Transcript
LYMPHOMES NON HODGKINIENS
François Sestier, MD, PhDAbdelouahed Naslafkih, MD, PhD
AQTV, Montréal, 14 Mai 2009
Programme de médecine d’assurance et expertise en
sciences de la santé,Université de Montréal
www.mae.umontreal.cawww.mae.umontreal.ca
1er manuel• Low grade -diffuse lymphocytic Stage Rating
-nodular lymphocytic I class 3 = pp2yrs,std 7th yr -nodular histiocytic II class 2= pp3yrs,std 8th yr III class 1= pp5yrs,std 11th
yr IV DEC to +100, +cl1
• Intermediate-High grade Stage Rating -diffuse lymphocytic, poorly diff I class 2 -diffuse lymphocytic-histiocytic II class 1 -Burkitt’s lymphoma III +100, + class 1 -Unclassified IV DEC to +200 + class 1
2ième manuel
• Low grade lymphomas: -Stage 1 : PP 3yrs , then +50 and 10$ x 7 yrs 11th yr : +50 -Stage II: PP 3 yrs , then +50 and $15 x 7 yrs 11th yr : + 50 -Other stages : PP 10 yrs, then 15$ x 5yrs 16th yr : std
Les LNH sont-ils des risques standards s’ils
survivent 7 à 16 ans ??
OBJECTIFS
• Identifier la littérature médicale la plus récente concernant la mortalité des LNH
• Calculer la mortalité observée en utilisant une méthodologie actuarielle
LNH: définition et épidémiologie
1. Definition: malignant disease of the lymphoid system, highly heterogeneous, both histologically and clinically, with several classifications
2. Epidemiology:- annual incidence: 5-10 new cases per 100 000 persons,- age distribution: middle-age patients and the elderly,- males are affected more often than females (1.5:1.0).
Incidence selon l’âge au diagnostic Source : SEER-Cancer statistics Review 1995-2004
Increasing incidence with age. Differences between SEER registries 2002-2004 and 1975-1977.
Non-Hodgkin lymphoma classification
Histologic classification of non-Hodgkin’s lymphomas - Working
Formulation (WF)
1. Low grade2. Intermediate grade
3. High grade
Histologic classification of non-Hodgkin’s lymphomas - Working
Formulation (WF)
Low grade
A - Small lymphocytic cell.B - Follicular, predominantly small cleaved
cellC - Follicular mixed, small cleaved and large
cell.
Histologic classification of non-Hodgkin’s lymphomas - Working
Formulation (WF)
Intermediate grade
D - Follicular, predominantly large cell.E - Diffuse small cleaved cell.F - Diffuse mixed, small and large cell.G - Diffuse large cell.
Histologic classification of non-Hodgkin’s lymphomas - Working
Formulation (WF)
High grade
H -Large cell immunoblastic.I -Lymphoblastic.J -Small noncleaved cell:
Burkitt’s
Staging: Ann Arbor
I. 1 lymph node region or structureII. >1 lymph node region or structure,
same side of diaphragmIII. Both sides of diaphragmIV. Extranodal sites beyond “E”
designation
subscripts: A, B, E, S
Stages
ANN ARBOR
Stages
SEER
I One group of lymph nodes affected. Localized
II
Two or more teritories affected,
located at one side of the
diaphragm.
Regional
III On both sides of the diaphragm.
DistantIV
Spread beyond the lymph nodes,
(to other organs: bone marrow, liver
or lungs).
ANN ARBOR and SEER classifications
Fever (at least 38°C during 15 days without infection), night sweats or weight lost at least 10 % during the previous 6 months are indicated by the suffix letter A or B.Source : http://www.rapidesregional.com/CPM/CancerAnnualReport2002.htm
Source: NCDB, Commission on Cancer, AcoS. Benchmark Reports v1.1 - November 1, 2002.Rapid City Regional Hospital Cancer Registry.
Source: NCDB, Commission on Cancer, AcoS. Benchmark Reports v1.1 - November 1, 2002.Rapid City Regional Hospital Cancer Registry.
Source: NCDB, Commission on Cancer, AcoS. Benchmark Reports v1.1 - November 1, 2002.Rapid City Regional Hospital Cancer Registry.
Follicular lymphoma and long term survival
Gandhi, Blood Rewiews,2005,19:165-178
IPIInternational prognostic Index
FLIPIFollicular Lymphoma International prognostic index
Risk factors
Age > 60 years
Spread beyond lymph nodes ≥ 2 sites
High serum LDH
Stages III and IV
Performance status (ECOG PS) ≥ 2
Risk factors
Age > 60 ans
Lymph nodes ≥4 sites affected
High serum LDH
Stages III et IV
Hemoglobine < 12 g/dl
Risk class
Low : 0 or 1
Intermediate : 2
High : 3 - 5
Risk class
Low : 0 or 1
Intermediate : 2
High : ≥ 3
Prognostic Index
Adapted from: Perea et al. Prognostic indexes in follicular lymphoma: a comparison of different prognostic systems. Ann Oncol 2005; 16:1508-1513
The International Non-Hodgkin's
Lymphoma Prognostic Factors Project NEJM 1993;329:987-994
A Predictive Model for Aggressive Non-Hodgkin's Lymphoma
USA, Europe, Canada, 1982-19873273 patients (1274 60 years)
NEJM 1993;329:987-994
Factors Independently Prognostic of Overall Survival
Dave, S. S. et al. N Engl J Med 2004;351:2159-2169
Development of a Molecular Predictor of Survival in Follicular Lymphoma
LYMPHOMA SURVIVAL: a textbook approach
Southwest Oncology Group lymphoma survival
LNH
• Surviennent chez le jeune adulte et la personne agée
• Il faut dond tenir compte de l’âge dans le calcul de la mortalité
Age at
diagnosis
Mortality ratio (MR%)
2 years 5 years 10 years
<45 years 5600 5500 2000
45-54 years 1800 1200 750
55-64 years 800 600 400
65-74 years 475 350 225
≥75 years 400 275 200
NHL: Mortality ratio by age groups, SEER 9 Registries for 1988-2003
Stage Survival % MR (%)
Relative Expected
Localized 68.8 85.4 325
Regional 61.7 - 386
Distant 44.9 - 560
All stages 56.3 - 438
LNH: MR at 5 years by stages SEER data (1988-2001)
YearsMR (%)
Men Women Both
0 - 1680 660 670
0 - 2680 600 630
0 - 3555 515 545
0 - 4485 448 475
0 - 5430 400 420
0 - 6385 360 376
0 - 7350 229 343
0 - 8318 300 310
0 - 9290 275 285
0 -10265 255 260
NHL: Mortality ratio by follow-up period SEER 9 Registries , 1988-2003
Netherlands, 1981-891164 patients, age : 64 yrs, 50% women
Overall survival (%)
MR
5 yrs 10 yrs 5 yrs 10 yrs
Nodal (n = 635) 41 23 713% 397%
Extra nodal (n = 389)
41 24 713% 386%
Extensive (n = 140)
29 12 956% 555%
Kroll et al. Ann Oncol 2003;14:131-139CCCW-NHL Registry
Mortality ratio (MR %)
2 years 5 years 10 years 15 years
All 761 475 375 400
Follicular 445 445 425 578
DLCB 995 520 365 430
NHL: Mortality ratio (MR) at 2, 5, 10, and 15 years
Adapted from: Krol et al. Leukemia&Lymphoma 2003
DLCB: diffuse large B-cell lymphomas
CCCW (The Comprehensive Cancer Center West) 1168 patients diagnosed with NHL between1981 and 1989. Median age at diagnosis: 66 years, 49% males , Follow-up 15 years
Survival of patients with NHL vs. Dutch population
Source: Krol et al. Leukemia&Lymphoma 2003
NHL-DLCB
Mortality ratio (MR %)
2
yrs5 yrs 10 yrs
15
yrs
995 520 365 430
470 patients with diffuse large B cells lymphomas , 49% males, median age: 66 years
From: Krol et al. Leukemia & Lymphoma 2003; 44(3):451-458.
After 15 years all patients died
NHL-DiffuseThe Comprehensive Cancer Center West, 1981-89
CCCW-NHL Registry
Netherlands, 1981-89
1167 Patients, age : 64 yrs, 50% women
Follow-up: 8 years
Indolent and agressive NHL
Maartense et al. Cancer 2000; 89(12):2667-2676
CCCW-NHL Registry. Maartense et al. Cancer 2000; 89(12):2667-2676
Effect of age
Type Age at diagnosis (years)
<60 60-64 65 -69 70 -74 ≥75
Indolent
MR : 5 yrs 1290 395 338 525 170
MR : 8 yrs 1360 434 400 360 300
Agressive
MR : 5 yrs 2360 900 745 540 317
MR : 8 yrs 1360 690 550 360 395
NHL: MR at 5 and 8 years by type and age
Adapted from : Maartense et al. Cancer 2000; 89 :2667-2676
CCCW-NHL Registry. Maartense et al. Cancer 2000; 89(12):2667-2676
Effect of age on MR
Age groupMortality Ratios
Indolent DLBL
<60 yrs 1150% 1360%
60 – 64 yrs 450% 695%
65 – 69 yrs 410% 560%
70 – 74 yrs 330% 350%
75 yrs 200% 265%
Maartense et al. Cancer 2000; 89(12):2667-2676
Age groupMortality Ratios
Indolent DLBL
<60 yrs 1150% 1360%
60 – 64 yrs 450% 695%
65 – 69 yrs 410% 560%
70 – 74 yrs 330% 350%
75 yrs 200% 265%
Localized aggressive lymphoma
Rey et al. NEJM 2005;352:1197
France, 1993-2000647 patients (318 ACVBP, 329 CHOP+RX)Age : 46 years, 60% men
Stage I : 66%Stage II : 32%Stage IV : 2%95% IPI score= 0
Follow-up : 8 yearsDeaths = 115
Mortality Ratio* = 560%
Côte d'Or registry,France,
451 patients diagnosed with NHL between
1980-92
Variables MR%
GenderMen 300
Women 200
Age20 – 64 years 980
≥65 years 250
Grade
Low 185Intermediate 280High 515Unknown 475
Period of
diagnosis
1980-1983 263
1984-1987 400
1988-1991 275
NHL: Mortality ratio (MR) at 5 years by different variables
Source : Rolland-Portal et al. Int J Epidemiol 1997; 26 :945-952
Relative survival Mortality
ratio
5 yrs 10 yrs 5 yrs 10 yrs
Low grade 80 74 280 193
Interm. and high grade 52 41 605 368
All grades 60 49 500 316
NHL: MR at 5 and 10 years by grade(Register Côte d’Or)
Follicular lymphomaMontoto et al. Ann Oncol 2002;13:523-530
Spain, 1977-1997201 patients, 53% menAge : 54 yearsStage I: 10%, II: 9%, III: 15%, IV: 66%Overall survival : 71% at 5 years, 48% at 10 years
MR* = 973% at 5 years = 785% at 10 years
*Life table Spain, Total population 1980-89
Montoto, S. et al. Ann Oncol 2002 13:523-530
Time to treatment failure (TTF) and overall survival (OS) in 201 patients with follicular
lymphoma
MR = 785% (10yrs)
Survival of 389 follicular lymphomas : std at 10
yrs????
Diffuse large B-cell lymphoma
( aggressive lymphomas)US,1987-1998128 Patients, (46% men)Age : 65 years5-year overall survival: 43%
Mortality Ratio* = 722%
Colomo et al. Blood 2003:101:78-84
Indolent lymphomaFollicular vs. Non Follicular lymphoma
Corradini et al. J Clin Oncol 2004;22:1460-1468
Italy,1990-9970 patients,60% menAge: 47 years87% stage IVOverall survival at 12 yrs
Follicular subtype: 76%, MR = 514%Non-Follicular : 49%, MR = 1311%
Relapsed Follicular LymphomaAutologous Bone Marrow Transplantation
Freedman et al. Blood 1999;94:3325-3333
USA, 1985-1995153 Patients, 53% menAge: 43 years(66%: stage IV, 24% stage III, 7% stage II, 3% stage
I)
Survival : 69% at 12 years
MR* = 1330%
*Life table US 1989-92
Freedman, A. S. et al. Blood 1999;94:3325-3333
20 yrs survival after ABMT from diagnosis for 153 patients with indolent follicular
lymphoma.
MR* = 1330%
Freedman, A. S. et al. Blood 1999;94:3325-3333
20 yrs survival after ABMT from diagnosis for 153 patients with indolent follicular
lymphoma.
MR* = 1330%,Not std!!
Low grade NHL: Follicular Lymphomaby age, stage and histologic type
MR at 5, 10, and 15 years
Age Age <60 years Age ≥60 years
Follow-up 5 yrs10yr
s
15yr
s
5yr
s
10yr
s
15yr
s
Localized/regional
FSC, FM1983-89 325 275 200 420 310 245
1990-99 307 277 480 355
FLC1983-89 415 232 200 578 361 220
1990-99 475 300 570 385
Distant stage
FSC, FM1983-89 560 465 287 700 455 300
1990-99 550 385 725 460
FLC1983-89 1020 560 287 865 545 345
1990-99 717 370 965 500
FSC: small cleaved-cell follicular lymphoma; FM: mixed follicular lymphoma; FLC: large-cell follicular lymphoma
Adapted from: Swenson et al. J Clin Oncol 2005; 23:5019-5026, ref. 12
Localized Intermediate and high-grade Non-hodgkin's lymphoma
Soutwest Oncology Group, 1988-1995442 patients (CHOP: 201; CHOP+RX :200)Age : 59 years5-year overall survival : CHOP : 72%CHOP+RX : 82%
Miller et al. NEJM 1998;339:21-26
Miller et al. NEJM 1998;339:21-26
5-year overall survivalCHOP+RX : 82%CHOP : 72%
MR* = 396% CHOP+RX
MR* = 648% CHOP
*Life table US,1989-91
Miller et al. NEJM 1998;339:21-26
MR = 396%MR = 675%MR = 1390%
*Life table US,1989-91
Intermediate or high-grade Non-Hodgkin lymphoma
Italy, 1984-1998186 patients, 52% menAge: 56 years
Overall survival : 60.4% at 10 yearsMortality ratio = 495%
Rossini et al. Cancer 2004;100:350-355
Intermediate or high-grade Non-Hodgkin lymphoma
MR by stage Stage I-II = 431%Stage III-IV = 995%
MR by IPIIPI 1 = 260%IPI 2 = 495%IPI 3 = 800% IPI 4 = 1170%
Rossini et al. Cancer 2004;100:350-355
NHL mortality: Relative risk by IFLP(Follicular Lymphoma International Prognostic Index)
Adapted from: Solal-Céligny et al. Blood 2004; 104 :1258-1265
Group Prognostic
factorsRR
Low risk 0 - 1 1.0
Intermediate
risk 2 2.3
High risk ≥ 3 4.3
High grade NHL
3273 patients aggressive NHL (High/interm grades), Age at diagnosis: 65 years, Follow-up: 5 years
MR%
All 420Male 420Female 410 Age ≤60 years 655 Age >60 years 355
Stages
I 158II 275III 425IV 577I/II 245III/IV 525
International Non-Hodgkin's Lymphoma Prognostic Factors Project 1982-98Mortality Ratio according to Life Table US, 1985-1989)
Adapted from: NEJM 1993
IPI MR (%)
2 years 5 yearsAll patients
Low 0 ou 1 275 210
Low-
Intermediaite
2 613 435
High-
Intermediaite
3 866 535
High 4 ou 5 1360 815
Age ≤60 yrs
Low 0 325 245
Low-
Intermediaite
1 708 480
High-
Intermediaite
2 1475 965
High 3 2500 1365
Age >60 yrs
Low 0 225 240
Low-
Intermediaite
1 375 330
High-
Intermediaite
2 655 395
High 3 945 585
NHL: Mortality ratio at 2 and 5years by IPI
Adapted from: The International NHL Prognostic Factors Project. NEJM 1993
FU: 5 yrs ACVBP CHOP Total
MR% 645 785 715
GELA study 18 France, 1993-1998708 patients aggressive lymphoma (stages III / IV); 80% diffuse large B-cellMedian age at diagnosis : 65 years ; 56% males2 treatment groups (ACVBP and CHOP).Median follow-up period was 68 months. Survival at 5 years was 46% and 38% respectively Expected survival from Life table France, 1995-99.
NHL stages III-IV: Mortality by therapeutic modalities
The International Lymphoma Study Group Classification of Non-Hodgkin’s
Lymphoma1403 cases (untreated) from 8 countries,
1988-90Omaha, NE: 200
Vancouver, Canada: 202Cape Town, South Africa: 196London, UK: 120Locarno, Switzerland: 80Lyon, France: 195Wurzburg, Germany: 210Hong Kong: 200
Blood 1997;89:3909-3918
Consensus diagnosisAge
(Years)Male(%)
5-year survival %
Index0/1
Index 4/5
Follicular, all grades 59 42 84 17
Mantle cell 63 74 57 0
Marginal zone B-cell, MALT 61 45 89 40
Marginal zone B-cell, nodal 58 41 76 50
Small lymphocytic (CLL) 65 53 76 38
Diffuse large B-cell 64 55 73 22
Primary mediastinal large B-cell
37 34 77 0
High-grade B-cell, Burkitt-like
55 59 71 0
Precurssor T-lymphoblastic 25 74 29 40
Peripheral T-cell, all types 61 56 36 15
Anaplastic large T/null cell 33 69 81 83
NHL Classification ProjectSurvival by histologic type and the International Prognostic Index
Blood 1997;89:3909-3918
Consensus diagnosisMR
Index 0/1 Index 4/5
Follicular, all grades 330% 2900%Mantle cell 587% ----Marginal zone B-cell, MALT 185% 1330%Marginal zone B-cell, nodal 545% 1320%Small lymphocytic (CLL) 280% 925%Diffuse large B-cell 306% 1312%Primary mediastinal large B-cell 3393% ----High-grade B-cell, Burkitt-like 2850% ----Precurssor T-lymphoblastic 24366% 18600%Peripheral T-cell, all types 1368% 2338%Anaplastic large T/null cell 3170% 2665%
NHL Classification ProjectBlood 1997;89:3909-3918
Mortality Ratio ( life table Canada 1990-92)
Type of lymphomas
Age (Yrs)
Survival5 yrs
Exp. survivalLife table US, 1998
MR
B cell Lymphocytic 65 51% 88% 500%
Mantel cell 63 27% 90% 1100%
Extranodal marginal Zone B (MALT)
60 74% 92% 350%
Follicular 59 72% 93% 450%
Diffuse large B Cell lymphoma
64 46% 89% 625%
Burkit’s lymphoma 31 45% 99% 7350%
Precursor T Cell lymphoblastic
28 26% 99% 11805%
Anaplastic Large T / Null cell
34 77% 99% 2500%
Peripheral T cell NHL 61 25% 93% 1600%
Common types of lymphoma and 5-year survival
Adapted From: Harrison’s Principles of Internal Medicine, 16th ed. 2005
B-cell Neoplasms Age P P’ MR
Small lymphocytic/B cell L ymphocytic leukemia
65 51% 88% 500%
Lymphoblastic lymphoma
Follicular (grade I and II) 59 72% 93% 450%
Marginal zone B- cell lymphoma 60 74% 92% 350%
Mantle cell lymphoma 63 27% 90% 1100%
The indolent lymphomasAdapted from Up To Date (source: J Clin Oncol 1997;17:3835)
P = Observed survival at 5 yrs
P’= Expected survival (life table US 1989)
Lymphomes indolents
• Sont incurables• Invasion moelle osseuse• Rémission spontanée dans 25 % des cas• Rechutes 2-3 après et ensuite de plus en plus
rapidement• Sur-mortalité persist e après 10 ans• Certains LNH chez les personnes agées peuvent
être assurés avec surprime (?)• Les LNH indolents doivent être refusés
Tel: 1-877-343-7606Tel: 1-877-343-7606Fax : 1-514-343-7074Fax : 1-514-343-7074
E-mail: E-mail: françois.sestier@umontreal.cafrançois.sestier@umontreal.ca
top related