Transcript Diffuse large B cell lymphoma Prognostic factors and treatment

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
ASR per100,000 worldwide
16
14
12
10
Males
Females
8
6
4
2
0
Eastern
Asia
Southern
Africa
Western
Europe
Australia
Northern
America
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
International prognostic index
Smith A. Br J Haematol 2010; 148:739-753
Survival according to IPI score
6696 patients included in GELA randomized studies
Overall survival
Progression-free survival
Revised IPI in the rituximab era
No of
IPI
factors
Patients,
%
4-year
PFS, %
4-year OS,
%
0–1
28
85
82
Low–intermed
2
27
80
81
High–intermed
3
21
57
49
4–5
24
51
49
0
10
94
94
Good
1–2
45
80
79
Poor
3–5
45
53
55
Risk group
Standard IPI
Low
High
Revised IPI
Very good
Sehn LH et al, Blood 2007; 109:1857–1861
RIPI
4-year PFS
4-year OS
Sehn et al, Blood 2007; 109 : 1857-61
Comparaison de 4 IPI
Advani RH et al, BHJ 2010; 151 : 143-151
Validity of IPI in the rituximab era
(german group)
Ziepert M., J Clin Oncol 2010; 28:2373-2380
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-cell
lymphoma
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 center
B cell-like (GCB)
Activated
B cell-like (ABC)
Cell of Origin
Germinal center
B cell
? Post-Germinal
Center B cell
Oncogenic
Mechanisms
- t(14;18) translocation
of BCL-2
- Chr. 2p amplification
of c-rel locus
Constitutive activation
of NF-kB
Clinical
Outcome
Favorable
60% 5-yr survival
Poor
35% 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
Ricover study : Hans algorithm
Ott G et al, Blood 2010-03-276766
RICOVER study : Hans algorithm
All patients :
Ott G et al, Blood 2010-03-276766
EFS, R-CHOP patients (52 patients)
Ott et al, Blood 2010
RICOVER study histology
Ott G et al, Blood 2010-03-276766
RICOVER study histology
Ott G et al, Blood 2010-03-276766
Hans
algorithm
Muris
algorithm
Nyman
algorithm
Nyman H et al, Modern Pathology 2009; 22 : 1094-1101
Nyman
Muris
Hans
Nyman H et al, Modern Pathology 2009; 22 : 1094-1101
Lunenburg consortium
CV1=2; CV2=1
CV1=26; CV2=4
CV1=20; CV2=11
CV1=15; CV2=16
de Jong D et al, J Clin Pathol 2009; 62 : 128-138
Lunenburg consortium
CV1=31; CV2=21
CV1=21; CV2=11
CV1=23; CV2=20
CV1=27; CV2=21
de Jong D et al, J Clin Pathol 2009; 62 : 128-138
Lymphomes diffus
à grandes cellules B
Facteurs pronostiques et traitement
Réarrangements de MYC et survie
Smith SM et al, Blood Cells Mol Diseases 2010
Réarrangement de c-myc et DLBCL
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 versus
0.61 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
Lymphomes diffus
à grandes cellules B
Facteurs pronostiques et traitement
Dose-intensité de chimiothérapie et survie
Effect of dose-intensity on survival
Bosly, Bron et al, Ann Hematol 2008
Lymphomes diffus
à grandes cellules B
Facteurs pronostiques et traitement
TEP et évaluation de la réponse précoce
PET CT for staging
TP 15112007
Early treatment evaluation
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
FDG-PET2 (+)
At 4 cycles
Event-free survival and overall survival according
to response at 2 cycles on the basis of PET
(n = 90)
Event-free survival
Overall survival
100
Probability of OS
Probability of EFS
100
80
PET– (n=54)
60
40
PET+ (n=36)
20
p<0.0001
0
80
60
Median follow-up: 2 years
40
20
p=0.006
0
0
1
2
Years after randomisation
3
0
1
2
3
Years after randomisation
Haioun C, et al, Blood 2005
Specificity and sensitivity of PET
are not so good in DLBCL in comparison with HD
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
Interim PET NHL (4 cycles)
False positive PET scans – PPV 26%
SUV = 1.4
False positive PET results
Visual assessment : normal
Interval : 10 – 14 days
G-CSF
Moskowitz et al, J Clin Oncol 28: 1896, 2010
Interim PET in ABVD-treated HL patients
SUV = 3.5
Gallamini, A. et al. J Clin Oncol; 25:3746-3752 2007
Visual vs. quantitative analysis
2 cycles, n=92
Visual analysis
Probability of EFS
(Créteil, MRU)
Quantitative analysis
Quantitative analysis
(SUVmax at 2 cycles)
(% reduction SUVmax)
 5.0
PET2 (-)
> 65.7%
P < .0001
PET2 (+)
P = .002
P =.009
Months after inclusion
> 5.0
 65.7%
Months after inclusion
Months after inclusion
 Reduction of 14/17 false positives
 Cut-off may vary with histology, treatment, PET center
Lin, Itti et al. J Nucl Med 2007;48:1626-32
Visual vs. quantitative analysis
4 cycles, n=80
Visual analysis
Probability of EFS
(Créteil, MRU)
Visual analysis
Quantitative analysis
(Juweid, IHP)
(% reduction SUVmax)
PET4 (-)
PET4 (-)
P < .0001
P < .0001
PET4 (+)
PET4 (+)
Months after inclusion
Months after inclusion
> 72.9%
P < .0001
 72.9%
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
Lymphomes diffus
à grandes cellules B
Facteurs pronostiques et traitement
Traitement des formes localisées
ACVBP compared with CHOP plus radiotherapy :
the LNH93-1 study
ACVBP
Induction
Doxorubicin : 75 mg/sqm D1
Cyclophosphamide : 1200 mg/sqm D1
Vindesine : 2 mg/sqm D1, D5
Bleomycin : 10 mg D1, D5
Prednisone : 60 mg/sqm D1-5
Consolidation
Ifosfamide
Methotrexate
1500 mg/sqm
Cytarabine
3g/sqm
+ rescue
Etoposide
100mg/sqm x4
300 mg/sqm
ACVBP
ACVBP
ACVBP
0
2
4
8
10
12
14
16
18
20
22
weeks
R
0
CHOP
CHOP
Doxorubicin : 50 mg/sqm D1
Cyclophosphamide : 750 mg/sqm D1
Vincristine : 1,4 mg/sqm D1
Prednisone : 40 mg/sqm D1-5
3
CHOP
6
CHOP
10
involved field
radiotherapy, 40 Gy
(5 x 1,8 Gy / week)
weeks
The LNH93-1 study : overall survival
probability of Overall Survival
100
ACVBP
90
80
70
CHOP plus radiotherapy
60
50
40
30
P = 0.001
20
m f-up : 7.7 y
10
0
0
1
2
3
4
5
6
7
8
9
10
years after randomization
No. at risk
ACVBP
318
307
296
286
271
236
206
163
126
80
34
CHOP plus
radiotherapy
329
314
292
280
265
231
199
152
113
70
28
Reyes F. et al, 2005 - NEJM
11
La radiothérapie n’a pas de place en première ligne
93-4 study : Event Free Survival
100
Probability
90
CHOP n = 277
80
CHOP plus radiotherapy n = 299
70
60
50
40
30
20
P = 0.5
med f-up= 7y
10
0
0
1
4
3
2
5
6
10
9
8
7
11
12
Years after Randomization
No. at risk
CHOP
277
220
202
179
157
130
112
87
66
39
19
1
CHOP plus
299
radiotherapy
249
226
193
170
143
112
90
64
48
30
9
Bonnet C, Fillet G, JCO 2007
La radiothérapie n’a pas de place en première ligne
93-4 study : Overall Survival
100
90
80
CHOP
n=277
CHOP plus radiotherapy
n=299
Probability
70
60
50
40
30
20
P = 0.5
med f-up= 7y
10
0
0
1
2
3
4
5
6
7
8
9
10
11
12
Years after Randomization
No. at risk
CHOP
277
249
226
206
178
153
131
102
75
45
22
1
CHOP plus
299
radiotherapy
265
243
211
187
155
123
98
68
50
30
9
Bonnet C, Fillet G, JCO 2007
Probability
MInT : overall survival
1.0
95%
0.8
86%
R-Chemo
Chemo
0.6
0.4
Lymphoma-associated deaths:
Chemo:
42
R-Chemo : 13
0.2
P = 0.0002
0
0
5
10
15
20
25
30
35
40
Months
Median observation time : 23 months
45
50
Pfreundschuh M, et al. Blood 2004; 104:40a (Abstract 157)
Lymphomes diffus
à grandes cellules B
Facteurs pronostiques et traitement
Traitement des formes avancées
chez le sujet agé
LNH 98.5 study : Design
 DLBCL
 Age 60–80 years
 No prior treatment
 PS 0–2
 Stage II–IV
Rituximab: 375 mg/m2 on day 1
Cyclophosphamide: 750 mg/m2 on day 1
Doxorubicin: 50 mg/m2 on day 1
Vincristine: 1.4 mg/m2 (up to 2 mg) on day 1
Prednisolone: 40 mg/m2/d days 1–5
R
A
N
D
O
M
I
Z
A
T
I
O
N
Rituximab
+
CHOP
q3wk x 8
CHOP
q3wk x 8
Coiffier B et al, N Engl J Med 2002;346:235
LNH-98.5 : Improved response
rate and quality of response with R-CHOP
ORR = 83 %
(n = 202)
100
Patients (%)
80
6
9
7
ORR = 69 %
(n = 197)
2
3
6
22
6
60
p = 0.005
40
76
63
Non-evaluable / other
Death during treatment
Progressive disease
Partial response
Complete response / CRu
R-CHOP vs CHOP
p = 0.005
20
0
R-CHOP
CHOP
Coiffier B et al, New Engl J Med 2002;346:235–242
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
7-year OS (%)
70-74 years
75-80 years
60-69
70-74
75-80
CHOP
40
41
21
R-CHOP
58
55
41
Overall survival in patients treated
with CHOP and R-CHOP(10 years FU)
Coiffier, B. et al. Blood 2010;116:2040-2045
Improved EFS and OS with R-CHOP is consistent
in clinical trials and clinical practice
N
GELA1
RICOVER-602
HOVON/NORDIC3
Intergroup USA4†
(Habermann)
MInT5
British Columbia6
Czech Republic7
399
Elderly (60–80)
1222
Elderly (61–80)
199
Elderly (65–80)
632
Elderly (> 60)
824
Young (18–60)
Low risk
292
All ages
376
Young
Chemo
Response (%)
Rituximab benefit
EFS or PFS
OS
CHOP-14 x 6
CHOP-14 x 8
76 vs 63
p = 0.005
78 vs 68
76 vs 72
CHOP-14 x 8
ND
< 0.01
0.05
CHOP-21
77 vs 76
0.003
0.05
CHOP-21
or others
86 vs 68
p < 0.0001
< 0.0001
0.0001
CHOP-like
ND
0.002
< 0.0001
CHOP-like
ND
0.0001
0.0007
CHOP-21 x 8
0.00002
0.0073
< 0.001
0.003*
* p-values for R-CHOP-14 x 6
† Secondary analysis without maintenance
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
RICOVER-60 : Improved TTF with
8 x rituximab + 6/8 x CHOP-14
6 cycles vs 8 cycles
R-CHOP-14 vs CHOP-14
1.0
1.0
8 x (R)-CHOP-14
(n = 415)
0.6
0.4
6 x (R)-CHOP-14
(n = 413)
0.2
0.8
Probability
Probability
0.8
8 x rituximab
+ 6/8 x CHOP-14
(n = 414)
0.6
0.4
6/8 x CHOP-14
(n = 414)
0.2
p = 0.000025 α-crit* = 0.031
p = 0.23
0
0
0
5 10 15 20 25 30 35 40 45
Time (months)
* R-CHOP-14 vs CHOP-14
0
5 10 15 20 25 30 35 40 45
Time (months)
Pfreundschuh M et al, Blood 2006;108:Abstract 205
LNH 03-6B : Study Design
R-CHOP14
+ IT MTX
R-CHOP14
3 months 3 months
C1 C2 C3 C4 C5 C6 C7 C8
Response
R
C1
C2
C3
C4
C5
C6
FUn
FU1
FU0
Response
Response
C7
FU0
C8
FU1
FUn
3 months 3 months
R-CHOP21
R-CHOP21
+ IT MTX
Filgrastim or Pegfilgrastim according to physicians’decision
Delarue et al Ash2009
Distribution of patients
Patients randomized
before January 1st, 2006
N = 202
R-CHOP14
N = 103
R-CHOP21
N = 99
Complete treatment received : N = 73
Premature withdrawal : N = 30
Complete treatment received : N = 74
No treatment received : N = 1
Premature withdrawal : N = 24
Dose-intensity
Is R-CHOP14 given
every 14 days ?
Median dose-intensity
R-CHOP14 R-CHOP21
Median
interval
between
two cycles
15 days
(9 – 70)
21 days
(19 – 63)
18/103 patients in R-CHOP14 group
received R-CHOP ≥ 18
R-CHOP14
R-CHOP21
CPM
84 %
96%
DOX
83 %
95 %
R-CHOP14 = 125 % of R-CHOP21
G-CSF use
R-CHOP14
R-CHOP21
90 %
68 %
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
LNH93-5: 60–70 y, poor prognosis
LNH93-1: young, good prognosis
% survival
% survival
Doxorubicin
75 mg/m² d1
100
ACVBP
Cyclophosphamide 1200 mg/m² d1
Vindesine
2 mg/m² d1, d5
80
Bleomycin
10 mg
d1, d5
PrednisonCHOP
60 mg/m² d1 to d5
60
MTX intra-thecal
15 mg
d2
G-CSF
5 µg/kg d6 to d13
100
80
60
40
40
20
20
ACVBP
CHOP
P = 0.03
P = 0.03
0
0
0
1
2
3
4
5
6
7
8
9
Years
Reyes F et al. NEJM 2005
0
2
4
6
8
Years
Tilly H et al. Blood 2003
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
Matched control study : Progression free survival
75%
R-ACVBP
ACVBP
60%
PFS
Follow-up (months)
Follow-up (months)
study
LNH03-3
LNH98-3
N
181
181
Median
27
26
Min
0
0
Max
44
47
CH, Berlin EHA 2009
Survival with ACVB in LNH Regimens
(in randomized studies)
R-ACVBP
3116 patients
R-CyclOBEAP in young patients
with high-risk DLBCL
Niitsu N, Int J Hematol 2010; 92 : 231-237
Mega-CHOEP with and without Rituximab, Patients with DLBCL: EFS
EFS
1.0
.9
.8
with Rituximab
n=64
.7
.6
p=0.013
.5
without Rituximab
.4
n=29
.3
.2
.1
0.0
0
1
2
3
4
5
6
Time (years)
Glass et al: Ann Oncol 2010, Epub doi:10.1093/annonc/mdq235
77
DSHNHL 2002-1 -- R-MegaCHOEP
study design after amendment 1
for CD20-pos. B-NHL
mCHOEP I
CYC 1500
ADR 70
VCR 2
ETO 600
PRD 500
1
14
PBSC
PBSC
PBSC
mCHOEP II
CYC 4500
ADR 70
VCR 2
ETO 960
PRD 500
mCHOEP III
CYC 4500
ADR 70
VCR 2
ETO 960
PRD 500
mCHOEP IV
CYC 6000
ADR 70
VCR 2
ETO 1480
PRD 500
22
36
43
56
64
77
98
days
R
1
15
29
43
57
71
85
CHOEP-14
CYC 750
ADR 50
VCR 2
ETO 300
PRD 500
PRD and VCR doses are
absolute, all others are per m²
Rituximab (375mg/m²)
99
DSHNHL 2002-1 -- MegaCHOEP
Progression-free survival
1
p=0.119
0.9
0.8
0.7
0.6
0.5
0.4
R-CHOEP-14
0.3
R-MegaCHOEP
0.2
0.1
0
0
10
20
30
40
Months
50
60
70
DSHNHL 2002-1 -- MegaCHOEP
Overall survival
1
p=0.142
0.9
0.8
0.7
0.6
0.5
0.4
R-CHOEP-14
0.3
R-MegaCHOEP
0.2
0.1
0
0
10
20
30
40
Months
50
60
70
Greb A et al, Cancer Treatment Reviews 2007; 33 : 338-346
Lymphomes diffus
à grandes cellules B
Facteurs pronostiques et traitement
Traitement des rechutes
OS (intent to treat)
Gisselbrecht C et al, J Clin Oncol 2010; ahead of print, July 26
PFS undergoing ASCT (ITT)
Gisselbrecht C et al, J Clin Oncol 2010; ahead of print, July 26
Aggressive B-NHL –
CORAL Trial - PFS
PROGRESSION-FREE SURVIVAL
ACCORDING TO PRIOR RITUXIMAB
(INDUCTION ITT)
PROGRESSION-FREE SURVIVAL
ACCORDING TO FAILURE FROM
DIAGNOSIS (INDUCTION ITT)
62%
N=147
30%
64%
N=160
N=241
Gisselbrecht et al JCO 2010, Epub
31%
N=228
Aggressive B-NHL –
CORAL Trial Response- EFS
Failure from diagnosis > 12 months
Failure from diagnosis =< 12 months
N= 106
N= 41
N= 54
N= 187
Gisselbrecht et al JCO 2010, Epub
Aggressive B-NHL
Allogeneic and autologous SCT in aggressive B cell lymphoma
DSHNHL R3 (B cell lymphoma):
HDT + allogeneic SCT
DSHNHL
CORAL:
HDT + autologous SCT
1.0
0.9
Probability of EFS
Probability of EFS
0.8
0.7
No prior rituximab: 54.6 (22,9-78,0)%, n=11
0.6
0.5
0.4
0.3
prior rituximab: 34,6 (19,9-49,7)%, n=45
0.2
0.1
0.0
0
12
24
36
48
60
72
0
12
24
36
48
Time after Transplant (Months)
87
Allogeneic SCT in relapsed DLBCL
Reduced intensity conditioning : Results
NRM
OS
PFS
RR
sens
ref.
Thomson et al. JCO 2009; 27 (3): 426
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
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-CHOP
Phase I (Tilly H. et al, ongoing)
Phase III study testing a maintenance with lenalinomide
REMARC study
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 myéloablatif est une option en cas de mauvais pronostic