1. Peripheral T Cell Lymphoma Prognostic Factors
Dennis D. Weisenburger, M.D.
for the
International PTCL Study

2. Prognostic Factors Histologic type – ALCL,ALK+ good
International Prognostic Index (IPI)
Clinical features – B symptoms, β2-microglobulin, bulky disease, etc;
Pathologic features – transformed cells, proliferation, EBV infection, etc;

3. International PTCL Study
Purpose
To assess the clinical applicability and reproducibility of the new WHO classification of peripheral T-cell and
NK-cell lymphomas

4. Case Selection
Previously-untreated adult patients (>19 yrs) with de novo peripheral T-cell or NK/T-cell lymphoma,
excluding mycosis fungoides and Sézary syndrome
Initial presentation between January 1, 1990, and December 31, 2002
Consecutive cases representative of the geographic region
Tissue biopsies adequate for diagnosis and classification
Clinical features, treatment and follow-up information

5. International PTCL Study
Study Sites Number Cases %
North America
6 sites
333
25.2
Europe
7 sites
452
34.2
Far East
8 sites
535
40.6

6. International PTCL Study Contributing Sites
North America – Omaha, Vancouver, Bethesda, Boston, Los Angeles, Tucson
Europe – Barcelona, Madrid, London, Oslo, Lyon, Wuerzburg, Bologna
Far East – Seoul, Hong Kong, Singapore, Bangkok, Tokyo, Nagoya, Okayama, Fukuoka

7. Overall Survival by diagnosis group 1.0 0.9 0.8 0.7 0.6 Proportion 0.5
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time
Diagnosis
CENSOR
FAIL
TOTAL
MEDIAN
Adult T-cell leuk/lymph (ATLL) 23
103
126
0.79
Anaplastic large cell lymphoma, ALK- 38 33 71
4.49
Anaplastic large cell lymphoma, ALK+ 63 27 90 .
Angioimmunoblastic T-cell lymphoma 87
154
241
2.26
Peripheral T-cell lymphoma
112
218
330
2.01
Generic NK-cell 49 85
134
0.65

8. Overall Survival by diagnosis group 1.0 0.9 0.8 0.7 0.6 Proportion 0.5
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13
Time
Diagnosis
CENSOR
FAIL
TOTAL
MEDIAN
Enteropathy-type T-cell lymphoma 9 52 61
0.88
Hepatosplenic T-cell lymphoma 3 16 19
0.67
Subcutaneous panniculitis-like T-cell ly 7 5 12
6.19
Primary cutaneous ALCL 20 3 23 .

9. Overall Survival
Nasak NK/T and Nasal-type NK/T and Aggressive/Unclass. NK/T
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12
Time
Diagnosis
CENSOR
FAIL
TOTAL
MEDIAN
Nasal NK/T-cell lymphoma 42 50 92
1.61
NK/T-cell lymphoma, nasal type 5 29 34
0.36
Unclassifiable or Aggressive NK-cell leu 2 6 8
0.23

10. Survival in PTCL correlates with IPI Scores
5 yr. OS
IPI 0-1
IPI 3-5
Cutaneous ALCL
90%
86% 5%
ALCL, ALK+
71%
51%
29%
Panniculitis-like
64%
42%
58%
ALCL, ALK-
49%
41%
39%
Nasal NK/T

11. Survival in PTCL Correlates with IPI Scores
5 yr. OS
IPI 0-1
IPI 3-5
PTCL-NOS
32%
28%
37%
Agioimmunoblastic
14%
59%
Enteropathy-type
20%
25%
45%
ATLL
19%
48%
Extranasal NK/T 9%
26%
60%
Hepatosplenic 7%
16%
84%

12. Consensus Diagnoses Cases % % T-cell PTCL, unspecified 340 25.8 29.3
Angioimmunoblastic
243
18.4
21.0
NK/T-cell
136
10.3
11.7
ATLL
126
9.5
10.9
ALCL, ALK+ 92
7.0
8.0
ALCL, ALK- 72
5.5
6.2

13. Overall Survival Disease Category: Peripheral T-cell lymphoma by IPI
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
IPI
CENSOR
FAIL
TOTAL
MEDIAN
0/1 40 47 87
5.11 2 38 72
110
2.1 3 19 51 70
1.41
4/5 9 39 48
0.67

14. Overall Survival Disease Category: Peripheral T-cell lymphoma
by Marrow Involvement
1.0
0.9
Test: p=0.027
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Bone marrow involvement
CENSOR
FAIL
TOTAL
MEDIAN no 87
159
246
2.11
yes 20 52 72
1.12

15. Overall Survival Disease Category: Peripheral T-cell lymphoma by T-IPI
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
T-IPI
CENSOR
FAIL
TOTAL
MEDIAN 31 33 64
4.68 1 42 76
118
2.1 2 25 65 90
1.46
3/4 8 35 43
0.7

16. Clinical Features of PTCL-NOS
IPI
0/1
28%
PIT
20% 2
35% 1
38% 3
22%
29%
4/5
15%
3/4
13%

18. Overall Survival Disease Category: Peripheral T-cell Lymphoma-NOS
by Transformed T-cell counts
1.0
0.9
Test: p=0.0078
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Median transformed T-cell count
CENSOR
FAIL
TOTAL
MEDIAN
<=30% 37 49 86
3.23
31-70% 33 56 89
2.03
>70% 19 60 79
1.23

19. Overall Survival Disease Category: Peripheral T-cell Lymphoma-NOS
by Ki67+ cells
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Ki67+ cells (%)
CENSOR
FAIL
TOTAL
MEDIAN
<=25% 25 27 52
5.26
26-75% 35 68
103
1.89
>75% 12 44 56
1.36

20. Overall Survival PTCL-US vs. PTCL-LE 1.0 0.9 0.8 0.7 0.6 Proportion
Test: p=0.0032
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Diagnosis
CENSOR
FAIL
TOTAL
MEDIAN
PTCL, unspecified 88
204
292
1.83
PTCL, lymphoepithelioid variant 18 10 28
17.2

21. Clinical Features of PTCL-US and PTCL-LE
IPI 0/1
18%
23% 2
35%
38%
0.87
3-5
37%
39%
Mass >10 cm 7% 0%
0.38
Platelets <150K
24%
29%
0.62
Transformed
cells >70%
33% 6%
0.03

22. Final Multivariate Analysis of Prognostic Factors in PTCL-NOS
Controlling for IPI HR P=
OS Transformed cells >70%
2.2
0.0002
FFS Transformed cells >70%
1.6
0.014
Controlling for PIT
OS Mass >10 cm
2.1
0.04
Platelets <150K
1.7
Transformed cells >70%
1.9
0.002
FFS Platelets <150K
0.02

23. Overall Survival Peripheral T-cell Lymphoma-NOS, and
Disease sub-group: Angioimmunoblastic T-cell lymphoma
1.0
0.9
Test: p=0.89
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time
Diagnosis
CENSOR
FAIL
TOTAL
MEDIAN
Angioimmunoblastic T-cell lymphoma 87
154
241
2.26
Peripheral T-cell lymphoma-NOS
112
218
330
2.01

24. Clinical Prognostic Factors of PTCL-NOS vs. Angioimmunoblastic (AI)
IPI scores 3-5
37%
59%
<0.0001
B symptoms
35%
69%
Hgb <11g/dl
22%
40%

25. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma
by IPI
1.0
0.9
Test: p=0.096
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Time
IPI
CENSOR
FAIL
TOTAL
MEDIAN
0/1 15 15 30
5.94 2 23 39 62
2.93 3 22 45 67
1.67
4/5 18 44 62
1.37

26. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma
by patient age
1.0
0.9
Test: p=0.036
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time
Age
CENSOR
FAIL
TOTAL
MEDIAN
<=60 40 60
100
3.21
>60 47 94
141
1.68

27. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma
by performance status
1.0
0.9
Test: p=0.0022
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time
Performance status
CENSOR
FAIL
TOTAL
MEDIAN
Ambulatory 63 85
148
3.1
Non-ambul. 22 67 89
1.37

28. Overall Survival Disease Sub-group: Angioimmunoblastic T-cell lymphoma
by B-symptoms
1.0
0.9
Test: p=0.0046
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time
B symptoms
CENSOR
FAIL
TOTAL
MEDIAN no 36 38 74
4.8
yes 51
116
167
1.62

29. Overall Survival Disease Sub-group: Angioimmunoblastic T-cell lymphoma
by Platelet Count
1.0
0.9
Test: p=0.017
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Time
Platelet Count
CENSOR
FAIL
TOTAL
MEDIAN
<150K/cmm 19 41 60
1.03
>=150K/cmm 52 90
142
2.4

30. Overall Survival Disease Category: Angioimmunoblastic
by Transformed T-cell counts
1.0
0.9
Test: p=0.14
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Time
Median transformed T-cell count
CENSOR
FAIL
TOTAL
MEDIAN
<=30% 47 72
119
2.4
31-70% 25 51 76
1.52
>70% 5 13 18
1.76

31. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma
by UNMC-IPI2
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Time
UNMC-PI2: Age / Perf. Stat / Plt Ct<150k
CENSOR
FAIL
TOTAL
MEDIAN 8 7 15
6.03 1 20 32 52
4.26 2 33 45 78
1.68 3 9 37 46
1.37 4 1 9 10
0.51

32. Overall Survival
Disease Sub-group: Anaplastic large cell lymphoma, ALK+
by IPI
1.0
0.9
0.8
Test: p<0.001
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Time
IPI
CENSOR
FAIL
TOTAL
MEDIAN
0/1 31 4 35 . 2 12 6 18 . 3 4 7 11
0.6
4/5 4 6 10
1.73

33. Overall Survival
Disease Sub-group: Anaplastic large cell lymphoma, ALK+
by Hemoglobin
1.0
0.9
Test: p=0.043
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Time
Hemoglobin
CENSOR
FAIL
TOTAL
MEDIAN
<11 g/dl 8 6 14 .
>=11 g/dl 32 9 41 .

34. Overall Survival
Disease Sub-group: Anaplastic large cell lymphoma, ALK-
by IPI
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time
IPI
CENSOR
FAIL
TOTAL
MEDIAN
0/1 22 5 27 . 2 8 4 12 . 3 5 11 16
1.71
4/5 2 8 10
0.66

35. Conclusions Histologic type is a good predictor of survival
IPI is a good predictor of survival in PTCL-NOS along with % of transformed cells
IPI is a poor predictor of survival in angioimmunoblastic type and better prognostic models are needed
IPI is a good predictor of survival in ALCL,ALK+ (along with Hgb <11g/dl) and ALCL,ALK-

36. Conclusions
IPI is useful for stratification of most PTCL patients for risk-adapted therapies
New clinical, pathological and molecular genetic predictors are needed to develop more biologically-relevant prognostic models for the various disease entities