Cytogenetic analysis in Hematological Malignancies

25
Cytogenetic Analysis in Hematological Malignancies Hwei-Fang Tien, National Taiwan University Hospital

description

 

Transcript of Cytogenetic analysis in Hematological Malignancies

Page 1: Cytogenetic analysis in Hematological Malignancies

Cytogenetic Analysis in

Hematological Malignancies

Hwei-Fang Tien, National Taiwan University Hospital

Page 2: Cytogenetic analysis in Hematological Malignancies

Recurrent chromosomal abnormalities in Hematological malignancies

Abnormalities important for classification CML t(9;22)

AML t(8;21), t(15;17), inv(16), t(9;11), inv(3), t(6;9), t(1;22), -5/5q-, -7/7q-

ALL t(4;11), t(1;19), t(v;11q23), t(12;21) *

MDS -Y, del(11q); del(5q), del(12p), del(20q); del(7q), +8, +19, i(17q); -7, inv(3)

Lymphoma DLBCL t(3q27)

Burkitt t(8;14) and variant

Follicular t(14;18)

Mantle cell t(11;14)

Marginal zone t(11;18), t(1;14), t(14;18)

Page 3: Cytogenetic analysis in Hematological Malignancies

Purpose of Cytogenetic Study in Hematological malignancies

1. Diagnosis and classification

2. Risk stratification

3. Selection of proper treatment

4. Follow-up of the response

Page 4: Cytogenetic analysis in Hematological Malignancies

Case Demonstration

Diagnosis

Page 5: Cytogenetic analysis in Hematological Malignancies

BM smears in a patient with thrombocytopenia and anemia

NTUH, Gene Chromosome Cancer, 1995,12:161

Page 6: Cytogenetic analysis in Hematological Malignancies
Page 7: Cytogenetic analysis in Hematological Malignancies

Cytogenetic Abnormalities

NTUH, Gene Chromosome Cancer, 1995,12:161Final dignosis: hepatosplenic Tγ/δ lymphoma

Page 8: Cytogenetic analysis in Hematological Malignancies

Large granular lymphocytosis

Br J Haematol, 1998, 103:1124

Cytogenetic Abnormalities

Diagnosis: NK-cell large granular lymphocyte leukemia

PB smears

Page 9: Cytogenetic analysis in Hematological Malignancies

BM aspirate smears from a patient with pancytopenia

Page 10: Cytogenetic analysis in Hematological Malignancies

Hypoplastic MDS

Page 11: Cytogenetic analysis in Hematological Malignancies

Name: 林 X 榮 , 46, XY, -7 [20]

Chromosomal abnormality

Diagnosis: hypoplastic MDSLeukemia, 2008, 22:544

Page 12: Cytogenetic analysis in Hematological Malignancies

Case Demonstration

For Lymphoma Staging

Page 13: Cytogenetic analysis in Hematological Malignancies

BM study for staging in a patients with DLBCL

BM biopsy: no lymphoma involvement

BM smears

Page 14: Cytogenetic analysis in Hematological Malignancies
Page 15: Cytogenetic analysis in Hematological Malignancies

Same Clonal Chromosomal Abnormalities in Lymph Node as in Bone Marrow

Lymph node Bone marrow

Lymphoma involvement of BM is confirmed

Page 16: Cytogenetic analysis in Hematological Malignancies

Risk Stratification

Page 17: Cytogenetic analysis in Hematological Malignancies

Impact of Cytogenetics in AML based on 2008 WHO Classification

Medical Research Council , United Kingdom Blood. 2010;116(3):354 , Blood Rev, 2011; 25:39

t(9;22)-7/7q--5/5q-Inv(3), t(3;3)

t(9;11)t(3;5)t(6;9)MDS-relatedother t(11q23)

t(15;17)

t(8;21)Inv(16)

5876 patients

Normal

Page 18: Cytogenetic analysis in Hematological Malignancies

Cytogenetic Scoring System in MDS (n=2,754)

Abnormality Overall survival

AML transformation

Prognostic Subgroup

No. ofPts

% Single Double Cplx Median(months)

Median (months)

Very good 81 2.9 del(11q), -Y ― ―

60.8 NR

Good (reference)

1,809 65.7 Normal, del(5q)del(12p), del(20q)

Including del(5q)

48.6 NR

Intermediate 529 19.2 del(7q), +8, i(17q)+19, any otherIndependent clones

Any other ―

26.0 78.0

Poor 148 5.4 Inv(3)/t(3q)/del(3q),-7

Including-7/del(7q)

3 15.8 21.0

Very poor 187 6.8 ― ― > 3 5.9 8.2

Abbreviations: AML, acute myeloid leukemia; NR, not reached.

Schanz et al, J Clin Oncol, 2012

Page 19: Cytogenetic analysis in Hematological Malignancies

MM: Impact of genomic aberrations on OS

Blood. 2007;109:3489

Page 20: Cytogenetic analysis in Hematological Malignancies

Prognostic relevance of chromosome aberrations in CLL

Best Pract Res Clin Haematol. 2007 20:439

17p-

11q-

+12

13q- sole

normal

Page 21: Cytogenetic analysis in Hematological Malignancies

Follow Up the Clinical Course

Page 22: Cytogenetic analysis in Hematological Malignancies

Chronic Myeloid Leukemia, Chronic Phase

Page 23: Cytogenetic analysis in Hematological Malignancies

CML in acute transformation

Page 24: Cytogenetic analysis in Hematological Malignancies

Indication of Cytogenetic Study

• Unknown cause of cytopenia• Fever of unknown origin• WHO classification of AML and ALL• MDS diagnosis, classification (IPSS, IPSS-R)• Lymphoma diagnosis, classification and

staging work up• Risk stratification of CLL and MM• Follow-up of treatment response