Peripheral T Cell Lymphoma Prognostic Factors Dennis D
- Slides: 36
Peripheral T Cell Lymphoma Prognostic Factors Dennis D. Weisenburger, M. D. for the International PTCL Study
Prognostic Factors l Histologic type – ALCL, ALK+ good l International Prognostic Index (IPI) l Clinical features – B symptoms, β 2 microglobulin, bulky disease, etc; l Pathologic features – transformed cells, proliferation, EBV infection, etc;
International PTCL Study Purpose To assess the clinical applicability and reproducibility of the new WHO classification of peripheral T-cell and NK-cell lymphomas
Case Selection l Previously-untreated adult patients (>19 yrs) with de novo peripheral T-cell or NK/T-cell lymphoma, l excluding mycosis fungoides and Sézary syndrome l Initial presentation between January 1, 1990, and December 31, 2002 l Consecutive cases representative of the geographic region l Tissue biopsies adequate for diagnosis and classification l Clinical features, treatment and follow-up information
International PTCL Study Sites Number Cases % North America Europe 6 sites 333 25. 2 7 sites 452 34. 2 Far East 8 sites 535 40. 6
International PTCL Study Contributing Sites l North America – Omaha, Vancouver, Bethesda, Boston, Los Angeles, Tucson l Europe – Barcelona, Madrid, London, Oslo, Lyon, Wuerzburg, Bologna l Far East – Seoul, Hong Kong, Singapore, Bangkok, Tokyo, Nagoya, Okayama, Fukuoka
Overall Survival Proportion by diagnosis group 1. 0 0. 9 0. 8 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 0 Test: p<0. 001 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
Overall Survival by diagnosis group 1. 0 0. 9 Test: p<0. 001 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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 .
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 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Time Diagnosis Nasal NK/T-cell lymphoma, nasal type Unclassifiable or Aggressive NK-cell leu CENSOR FAIL TOTAL MEDIAN 42 50 92 1. 61 5 29 34 0. 36 2 6 8 0. 23
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 41% 49%
Survival in PTCL Correlates with IPI Scores 5 yr. OS IPI 0 -1 IPI 3 -5 PTCL-NOS 32% 28% 37% Agioimmunoblastic 32% 14% 59% Enteropathy-type 20% 25% 45% ATLL 14% 19% 48% Extranasal NK/T 9% 26% 60% Hepatosplenic 7% 16% 84%
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
Overall Survival Disease Category: Peripheral T-cell lymphoma by IPI 1. 0 0. 9 Test: p<0. 001 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Category: Peripheral T-cell lymphoma by Marrow Involvement 1. 0 0. 9 Test: p=0. 027 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Category: Peripheral T-cell lymphoma by T-IPI 1. 0 0. 9 Test: p<0. 001 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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 0 31 33 64 4. 68 1 42 76 118 2. 1 2 25 65 90 1. 46 3/4 8 35 43 0. 7
Clinical Features of PTCL-NOS IPI 0/1 28% 2 PIT 0 20% 35% 1 38% 3 22% 2 29% 4/5 15% 3/4 13%
Overall Survival Disease Category: Peripheral T-cell Lymphoma-NOS by Transformed T-cell counts 1. 0 0. 9 Test: p=0. 0078 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Category: Peripheral T-cell Lymphoma-NOS by Ki 67+ cells 1. 0 0. 9 Test: p<0. 001 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time Ki 67+ cells (%) CENSOR FAIL TOTAL MEDIAN <=25% 25 27 52 5. 26 26 -75% 35 68 103 1. 89 >75% 12 44 56 1. 36
Overall Survival PTCL-US vs. PTCL-LE 1. 0 0. 9 Test: p=0. 0032 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time Diagnosis PTCL, unspecified PTCL, lymphoepithelioid variant CENSOR FAIL TOTAL MEDIAN 88 204 292 1. 83 18 10 28 17. 2
Clinical Features of PTCL-US and PTCL-LE PTCL-US PTCL-LE 18% 23% 2 35% 38% 3 -5 37% 39% 7% 0% 0. 38 Platelets <150 K 24% 29% 0. 62 Transformed cells >70% 33% 6% 0. 03 IPI 0/1 Mass >10 cm P= 0. 87
Final Multivariate Analysis of Prognostic Factors in PTCL-NOS Controlling for IPI OS Transformed cells >70% FFS Transformed cells >70% HR 2. 2 1. 6 P= 0. 0002 0. 014 Controlling for PIT OS Mass >10 cm Platelets <150 K Transformed cells >70% FFS Platelets <150 K Transformed cells >70% 2. 1 1. 7 1. 9 1. 7 1. 6 0. 04 0. 002 0. 02
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 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time Diagnosis Angioimmunoblastic T-cell lymphoma Peripheral T-cell lymphoma-NOS CENSOR FAIL TOTAL MEDIAN 87 154 241 2. 26 112 218 330 2. 01
Clinical Prognostic Factors of PTCL-NOS vs. Angioimmunoblastic (AI) PTCL-NOS AI P= IPI scores 3 -5 37% 59% <0. 0001 B symptoms 35% 69% <0. 0001 Hgb <11 g/dl 22% 40% <0. 0001
Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by IPI 1. 0 0. 9 Test: p=0. 096 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by patient age 1. 0 0. 9 Test: p=0. 036 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by performance status 1. 0 0. 9 Test: p=0. 0022 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Sub-group: Angioimmunoblastic T-cell lymphoma by B-symptoms 1. 0 0. 9 Test: p=0. 0046 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Sub-group: Angioimmunoblastic T-cell lymphoma by Platelet Count 1. 0 0. 9 Test: p=0. 017 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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 <150 K/cmm 19 41 60 1. 03 >=150 K/cmm 52 90 142 2. 4
Overall Survival Disease Category: Angioimmunoblastic by Transformed T-cell counts 1. 0 0. 9 Test: p=0. 14 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by UNMC-IPI 2 1. 0 0. 9 Test: p<0. 001 Proportion 0. 8 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Time UNMC-PI 2: Age / Perf. Stat / Plt Ct<150 k CENSOR FAIL TOTAL MEDIAN 0 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
Overall Survival Disease Sub-group: Anaplastic large cell lymphoma, ALK+ by IPI 1. 0 0. 9 0. 8 Test: p<0. 001 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Overall Survival Disease Sub-group: Anaplastic large cell lymphoma, ALK+ by Hemoglobin 1. 0 0. 9 Test: p=0. 043 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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 .
Overall Survival Disease Sub-group: Anaplastic large cell lymphoma, ALKby IPI 1. 0 0. 9 Test: p<0. 001 0. 8 Proportion 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 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
Conclusions l Histologic type is a good predictor of survival l IPI is a good predictor of survival in PTCL-NOS along with % of transformed cells l IPI is a poor predictor of survival in angioimmunoblastic type and better prognostic models are needed l IPI is a good predictor of survival in ALCL, ALK+ (along with Hgb <11 g/dl) and ALCL, ALK-
Conclusions l IPI is useful for stratification of most PTCL patients for risk-adapted therapies l New clinical, pathological and molecular genetic predictors are needed to develop more biologically-relevant prognostic models for the various disease entities
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