Transcript TCD for assessment of stroke risk in SCD

CYTOGENERIC
ASSESSMENT
IN MDS
G-EXJ-1030713
May 2012
NOTE: These slides are for use in educational oral presentations only. If any published figures/tables from these slides are
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Specific local use requires local approval.
Outline
● MDS Classification and prognosis scoring
● Practical guide to bone marrow aspirate analysis in MDS
● Cytogenetics of MDS in bone marrow aspirates
● Summary
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LIC = liver iron concentration; MRI = magnetic resonance imaging;
SF = serum ferritin; SIR = signal intensity ratio;
SQUID = superconducting quantum interface device.
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 MDS
consensus, 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
•
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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.
Minimal diagnostic criteria in MDS
consensus, 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.
6
Loken MR, et al. Leuk Res. 2008;32:5-17. Van de Loosdrecht AA. Leuk Res. 2008;32:205-7.
G-EXJ-1030713 Van de Loosdrecht AA, et al. Blood. 2008;111:1067-77. Van de Loosdrecht AA, et al. Haematologica.
May 2012
2009;94:1124-1134. Nimer SD. Blood. 2008;111:4841-51. Valent P, et al. Leuk Res. 2007;31:727-36.
MDS classification
and prognostic
scoring
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Diagnostic and prognostic of MDS
Classification system
Basis of evaluation
Derived prognostic
score system
FAB (1982)
Cellular morphology
IPSS (1997)
WHO (2002)
Cellular morphology,
cytogenetics
WPSS (2007)
Risk-stratification is necessary for clinical decision-making:
● predicts treatment outcomes
● predicts survival
● predicts risk of progression to AML
FAB, French-American-British; IPSS, International Prognostic Scoring System; WPSS, WHO-based
8
Prognostic Scoring System.
G-EXJ-1030713 Bennett JM, et al. Br J Haematol 1982;51:189–199; Jaffe, et al, eds. Lyon: IARC Press; 2001; Greenberg
May 2012
P, et al. Blood 1997;89:2079–2088; Malcovati L, et al. J Clin Oncol 2007;23:3503–3510.
French-American-British (FAB) classification
Blast percentage
MDS
Subtype
Peripheral
blasts (%)
Bone marrow
blasts (%)
RA
Refractory anaemia
≤1
<5
RARS
Refractory anaemia
with ringed
sideroblasts
≤1
<5
RAEB
Refractory anaemia
with excess blasts
<5
5–20
Refractory anaemia
with excess blasts in
transformation
≥5
21–29
optional
Auer-rods
60–100
Chronic
myelomonocytic
leukaemia
<5
≤20
Peripheral
monocytosis
(>103/µl)
>40
RAEB-T
CMML
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Bennett JM, et al. Br J Haematol 1982;51:189–199.
Additional
features
AML
transformation (%)
10–20
>15% ringed
sideroblasts in
bone marrow
10–35
>50
Survival by cytogenetic presentation
in MDS patients
100
90
80
−Y
del(5q)
Normal
del(20q)
Misc. single
+8
Double
Misc. double
Chrom 7 abn.
Misc. complex
Complex
Survival (%)
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time (years)
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Greenberg P, et al. Blood. 1998;89:2079-88.
Patients
n
(%)
17
(2)
48
(6)
489
(69)
16
(2)
74
(9)
38
(5)
29
(3)
14
(2)
10
(1)
15
(2)
66
(8)
Risk stratification and
prognosis scoring for MDS: IPSS
IPSS score
Variable
BM blasts (%)
Karyotype
Cytopenia(s)
0
0.5
1.0
1.5
2.0
<5
5–10
–
11–20
21–30
Good
Int.
Poor
0/1
2/3
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
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Greenberg P, et al. Blood. 1998;89:2079-88.
Cumulative survival of MDS patients by IPSS
Survival
100
90
90
80
80
Percent
60
50
40
60
50
40
30
30
20
20
10
10
0
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0 2 4
6 8 10 12 14 16 18
Years
Greenberg P, et al. Blood 1997;89:2079–2088.
Low
Int-1
Int-2
High
70
Percent
Low
Int-1
Int-2
High
70
AML Evolution
100
0
0 2 4
6 8 10 12 14 16 18
Years
MDS: WHO classification 2008
Blast percentage
MDS
Subtype
Dysplasia
Peripheral
blasts (%)
Bone marrow
blasts (%)
Ringed
sideroblasts (%)
Cytogenetics
Mostly DysE
< 1%
< 5%
< 15%
5q− sole
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
5q− syndrome
RA, RN, RT, RCUD
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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.
Proportion surviving
Survival of MDS patients according to
transfusion dependency
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Transfusion-independent patients
Transfusion-dependent patients
0
20
40
60
80
Time (months)
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Cazzola M, Malcovati L. N Engl J Med. 2005;352:536-8.
100
120
140
The WHO classification-based prognostic
scoring system (WPSS) for MDS
Points
0
1
2
3
RA, RARS,
del(5q)
RCMD,
RCMD-RS
RAEB-1
RAEB-2
Transfusion requirement
None
Regular
–
–
Cytogenetic category
Good
Int.
Poor
–
WHO subtype
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
Transfusion dependence is an independent indicator of
severity of disease and has a significant effect on survival
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Malcovati L, et al. J Clin Oncol. 2007;25:3503-10.
Overall survival and AML risk assessments in
MDS by WPSS
Cumulative probability
of survival
C. Time-dependent overall survival (n=271)
1.0
0.9
Risk group
0.8
Very Low
0.7
Low
0.6
Intermediate
0.5
High
0.4
Very High
0.3
0.2
0.1
0 0 24 48 72 96 120 144 168 192 216 240
Time (months)
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Malcovati L et al. J Clin Oncol 2007;25:3503–3510.
B. Risk of AML at diagnosis (n=426)
Cumulative risk
1.0
Risk group
0.9
Very Low
0.8
Low
0.7
Intermediate
0.6
High
0.5
Very High
0.4
0.3
0.2
0.1
0 0 24 48 72 96 120 144 168 192 216 240
Time (months)
1.0
Risk group
0.9
Very Low
0.8
Low
0.7
Intermediate
0.6
High
0.5
Very High
0.4
0.3
0.2
0.1
0 0 24 48 72 96 120 144 168 192 216 240
Time (months)
D. Time-dependent risk of AML (n=271)
Cumulative risk
Cumulative probability
of survival
A. Overall survival at diagnosis (n=426)
1.0
0.9
Risk group
0.8
Very Low
0.7
Low
0.6
Intermediate
0.5
High
0.4
Very High
0.3
0.2
0.1
0 0 24 48 72 96 120 144 168 192 216 240
Time (months)
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
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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.
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
•
●
What tests are done?
–
assessment of cellularity, architecture and focal collection of blasts for hematopoietic
dysplasia
•
–
●
heparinized sample can be stored at room temperature for 24 hours
smear staining examination
cytogenetic analysis
•
karyotype
•
FISH
What other tests might be done?
–
flow cytometry
•
cell counts
•
cell sorting
•
immunophenotyping
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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.
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
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Hellström-Lindberg E. Myelodysplastic Syndromes. London: Remedica; 2008.
Analysis of bone marrow smears (cont.)
Refractory anaemia with
excess blasts (RAEB)
Refractory anaemia (RA)
Abnormal large megakaryocyte (double arrow),
abnormal hypo-granular and Pelger neutrophils
(single arrows).
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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.
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 identification
of blasts - CD34+/abnormal
granularity/CD45dim
● Well-correlated with other
diagnostic techniques and
prognostic systems
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Van de Loosdrecht, et al. Haematologica.2009; 94:1124-34.
Image from: http://www.bio.davidson.edu/courses/genomics/method/FACS.html
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
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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.
Cytogenetic aberrations are frequent
in patients with MDS
14%
N = 2,072 patients with MDS
9%
Normal karyotype
48%
One abnormality
Two abnormalities
Complex karyotype
29%
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Haase D, et al. Blood. 2007;110:4385-95.
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
Unbalanced aberrations with loss of genetic information (deletions or
monosomies) are most common in MDS; balanced aberrations are rare
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Swerdlow SH, et al. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.
4th ed. Lyon: IARC; 2008:441.
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)
•
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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.
FAQs: Cytogenetic testing for
diagnosis of patients with MDS
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).
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Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.
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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Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.
FAQs: Cytogenetic testing during treatment in
patients with MDS (cont.)
How often should cytogenetic testing be performed?
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.
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.
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.
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Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.
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
Storage
●
●
Collect at least
10–20 mL of
heparinized
BM aspirates
Metaphase quality
● To detect structural abnormalities,
adequate chromosome banding
is required (≥ 150–250 bands
per karyogram)
6
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7
8
9
See presenter for references.
Samples should
reach the lab
within 24 hours
after biopsy
Number of metaphases needed
●
10
Analyse 25 metaphases
if possible, especially if
the karyotype is normal,
to exclude a small aberrant
cell clone
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
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Holland and Frei. Cancer Medicine 6. American Cancer Society; 2003.
Lucia Cytogenetics. http://www.lucia.cz/en/products/lucia-karyo. Accessed Feb.2011.
FAQs: Karyotyping
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).
What are the limitations of this method?
Need for dividing cells; cell clones < 10% of abnormal cells can be overlooked; submicroscopic abnormalities
cannot be detected.
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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.
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
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Images from: http://www.wikidoc.org/index.php/Chronic_myelogenous_leukemia. Accessed Feb.2011.
Preparation of the FISH sample
Metaphase slides for karyotyping
could 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
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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Image from: http://www.creative-biolabs.com/fish/tissuearray5.htm. Accessed Feb. 2011
Protocol from: labs.mmg.pitt.edu/gjoerup/FISH%20protocol%20Vysis.doc. Accessed Feb. 2011.
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, 20q
Genzyme
Genetics
www.genzymegenetics.com
5p/q, 7q, 17p13, 20q13
Kreatech
www.kreatech.com
5p/q, 7cen/q, 8cen, 17p13, 20q13, Ycen
Abbott
Molecular
www.abbottmolecular.com
5/5q, 7/7q, 20q
Metasystems
www.metasystemsinternational.com
Selection of the FISH probes is essential part of the analysis
and is typically done by clinical geneticists in cooperation with hematologists
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*Examples are not representative of the complete spectrum of probes available from each provider.
1Cherry AM, et al. Blood. 2010;116:[abstract 2922].
FAQs: FISH
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.
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1Cherry
AM, et al. Blood. 2010;116:[abstract 2922].
Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.
FAQs: FISH (cont.)
What probes should be used for survival prognosis?
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 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).
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Questions and answers were prepared under the review of Dr. Haase, University of Göttingen, Germany.
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
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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
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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
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