sufficient to prove MDS

BM = bone marrow.Swerdlow SH, et al. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC; 2008:441. Valent P, Horny HP. Eur J Clin Invest. 2009;39:548-53. Vardiman JW, et al. Blood. 2009;114:937-51.

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Is cytogenetic testing required for all patients?

Yes, cytogenetic testing should be performed whenever possible at initial diagnosis and every 6–12 months during follow-up since karyotype and prognosis might change during the course of the disease. There are a few exceptions that will have no therapeutic consequences, e.g. very frail and multi-morbid patients.

Are there disease presentations that correlate with specific cytogenetic abnormalities?

There is no correlation between specific abnormalities and disease presentation (with exception of the association between isolated del(5q) syndrome and RA, with typical dysplasia of megakaryocytes).

FAQs: Cytogenetic testing for diagnosis of patients with MDS

Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.

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FAQs: Cytogenetic testing during treatment in patients with MDS

Why is it important to perform cytogenetic testing during the treatment course?

Cytogenetic remissions represent a better quality of remission and are more reliable than those determined by blood films or cytomorphology from the BM. Furthermore, karyotype might change during the course of the disease affecting the prognosis and the treatment of the patient. First data show that a cytogenetic progression might be detectable several weeks before clinical manifestation.

Is cytogenetic testing important for all patients or is it recommended for specific focus groups?

All patients with clonal abnormalities identified before start of therapy should be followed up during therapy. Also, patients with initially normal karyotype might develop abnormalities during the course of disease and, therefore, require regular monitoring.


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Cytogenetics from BM is recommended when possible at least once every 6 months during therapy. When FISH is performed using peripheral blood (i.e. CD34-FISH), testing should be conducted every 3rd month.

How often should cytogenetic testing be performed?

When should treatment be altered as a result of changes in the cytogenetic profile?

When a clear cytogenetic progression is seen, or when an abnormal clone is completely eliminated and karyotype turns normal and stays normal over time (at least 3 months); this depends on the type of therapy.

What is the definition of cytogenetic progression in MDS?

1) Occurrence of new cytogenetic abnormalities (first in patients with normal karyotype or additional for patients with abnormalities).

2) Significant increase (> 50%) of the size of the clone with certain cytogenetic abnormalities.

FAQs: Cytogenetic testing during treatment in patients with MDS (cont.)


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Chromosome analysis in MDS: Karyotyping

● Each cell in the body contains 46 chromosomes representing the normal human karyotype

● MDS patients frequently have a clonal abnormality in the hematopoietic progenitor cells, where a proportion of these have an abnormal karyotype with altered number of chromosomes and/or large alterations in their structure

– Changes in the number of the chromosomes is due to monosomies (loss of a chromosome) and/or polysomies (more then 2 copies of a chromosome)

– Changes in the structure of the chromosomes are commonly noted as:

• deletions, when part or entire chromatid is missing

• insertions, when additional material is included in a chromosome

• translocations, when genetic material is exchanged between chromosomes

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How to perform cytogenetic testing in patients with MDS: Karyotyping

Sample

● Collect at least 10–20 mL ofheparinized BM aspirates

Storage

● Samples shouldreach the lab within 24 hours after biopsy

Number of metaphases needed

● Analyse 25 metaphases if possible, especially if the karyotype is normal, to exclude a small aberrant cell clone

6 7 8 9 10

Metaphase quality● To detect structural abnormalities,

adequate chromosome banding is required (≥ 150–250 bands per karyogram)

See presenter for references.

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How to perform cytogenetic testing in patients with MDS: Karyotyping (cont.)

● Medical technician prepares metaphase slides for karyotyping, by:

– culturing bone marrow aspirate for 24-72 hours, and then

– exposing the cells to slightly hypotonic solution

– synchronizing them in metaphase (e.g. using colchicine)

– finally, staining them (e.g. DAPI staining) and fixing them on slides

● A pathologist or hematologist then examines the slides for chromosomal abnormalities under microscope:

– Samples are examined under microscope manually or with aid of analysis software (separating, enhancing banding pattern, chromosome pairing)

– At least 25 metaphases should be examined, especially if the karyotype is normal, to exclude a small aberrant cell clone

Holland and Frei. Cancer Medicine 6. American Cancer Society; 2003.Lucia Cytogenetics. http://www.lucia.cz/en/products/lucia-karyo. Accessed Feb.2011.

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Can peripheral blood be used?

Peripheral blood is usually not an alternative. No BM available: attempt banding analysis from peripheral blood (CD34-FISH), especially when blasts are present. Metaphase yield from peripheral blood is generally worse than that from BM aspirates. CD34-FISH can be an option.1

What sample-related factors could influence the accuracy of the test?

Ex-vivo time over 24 hours: clotting; bacterial/fungal contamination; and low cellular content (e.g. hypocellular BM, or if several syringes are filled during biopsy and the last syringe is used for banding analysis).

Need for dividing cells; cell clones < 10% of abnormal cells can be overlooked; submicroscopic abnormalities cannot be detected.

What are the limitations of this method?

FISH = fluorescent in situ hybridization.1Braulke F, et al. Leuk Res. 2010;34:1296-301.Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.

FAQs: Karyotyping

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Chromosome analysis in MDS: Fluorescence in situ hybridization (FISH)

● Fluorescently labeled DNA probes recognize complementary sequences on the chromosomes

– probes that recognize centromeres detect changes in the number of chromosomes

– probes that recognize specific genes can detect changes in the chromosome sequence

Fluorescently labeled probes for bcr and abl

genes show exchange of DNA between

Chromosomes in chronic myelogenous leukemia

Images from: http://www.wikidoc.org/index.php/Chronic_myelogenous_leukemia. Accessed Feb.2011.

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Preparation of the FISH sample

Metaphase slides for karyotypingcould also use bone marrow smears and

paraffin-embedded bone marrow biopsies)

Denature DNA (heat up the sample)

Hybridize with denatured (pre-heated) labeled probes

Wash to remove excess probe

DAPI stain for DNA

View with fluorescence microscope and take photographs

Image from: http://www.creative-biolabs.com/fish/tissuearray5.htm. Accessed Feb. 2011Protocol from: labs.mmg.pitt.edu/gjoerup/FISH%20protocol%20Vysis.doc. Accessed Feb. 2011.

Preparation of the FISH could be done by trained medical technician or clinical geneticist.

The analysis of the samples is carried by clinical geneticists and/or hematologists.

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FISH: Selection of probes

● MDS FISH panel for initial diagnosis detects the most common aberrations, and typically includes probes for 5q, 7q, #8, 11q, 12p, 13q, 17p, and 20q

Probes* Manufacturer Web site

Multiprobe MDS/AML panel Cytocell www.cytocell.com

5/5q, 7/7q, 8cen, 20qGenzyme Genetics

www.genzymegenetics.com

5p/q, 7q, 17p13, 20q13 Kreatech www.kreatech.com

5p/q, 7cen/q, 8cen, 17p13, 20q13, YcenAbbott Molecular

www.abbottmolecular.com

5/5q, 7/7q, 20q Metasystemswww.metasystems-international.com

Selection of the FISH probes is essential part of the analysis and is typically done by clinical geneticists in cooperation with hematologists

*Examples are not representative of the complete spectrum of probes available from each provider.1Cherry AM, et al. Blood. 2010;116:[abstract 2922].

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How is a probe selected?

Use the standard MDS FISH panel for initial diagnosis. When the aberration is known/suspected, use additional probes in the region. If disease morphology is suggestive of a certain genotype, one could directly use the respective probe – e.g. if RA with typical dysplasia of megakaryocytes occurs, then use probes for del(5q). Note, however, that one can miss other genetic changes with this approach.

How many probes are typically used in a panel?

A standard panel consists of 7–8 probes.1 An extended panel can include up to 12 probes.

FAQs: FISH

1Cherry AM, et al. Blood. 2010;116:[abstract 2922].Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.

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The available survival data are based on karyotyping (banding) studies. However, in addition to karyotyping, one should use a standard FISH panel: 5p/q, 7cen/q, #8cen, 17p13, 20q13, and Ycen (in males).

What probes should be used for survival prognosis?

What are the limitations of FISH?

One sees/finds what one is looking for; therefore, one could overlook complex or rare abnormalities (e.g. finding an isolated del(5q) by FISH might give a false good prognosis if it is a part of a complex genotype that has been misidentified).

FAQs: FISH (cont.)


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Summary

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Summary

● WHO 2008 guidelines recommend complete cytogenetic analysis of BM at initial diagnosis of MDS

● Chromosomal aberrations, among other factors, have prognostic relevance on overall survival and time to leukaemic transformation

– IPSS was first to define cytogenetic risk groups and to show an association with the survival prognosis of the patient

– improved understanding of the cytogenetic risk factors provides a better prognosis scoring for the patients with MDS

● Approximately 50% of MDS patients have abnormal cytogenetics

– in addition, it is supposed that many patients with “normal cytogenetics” actually have clonal abnormalities that remain undetected by metaphase cytogenetics

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Summary (cont.)

● Cytogenetic analysis is essential for making therapeutic decisions with regard to patients with MDS as it has shown associations with the response to hypomethylating and immunomodulating agents

● Sequential cytogenetic analysis is recommended to improve clinical management in MDS

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GLOSSARY OF TERMS

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GLOSSARY

● AML = acute myeloid leukemia

● APFR = Atrialp peak filling rate

● BA = basilar artery

● ß-TM = Beta Thalassemia Major

● ß-TI = Beta Thalassemia Intermedia

● BM = bone marrow

● BTM = bone marrow transplantation

● BW = bandwidth

● CFU = colony-forming unit

● CMML = chronic myelomonocytic leukemia

● CT2 = cardiac T2*.

● DAPI = 4',6-diamidino-2-phenylindole

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GLOSSARY

● DFS = = disease-free survival.

● DysE = dyserythropoiesis

● ECG = electrocardiography

● EDV = end-diastolic velocity

● EF = ejection fraction

● EPFR = early peak filling rate

● FatSat = fat saturation

● FAQ = frequently asked questions

● FDA = Food and Drug Administration

● FISH = fluorescence in situ hybridization.

● FOV = field of view

● GBP = Currency, pound sterling (£)

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GLOSSARY

● Hb = hemoglobin

● HbE = hemoglobin E

● HbF = fetal hemoglobin

● HbS = sickle cell hemoglobin.

● HbSS = sickle cell anemia.

● HIC = hepatic iron concentration

● HU = hydroxyurea

● ICA = internal carotid artery.

● ICT = iron chelation therapy

● IDL = interface description language

● IPSS = International Prognostic Scoring System

● iso = isochromosome

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GLOSSARY

● LIC = liver iron concentration

● LVEF = left-ventricular ejection fraction

● MCA = middle cerebral artery

● MDS = Myelodysplastic syndromes

● MDS-U = myelodysplastic syndrome, unclassified

● MRA = magnetic resonance angiography

● MRI = magnetic resonance imaging

● MV = mean velocity.

● N = neutropenia

● NEX = number of excitations

● NIH = National Institute of Health

● OS = overall survival

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GLOSSARY

● pB = peripheral blood

● PI = pulsatility index

● PSV = peak systolic Velocity

● RA =refractory anemia

● RAEB = refractory anemia with excess blasts

● RAEB -T = refractory anemia with excess blasts in transformation

● RARS = refractory anemia with ringed sideroblasts

● RBC = red blood cells

● RF = radio-frequency

● RCMD = refractory cytopenia with multilineage dysplasia

● RCMD-RS = refractory cytopenia with multilineage dysplasia with ringed sideroblasts

● RCUD = refractory cytopenia with unilineage dysplasia

49G-EXJ-1030713May 2012

GLOSSARY

● RN = refractory neutropenia

● ROI = region of interest

● RT = refractory thrombocytopenia

● SCD = sickle cell disease

● SD = standard deviation

● SI = signal intensity

● SIR = signal intensity ratio

● SF = serum ferritin

● SNP-a = single-nucleotide polymorphism

● SQUID = superconducting quantum interface device.

● STOP = = Stroke Prevention Trial in Sickle Cell Anemia

● STOP II = Optimizing Primary Stroke Prevention in Sickle Cell Anemia

50G-EXJ-1030713May 2012

GLOSSARY

● T = thrombocytopenia

● TAMMV = time-averaged mean of the maximum velocity.

● TCCS = transcranial colour-coded sonography

● TCD = transcranial doppler ultrasonography

● TCDI = duplex (imaging TCD)

● TE = echo time

● TR = repetition time

● WHO = World Health Organization

● WPSS = WHO classification-based Prognostic Scoring System

G-EXJ-1030713 May 2012 CYTOGENERIC ASSESSMENT IN MDS NOTE: These slides are for use in educational...

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Transcript of G-EXJ-1030713 May 2012 CYTOGENERIC ASSESSMENT IN MDS NOTE: These slides are for use in educational...