Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
André Bosly, M.D., Ph.D.Université de Louvain
Mont-Godinne, Belgique
ESH Tunis, le 29 octobre 2010
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Données épidémiologiques
Mortalité par cancer par an (nx 1000) en Europe
Age-standardized incidence rates (ASR) of NHL worldwide
0
2
4
6
8
10
12
14
16
EasternAsia
SouthernAfrica
WesternEurope
Australia NorthernAmerica
AS
R p
er10
0,00
0 w
orl
dw
ide
Males
Females
Müllier A et al, Ann Hematol 2005; 84 : 1-12
SEER 1975–2000 age-adjusted incidence rates of NHL by gender
Fischer SG et al, Oncogene 2004; 23:6524-6534
Frequency of subtypes of lymphomas
Non-Hodgkin's lymphomas. Coiffier, p. 7
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Facteurs pronostiques cliniques : l’IPI
Smith A. Br J Haematol 2010; 148:739-753
International prognostic index
Survival according to IPI score6696 patients included in GELA randomized studies
Overall survival Progression-free survival
Revised IPI in the rituximab era
Risk groupNo of
IPI factors
Patients,%
4-year PFS, %
4-year OS, %
Standard IPI
Low 0–1 28 85 82
Low–intermed 2 27 80 81
High–intermed 3 21 57 49
High 4–5 24 51 49
Revised IPI
Very good 0 10 94 94
Good 1–2 45 80 79
Poor 3–5 45 53 55Sehn LH et al, Blood 2007; 109:1857–1861
Sehn et al, Blood 2007; 109 : 1857-61
RIPI
4-year PFS
4-year OS
Comparaison de 4 IPI
Advani RH et al, BHJ 2010; 151 : 143-151
Ziepert M., J Clin Oncol 2010; 28:2373-2380
Validity of IPI in the rituximab era (german group)
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Facteurs biologiques :données de micro-array : au moins deux maladies
Gene expression arrays
Subclassification of diffuse large B-
celllymphoma
Alizadeh et al,Nature 2000
Clinical study according to phenotype of diffuse large cells lymphomas
(Alizadeh, 2000)
Subgroups of diffuse large B-cell lymphoma
defined by gene expression profiling
274 DLBCL Biopsy Samples
Diffuse Large B-cell Lymphoma :at least two diseases
Germinal centerB cell-like (GCB)
ActivatedB cell-like (ABC)
Cell of Origin
OncogenicMechanism
s
Clinical Outcom
e
Germinal centerB cell
? Post-Germinal Center B cell
- t(14;18) translocation of
BCL-2- Chr. 2p
amplification of c-rel locus
Constitutive activationof NF-kB
Favorable60% 5-yr survival
Poor35% 5-yr survival
GCB and ABC in R-CHOP treated patients
Lenz et al, NEJM 2008; 359 (22) : 2313-23
Hartmann & Rosenwald, EHA educational program 2009
Predictor score in R-CHOP treated patients
N Engl J MED. G. Lenz et al. 2008; 359 (22): 2313-23
Stromal 1
N Engl J MED. G. Lenz et al. 2008; 359 (22): 2313-23
Stromal 2
N Engl J MED. G. Lenz et al. 2008; 359 (22): 2313-23
Survival model in R-CHOP treated patients
N Engl J MED. G. Lenz et al. 2008; Suppl. to 359 (22): 2313-23
Survival model and IPI
N Engl J MED. G. Lenz et al. 2008; Suppl. to 359 (22): 2313-23
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Facteurs biologiques :expression de gènes en
immunohistologie
Ott G et al, Blood 2010-03-276766
Ricover study : Hans algorithm
Ott G et al, Blood 2010-03-276766
RICOVER study : Hans algorithm
All patients :
EFS, R-CHOP patients (52 patients)
Ott et al, Blood 2010
Ott G et al, Blood 2010-03-276766
RICOVER study histology
Ott G et al, Blood 2010-03-276766
RICOVER study histology
Nyman H et al, Modern Pathology 2009; 22 : 1094-1101
Hansalgorithm
Murisalgorithm
Nymanalgorithm
Nyman H et al, Modern Pathology 2009; 22 : 1094-1101
Nyman
Muris
Hans
de Jong D et al, J Clin Pathol 2009; 62 : 128-138
CV1=2; CV2=1 CV1=26; CV2=4
CV1=20; CV2=11 CV1=15; CV2=16
Lunenburg consortium
CV1=31; CV2=21 CV1=23; CV2=20
CV1=21; CV2=11 CV1=27; CV2=21
de Jong D et al, J Clin Pathol 2009; 62 : 128-138
Lunenburg consortium
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Réarrangements de MYC et survie
Smith SM et al, Blood Cells Mol Diseases 2010
Univariate Kaplan-Meier analysis of overall survival in the MYC rearrangement (MYC-R)versus nonrearranged patients. Patients with rearrangement of MYC have a significantly inferior outcome compared to those without (hazard ratio, 2.03; 95 % CI, 1.15 to 3.58). The probability of survival at 2 years was 0.35 in the MYC rearrangement group versus0.61 for all others, based on n=240 patients with MYC data and clinical follow-up.
Barrans S et al., J Clin Oncol 2010; 28:3360-3365
Réarrangement de c-myc et DLBCL
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Dose-intensité de chimiothérapie et survie
Bosly, Bron et al, Ann Hematol 2008
Effect of dose-intensity on survival
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
TEP et évaluation de la réponse précoce
TP 15112007
PET CT for staging
2-year outcome
Study n PET after . . . PET- PET+
Jerusalem 2000 28 Median : 3 cycles 62% (PFS) 0% (PFS)
Spaepen 2002 70 Median : 3 cycles 85% (PFS) 4% (PFS)
Kostakoglu 2002 30 1 cycle 85% (PFS) <15% (PFS)
Haioun 2005 90 2 cycles 82% (EFS) 43% (EFS)
Mickaeel 2005 121 Median : 2 cycles 87% (PFS) 34% (PFS)
Early treatment evaluation
Before treatment At 2 cycles At 4 cycles
FDG-PET2 (+)
Early treatment evaluation
Event-free survival and overall survival according
to response at 2 cycles on the basis of PET (n = 90)
PET– (n=54)
PET+ (n=36)
Pro
bab
ilit
y o
f E
FS
p<0.0001
Years after randomisation
Event-free survival
p=0.006
Median follow-up: 2 years
Overall survival
100
80
60
40
20
0
100
80
60
40
20
00 1 2 3 0 1 2 3
Years after randomisation
Pro
bab
ilit
y o
f O
S
Haioun C, et al, Blood 2005
Receiver operating characteristic (ROC) plotting for (A) advanced-stage Hodgkin's lymphoma and (B) diffuse large B-cell lymphoma. Individual study estimates of sensitivity and 1 − specificity are shown (open circles). Summary ROC curve is presented only for DLBCL. Closed square represents the summary estimates. Dashed boundary represents the 95% confidence region for the summary sensitivity and specificity.
Terasawa T et al, J Clin Oncol 2009; 27 : 1906-1914
Specificity and sensitivity of PET are not so good in DLBCL in comparison with HD
Interim PET NHL (4 cycles)False positive PET scans – PPV 26%
Moskowitz et al, J Clin Oncol 28: 1896, 2010
False positive PET results
Visual assessment : normal
Interval : 10 – 14 days
G-CSF
SUV = 1.4
Gallamini, A. et al. J Clin Oncol; 25:3746-3752 2007
Interim PET in ABVD-treated HL patients
SUV = 3.5
Visual vs. quantitative analysis2 cycles, n=92
5.0
> 5.0
P = .002
Quantitative analysis(SUVmax at 2 cycles)
Visual analysis(Créteil, MRU)
Quantitative analysis(% reduction SUVmax)
Lin, Itti et al. J Nucl Med 2007;48:1626-32
Reduction of 14/17 false positives Cut-off may vary with histology, treatment, PET center
PET2 (-)
PET2 (+)
P =.009
Pro
bab
ility
of
EF
S
Months after inclusion Months after inclusion Months after inclusion
P < .0001
> 65.7%
65.7%
Visual analysis(Juweid, IHP)
Visual analysis(Créteil, MRU)
Quantitative analysis(% reduction SUVmax)
P < .0001 P < .0001P < .0001
PET4 (-)
PET4 (+)
> 72.9%
72.9%
PET4 (-)
PET4 (+)Pro
bab
ility
of
EF
S
Months after inclusion Months after inclusion Months after inclusion
Reduction of false positives if we wait for 4 cycles Juweid criteria acceptable, Créteil slightly better Visual analysis reliable, SUV more objective
Itti et al. J Nucl Med 2009;50:527-33
Visual vs. quantitative analysis4 cycles, n=80
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Traitement des formes localisées
ACVBP compared with CHOP plus radiotherapy :
the LNH93-1 study
R
0 2 84
0 3 6 10
2210 12 14 16
weeks
weeks
ACVBP ACVBPACVBP
CHOP CHOP CHOP
Methotrexate3g/sqm
+ rescue
Ifosfamide1500 mg/sqm
Etoposide300 mg/sqm
Cytarabine100mg/sqm x4
Induction ConsolidationACVBP
Doxorubicin : 75 mg/sqm D1Cyclophosphamide : 1200 mg/sqm D1Vindesine : 2 mg/sqm D1, D5Bleomycin : 10 mg D1, D5Prednisone : 60 mg/sqm D1-5
CHOP
Doxorubicin : 50 mg/sqm D1Cyclophosphamide : 750 mg/sqm D1Vincristine : 1,4 mg/sqm D1Prednisone : 40 mg/sqm D1-5
involved field
radiotherapy, 40 Gy
(5 x 1,8 Gy / week)
18 20
ACVBP
CHOP plus radiotherapy
pro
ba
bil
ity
of
Ov
era
ll S
urv
iva
l
P = 0.001
No. at risk
ACVBP 318 307 296 286 271 236 206 163 126 80 34
CHOP plus 329 314 292 280 265 231 199 152 113 70 28radiotherapy
m f-up : 7.7 y
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11
years after randomization
The LNH93-1 study : overall survival
Reyes F. et al, 2005 - NEJM
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years after Randomization
CHOP
CHOP plus radiotherapyP
roba
bilit
y
P = 0.5
No. at risk
CHOP 277 220 202 179 157 130 112 87 66 39
19 1
CHOP plus 299 249 226 193 170 143 112 90 64 48
30 9radiotherapy
93-4 study : Event Free Survival
n = 277
n = 299
med f-up= 7y
La radiothérapie n’a pas de place en première ligne
Bonnet C, Fillet G, JCO 2007
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Years after Randomization
Pro
bab
ilit
y
P = 0.5
No. at risk
CHOP 277 249 226 206 178 153 131 102 75 45
22 1
CHOP plus 299 265 243 211 187 155 123 98 68 50
30 9radiotherapy
93-4 study : Overall Survival
CHOP n=277
CHOP plus radiotherapy n=299
med f-up= 7y
La radiothérapie n’a pas de place en première ligne
Bonnet C, Fillet G, JCO 2007
Lymphoma-associated deaths:Chemo: 42R-Chemo : 13
0 5 10 15 20 25 30 35 40 45 50Months
Pro
bab
ilit
y
R-Chemo
Chemo
95%
86%
MInT : overall survival
Pfreundschuh M, et al. Blood 2004; 104:40a (Abstract 157)
P = 0.0002
Median observation time : 23 months
1.0
0.8
0.6
0.4
0.2
0
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Traitement des formes avancées chez le sujet agé
DLBCL Age 60–80 years No prior treatment PS 0–2 Stage II–IV
RANDOMIZATION
LNH 98.5 study : Design
CHOP q3wk x 8
Rituximab+
CHOPq3wk x 8
Coiffier B et al, N Engl J Med 2002;346:235
Rituximab: 375 mg/m2 on day 1Cyclophosphamide: 750 mg/m2 on day 1Doxorubicin: 50 mg/m2 on day 1Vincristine: 1.4 mg/m2 (up to 2 mg) on day 1Prednisolone: 40 mg/m2/d days 1–5
Rituximab: 375 mg/m2 on day 1Cyclophosphamide: 750 mg/m2 on day 1Doxorubicin: 50 mg/m2 on day 1Vincristine: 1.4 mg/m2 (up to 2 mg) on day 1Prednisolone: 40 mg/m2/d days 1–5
LNH-98.5 : Improved responserate and quality of response with R-
CHOP
63
6
ORR = 69 %(n = 197)
76
7
Pat
ien
ts (
%)
80
60
40
20
0
100
CHOPR-CHOP
Non-evaluable / otherDeath during treatmentProgressive diseasePartial responseComplete response / CRu
ORR = 83 %(n = 202)
Coiffier B et al, New Engl J Med 2002;346:235–242
9
6 6
22
R-CHOP vs CHOPp = 0.005
2 3
p = 0.005
Gela (french and belgian study)in aggressive lymphoma
OS – Median follow-up 7 y.
Coiffier, ASCO 2007
Overall survival according to age
60-69 years 75-80 years70-74 years
60-69 70-74 75-80
CHOP 40 41 21
R-CHOP 58 55 417-year OS (%)
Coiffier, B. et al. Blood 2010;116:2040-2045
Overall survival in patients treated with CHOP and R-CHOP(10 years FU)
N Chemo Response (%)Rituximab benefit
EFS or PFS OS
GELA1 399Elderly (60–80)
CHOP-21 x 876 vs 63
p = 0.0050.00002 0.0073
RICOVER-602 1222Elderly (61–80)
CHOP-14 x 6
CHOP-14 x 8
78 vs 68
76 vs 72< 0.001 0.003*
HOVON/NORDIC3 199 Elderly (65–80)
CHOP-14 x 8 ND < 0.01 0.05
Intergroup USA4†
(Habermann)632
Elderly (> 60)CHOP-21 77 vs 76 0.003 0.05
MInT5
824Young (18–60)
Low risk
CHOP-21or others
86 vs 68
p < 0.0001< 0.0001 0.0001
British Columbia6 292All ages
CHOP-like ND 0.002 < 0.0001
Czech Republic7 376Young
CHOP-like ND 0.0001 0.0007
1. Feugier P, et al. JCO 2005; 23:4117–4126; 2. Pfreundschuh M, et al. Blood 2006; Abstract 205;3. Sonneveld P, et al. J Blood 2006; 108:Abstract 210; 4. Habermann TM, et al. JCO 2006; 24:3121–3127;
5. Pfreundschuh M, et al. Lancet Oncol 2006; 7:379–391; 6. Sehn LH, et al. JCO 2005; 23:5027–5033;7. Trnĕný M, et al. Blood 2005; 106:Abstract 2444
* p-values for R-CHOP-14 x 6† Secondary analysis without maintenance
Improved EFS and OS with R-CHOP is consistent
in clinical trials and clinical practice
RICOVER-60 : Improved TTF with8 x rituximab + 6/8 x CHOP-14
R-CHOP-14 vs CHOP-14
Time (months)
Pro
bab
ilit
y
6 cycles vs 8 cycles
8 x (R)-CHOP-14(n = 415)
6 x (R)-CHOP-14(n = 413)
Time (months)
Pro
bab
ilit
y
05 10 15 200 30
0.2
0.4
0.6
0.8
1.0
450
5 10 15 20 35
0.2
0.4
0.6
0.8
1.0
45035 4025 25 30 40
p = 0.23
8 x rituximab+ 6/8 x CHOP-14(n = 414)
6/8 x CHOP-14(n = 414)
p = 0.000025 α-crit* = 0.031
Pfreundschuh M et al, Blood 2006;108:Abstract 205* R-CHOP-14 vs CHOP-14
LNH 03-6B : Study Design
Filgrastim or Pegfilgrastim according to physicians’decision
3 months
C5 FU1
R Response
R-CHOP14+ IT MTX
R-CHOP21
Response
C2 C7 C8
C1 C2 C3 C4 C5 C6 C7 C8 FU1FU0
FUn
R-CHOP21 + IT MTX
Response
C1
FUn
FU0
R-CHOP14
C3 C4 C6
3 months
3 months 3 months
Delarue et al Ash2009Delarue et al Ash2009
Distribution of patients
Patients randomizedbefore January 1st, 2006
N = 202
R-CHOP14N = 103
R-CHOP21N = 99
Complete treatment received : N = 73Premature withdrawal : N = 30
Complete treatment received : N = 74No treatment received : N = 1Premature withdrawal : N = 24
Dose-intensity
Is R-CHOP14 given every 14 days ?
R-CHOP14 R-CHOP21
Median interval between two cycles
15 days(9 – 70)
21 days(19 – 63)
Median dose-intensity
R-CHOP14 R-CHOP21
CPM 84 % 96%
DOX 83 % 95 %
18/103 patients in R-CHOP14 group
received R-CHOP ≥ 18
R-CHOP14 R-CHOP21
G-CSF use 90 % 68 %
R-CHOP14 = 125 % of R-CHOP21
Event-free survival
Median EFS : - 22 months (R-CHOP14) vs NR (R-CHOP21)2-year EFS :- 48% (R-CHOP14) vs 61% (R-CHOP21)
Overall survival
-2-year OS:- 67% (R-CHOP14) vs 70% (R-CHOP21)
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Traitement des sujets jeunes de mauvais pronostic
The ACVBP regimen – a dose-intense chemotherapy regimen
LNH93-1: young, good prognosis
Reyes F et al. NEJM 2005
ACVBP
CHOPP = 0.03
0
20
40
60
80
100
0 2 4 6 8
Years
% survival
Tilly H et al. Blood 2003
LNH93-5: 60–70 y, poor prognosis
0
20
40
60
80
100
0 2 4 6 8
Years
% survival
1 3 5 7 9
P = 0.03
ACVBP
CHOP
Doxorubicin 75 mg/m² d1Cyclophosphamide 1200 mg/m² d1Vindesine 2 mg/m² d1, d5Bleomycin 10 mg d1, d5Prednison 60 mg/m² d1 to d5MTX intra-thecal 15 mg d2G-CSF 5 µg/kg d6 to d13
CH, Berlin EHA 2009
LNH 03-2B
• Lymphomes diffus grandes cellules B
• Patients <60 ans IPI=1
• R-ACVBP/R-CHOP
• Voir communication orale:
C.Recher ASH 2010
75%
60%
75%
60%
study N Median Min MaxFollow-up (months) LNH03-3 181 27 0 44Follow-up (months) LNH98-3 181 26 0 47
Matched control study : Progression free survival
PFS
R-ACVBP
ACVBP
CH, Berlin EHA 2009
Survival with ACVB in LNH Regimens
(in randomized studies)
3116 patients
R-ACVBP
R-CyclOBEAP in young patients with high-risk DLBCL
Niitsu N, Int J Hematol 2010; 92 : 231-237
77
EFS
with Rituximab
without Rituximab
6543210
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
p=0.013
Mega-CHOEP with and without Rituximab, Patients with DLBCL: EFS
Time (years)
n=64
n=29
Glass et al: Ann Oncol 2010, Epub doi:10.1093/annonc/mdq235
R
Rituximab (375mg/m²)
CH
OE
P-1
4
CH
OE
P-1
4
CH
OE
P-1
4
CH
OE
P-1
4
CH
OE
P-1
4
CH
OE
P-1
4
CH
OE
P-1
4
1 15 29 43 57 71 85 99
PBSC PBSCPBSC
mCHOEP IICYC 4500ADR 70VCR 2ETO 960PRD 500
43 64221 77 9814 36 56
mCHOEP IIICYC 4500ADR 70VCR 2ETO 960PRD 500
mCHOEP IVCYC 6000ADR 70VCR 2ETO 1480PRD 500
DSHNHL 2002-1 -- R-MegaCHOEPstudy design after amendment 1 for CD20-pos. B-NHL
mCHOEP ICYC 1500ADR 70VCR 2ETO 600PRD 500
CHOEP-14CYC 750ADR 50VCR 2ETO 300PRD 500
PRD and VCR doses are absolute, all others are per m²
days
DSHNHL 2002-1 -- MegaCHOEPProgression-free survival
Months
0 10 20 30 40 50 60 70
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
R-CHOEP-14
R-MegaCHOEP
p=0.119
DSHNHL 2002-1 -- MegaCHOEPOverall survival
0 10 20 30 40 50 60 70
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
p=0.142
R-CHOEP-14
R-MegaCHOEP
Months
Greb A et al, Cancer Treatment Reviews 2007; 33 : 338-346
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Traitement des rechutes
Gisselbrecht C et al, J Clin Oncol 2010; ahead of print, July 26
OS (intent to treat)
Gisselbrecht C et al, J Clin Oncol 2010; ahead of print, July 26
PFS undergoing ASCT (ITT)
PROGRESSION-FREE SURVIVAL ACCORDING TO PRIOR RITUXIMAB
(INDUCTION ITT)
PROGRESSION-FREE SURVIVAL ACCORDING TO FAILURE FROM
DIAGNOSIS (INDUCTION ITT)
N=160
N=22831%
64%N=147
N=24130%
62%
Aggressive B-NHL –CORAL Trial - PFS
Gisselbrecht et al JCO 2010, Epub
Failure from diagnosis > 12 months Failure from diagnosis =< 12 months
N= 106
N= 54
N= 41
N= 187
Aggressive B-NHL –CORAL Trial Response- EFS
Gisselbrecht et al JCO 2010, Epub
8787
Aggressive B-NHL Allogeneic and autologous SCT in aggressive B cell lymphoma
DSHNHLDSHNHL
Pro
bab
ility
of
EF
S
CORAL:HDT + autologous SCT
0 12 24 36 48
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 12 24 36 48 60 72
Time after Transplant (Months)
DSHNHL R3 (B cell lymphoma):HDT + allogeneic SCT
Pro
bab
ility
of
EF
S
No prior rituximab: 54.6 (22,9-78,0)%, n=11
prior rituximab: 34,6 (19,9-49,7)%, n=45
Allogeneic SCT in relapsed DLBCLReduced intensity conditioning : Results
Thomson et al. JCO 2009; 27 (3): 426
OSNRM
RRPFS
sens
ref.
Lymphomes diffus à grandes cellules B
Facteurs pronostiques et traitement
Nouveaux traitements
Briones J, Expert Rev Anticancer Ther 2009; 9 : 1305-1316
Briones J, Expert Rev Anticancer Ther 2009; 9 : 1305-1316
Phase III study testing a maintenance with lenalinomide
REMARC study
Role of new agents in lymphoma
Phase II combination studies in B-cell lymphoma
- Bortezomib with R-CHOP:V-R-CHOP (Mounier N et al. Cancer 2009)
- Dose finding combination of VEGF-Trap with R-CHOP-Phase I (Haioun C. et al,; accrual completed)
- Dose finding combination of Lenalinomide with R-CHOPPhase I (Tilly H. et al, ongoing)
CH, Berlin EHA 2009
Conclusions (1)
• Les lymphomes diffus à grandes cellules sont les LNH les plus fréquents
• L’IPI demeure le facteur pronostique clinique le plus important
• GCB et ABC représentent 2 sous-types de pronostic différent mais une méthode simple et reproductible pour les déterminer reste à définir
• L’évaluation de la réponse par TEP est prédictive de l’évolution à long terme
Conclusions (2)• Les formes localisées sont traitées par rituximab et
chimiothérapie sans irradiation• R-CHOP 21 est le standard de traitement des
formes avancées chez le sujet agé• Un traitement plus intense (R-ACVBP) est
nécessaire dans les formes avancées chez le sujet jeune
• Les traitements intensifs avec autogreffe sont indiqués en cas de rechute
• L’allogreffe avec conditionnement non myélo-ablatif est une option en cas de mauvais pronostic
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