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B-CLL
DIAGNOSIS
PROGNOSIS
CLINICAL MANAGEMENT
MRD MONITORING
THERAPY
CLL TherapyGeneral Considerations
• Treat only patients with symptomatic or progressive disease
• Treatment based on biological factors not justified
• Include patients in trials whenever possible• Never forget that the ultimate goal of therapy is
to prolong survival • Treat the patient, not the disease
CLL TherapyIndici di attività
• Sintomi B (febbre, sudorazione notturna, perdita di peso)
• Insufficienza midollare (-Hb, -Plt, -Neu)
• Splenomegalia progressiva
• Adenomegalie progressive
• LDT < 6 o 12 mesi
CLL TherapyCriteri di Risposta (NCI WG, 1996
Remissione Completa• assenza di adenopatie, splenomegalia ed epatomegalia • assenza di sintomi sistemici • linfociti inferiori a 4000/µL • neutrofili superiori o uguali a 1500/µL • piastrine superiori a 100000/ µL • Hb uguale o superiore a 11g/dL • alla biopsia osteomidollare normale cellularità e infiltrato linfatico inferiore al 30%
Remissione Parziale• riduzione delle adenopatie pari o superiore al 50% • riduzione della splenomegalia o dell'epatomegalia pari o superiore al 50% • riduzione della linfocitosi pari o superiore al 50% • >più uno o più dei seguenti:• - neutrofili pari o superiori a 1500/µL, o miglioramento del 50% rispetto ai valori di base
- piastrine superiori a 100000/µL o miglioramento del 50% rispetto ai valori di base- Hb superiore a 11 g/dL o miglioramento del 50% rispetto ai valori di base- assenza di sintomi sistemici
Malattia Stabile• Non RP nè progressione
010
20304050
60708090
100
1970 1980 1990 2000
CR%
Chlorambucil
COP, CHOP
FludarabineFludarabine
Fludarabine-combined regimens
Year
Symptoms palliation
Higher response rate(vs. Chlorambucil)
Prolonged FFPProlonged FFP
MRD (-)? Prolonged survival
? Cure
CLL: CR rate and treatment goals over the years
E. Montserrat - Inside Blood 2005
CLL Treatment in a Nutshell
RANDOMIZED STUDIES
• Fludarabine (Cladribine) > Chlorambucil• Fluda + Cyclophosphamide > Fluda• Fluda + Cyclo (oral) = Fluda + Cyclo (i.v)
SINGLE ARM STUDIES• Fluda + Rituximab• FCR• FCM…
Risultati CLB I linea
Trials Dosaggio Risultati
FRE-CLL-80
( 278 pz )0,1 mg/die CR: 45%
PR: 31%NR: 24%
FRE-CLL-85
( 437 pz )
0,3 mg/Kg d 1-5 +PDN 40/mq d 1-5
CR: 28%PR: 41%NR: 31%
RISULTATI CLB I linea IGCI CLL-01 trial
Risposta Alte dosi Dosi intermedie
CR 70 % 31 %
PR 19 % 19 %
NR 11 % 50 %
Risultati CLB mantenimento
Riferimenti Dosaggio Risultati
Jaksic et al. Nouv Rev Fr Hematol, 1988
15 mg 2 volte settimana/ 3 anni
Migliora la durata della risposta e la sopravvivenza
Risultati CLB II linea
Riferimenti Popolazione Risultati
Robak et al. Blood, 2000
Resistenti agli analoghi delle purine
OR: 33%
Ray et al.N Engl J Med, 2000
Resistenti alla FAMP
OR: 7%
HD-CLB versus CHOP mod.
• Arruolati 228 pazienti in stadio avanzato
• OR HD-CLB: 89,5% CHOP: 75% p<0,001
• CR HD-CLB: 59,5% CHOP: 30,4%
• OS HD-CLB: 68 m. CHOP: 47 m. P<0,005
Jaksic et al. Cancer,1997
CHOP versus COP• French Cooperative Group on CLL:
“Long- term results of the CHOP regimen in stage C chronic lymphocitic leukaemia”.
Br J Haematol, 1989
OS mediana = 22 mesi COP OS mediana = 62 mesi CHOP ( p = 0,001 )
ANALOGHI PURINICIANALOGHI PURINICI
1)1) FludarabinaFludarabina (9- (9---arabinosil-2-fluoroadenina) arabinosil-2-fluoroadenina)
2)2) 2CdA 2CdA (2-cloro-2’-(2-cloro-2’-deossiadenosina)deossiadenosina)
3)3) dCFdCF (2’-deossicoformicina) (2’-deossicoformicina)
MECCANISMO DI AZIONEMECCANISMO DI AZIONE
1)1) effetto inibitorio su enzimi effetto inibitorio su enzimi implicati nella riparazione e implicati nella riparazione e sintesi del DNAsintesi del DNA– DNA primasi, ligasi e polimerasiDNA primasi, ligasi e polimerasi– Reduttasi ribonucleotidica Reduttasi ribonucleotidica
2)2) danno diretto della membrana danno diretto della membrana dei mitocondridei mitocondri
3)3) inibizione della sintesi di RNAinibizione della sintesi di RNA
FAMP IN PAZIENTI FAMP IN PAZIENTI PRETRATTATI PRETRATTATI
Refer. RC OR
OS media
naN°pz.
GreverNouv Rev Fr
Hematol: 1988
3%
(13%)12%
(32%)13 m
32(31)
KeatingBlood 74:
1989
13%(13%)
57%(48%)
11 m68
(48)Johnson Ann Oncol
142 [a277]:1994
5% 26% 12.7 m 123
Sorensen JCO 15:1997
3% 32% 13 m 724
2-CDA IN PAZIENTI 2-CDA IN PAZIENTI PRETRATTATI PRETRATTATI
Refer. RC OROS
medianaN°pz
PiroBlood
72:19880 22%
Non riportata
18
SavenLeuk Lymph
5: 19934% 40%
Non riportata
90
JuliussonAnn Oncol
7:199631% 58%
36 m (CR) 28 m (PR)
52
RobakBr J Hematol
108:200012% 48% 12 m 184
FAMP FRONT-LINEFAMP FRONT-LINE
Trattamento
N° pz. RC OR PFS mediana
OS median
a
Ref.
FAMP 25-30 mg/m2 d 1-5 (71 pz) opp.
FAMP 30 mg/m2 d 1-5 + PDN 30
mg/m2 (103)
174I/II 108III/IV 66
29% 78%
31 mRC = 37
m p=0.02RP = 30
m
63 mKeating Blood
92:1998
FAMP 25 mg/m2 d 1-5 16 31% 100% Non
riportata
Non riportat
a
Clavio EurJHem61:1998
FAMP 30 mg/m2 d 1-5 17 65% 94%
n.r. [FUP 13
m (2-38)]
Non riportat
a
Stelitano Haemat84:1999
FAMP FRONT-LINEFAMP FRONT-LINE
Keating MJ et al. Blood 92:1998
OS by treatment OS by response
PFS by response
2-CDA FRONT-LINE2-CDA FRONT-LINE
RC ORRFS
medianaOS
medianaMorti
Popolazione totale194 pz
45.4%
82.5%
12 (3-54) 18 m 63
2-CdA 0.12 mg/kg d 1-
543 pz
37.2%
72.1%
16 (3-54) 19 m 15
2-CdA+PDN 30 mg/m2
d1-5151 pz
47.7%
85.4%
12 (3-43) 18 m 48
Robak T et al. Br J Haem 108:2000p=0.04
FAMP FAMP vsvs CHL CHLTrattamento N°
pz.RC RP RFS OS Ref.
FAMP 25 mg/m2
Chl 40 mg/m2 ogni 28 gg.
170
181
20%p<0.001
4%
43%p<0.00
1
33%
25 mp<0.00
1
14 m
66 mp=0.
156 m
Rai et al. NEJM
24: 2000
FAMP 25 mg/m2 x 6
Chl 30 mg/m2 g 1 e 15+PDN 40 mg/m2 g 1-5 e 15-19 ogni 28 gg
69 73
46%p-NC
37%
25%p-NC
34%
28 mP=0.00
7
21 m
NCSpriano Hematol
Cell Ther Abs 2000
FAMP 25 mg/m2
ogni 21 gg (per 18 sett)Chl 10 mg/m2/d
per 18 sett
39
35
39%p=0.29
43%
36%p=0.29
43%
p=0.92 p=0.3
Jaksic Hematol
Cell Ther Abs 2000
FAMP FAMP vsvs CHL CHL
Rai et al. NEJM, 343: 24, 2000
RFS p<0.001
PFS p<0.001
OS p<0.21
FAMP + CY (non comparativi)FAMP + CY (non comparativi)
Trattamento
N° pz.
Stadio
RC OR PFS mediana Ref.
FAMP 30 mg/m2 d 1-3+ CY 300
mg/m2 d 1-3
128(34*)
III-IV 47%
17% (35%)
74% (88%)
12-38 m Non
raggiunta
O’ Brien JCO
19:2001
FAMP 30 mg/m2 d 1-3
+CY 250 mg/m2 d 1-3
32(15*)
A 3%B
50%C
47%
16% 91%
Durata mediana
della risposta non
raggiunta dopo FUP 14
m
Hallek,B J
Haemat114:200
1
FAMP per os 30
mg/m2 d 1-5 +CY per os 200 mg/m2
d 1-5 x 6
59*
B 79%
C 21%
47% 78% Non riportata
Cazin [a772] Blood
98:2001
* non pre-trattati
TTP FAMP TTP FAMP vsvs FAMP+CY FAMP+CY
O’ Brien S et al. JCO 19: 2001
FAMP+CY: TTP mediano n.r.
FAMP: TTP mediano 30 mesi
FAMP ORALEFAMP ORALE
Trattamento
N° pz.
RC OR PFS mediana
OS mediana
Ref.
FAMP 40 mg/m2 d 1-5 x 6-8 cicli
78* 21% 46%Non
riportata
Non riportat
a
Boogaerts JCO
15:2001
FAMP 40 mg/m2 d 1-5 x 6-8 cicli
81 37% 72% 28 m Non
riportata
Rossi JF JCO
22:2004FAMP per
os 30 mg/m2 d 1-5 +CY per os 200 mg/m2 d 1-5
x 6 cicli
59 47% 78%Non
riportata
Non riportat
a
Cazin [a772] Blood
98:2001
* Pretrattati con alchilanti (rec+res)
MoAbs citotoxic mechanisms
Effector cells/Complement
Apoptosis Radionuclide Toxin/Antibiotic
MoAbs for CLLMoAbs for CLL
Antibody Antigen
Alemtuzumab (Campath-1H) CD52
Rituximab (Rituxan, Mabthera) CD20
Epratuzumab (LymphoCide) CD22
Hu-1D10 (Apolizumab) HLA-DR
IDEC-152 (Lumiliximab) CD23
IDEC-114 CD80
Bevacizumab (Avastin) VEGF
BL-22 CD22( conjugate with Pseudomonas)
Alemtuzumab (anti-CD52) antibody
IgG1 humanised antibody:Low immunogenicity
CD52 antigen: Highly expressed on
all lymphocytesmonocytes and macrophages
spermatozoaeosinophils
Not expressed on haemopoietic stem cells
Does not modulate/shed Also expressed on the
majority of malignant lymphocytes
Number of fludarabine-refractory pts 36 Pts with p53 mutations or deletions 15 (42%) Clinical responses in p53 mutated/deleted 6/15 (40%) Clinical responses in pts without 4/21 (19%) Median duration of response 8 months
- Alemtuzumab is active in CLL pts with p53 mutations or deletions
Lozanski G et al, Blood,2004
Alemtuzumab in B-CLL with p53 mutations and deletions
patients: number: 41; 38 evaluable for Response age: 66 (44-75) Rai: I: 10%; II: 21%; III: 54%; IV: 15% B-symptoms: yes: 63%; no: 37%
therapy: Dosis escalation from 3-10-30 mg s.c. Campath-1H in week 1; 30 mg 3x /week s.c. (week 2 - 18) duration: 12-18 weeks prophylaxis: Cotrimoxazol, Acyclovir, Fluconazol
Lundin et al, Blood,2002
CAMPATH-1H AS FIRST LINE TREATMENT OF CLL
subcutaneoussubcutaneous
First line treatment of CLL with CAMPATH-1H results
Response: 87% (19% CR, PR 68%) Rai stage I-II 100% <65 y 83%; > 65 y 90%
TTF: 18+ months (7 - 44+ months)
side effects: -fever: 70% (68% Gr. 1-2; 2% Gr. 3) -skin reactions: 90% (88% Gr. 0-II; 2% Gr. 3) -infections: 4x CMV-reactivation, no severe
bacterial infection
Lundin et al,Blood, 2002
Eradication of MRD in B-CLL after alemtuzumab (ALZ) therapy is associated
with prolonged survival
Patients: 91 pretreated (44 refractory to purine analogs) Treatment: 30 mg i.v. TIW, 9 weeks Response: 32 CR (36%), 17 PR (19%), 42 NR (46%)
22/44 (50%) refractory to PA responded Longer median survival in MRD-negative pts Longer TFS in MRD-negative pts, not reached; MRD+CRs, 20
months; PRs, 13 months; NR, 6 months (P<0.0001) OS in 18 pts MRD- CR was 84% at 60 months.
MRD-negative CR in CLL is achievable with ALZ, leading to an improved OS and TFS
Moreton P, et al,JCO, 2005
CMV infection during alemtuzumab treatment
• Monitoring for CMV
• Usually fever without pneumonitis, rapidly responding to ganciclovir
• Incidence: CLL ≈ 10-40%
• If patient is well and CMV test is positive:
– Confirm CMV test
– If second CMV test is positive it is recommended that alemtuzumab is stopped and patient is treated with ganciclovir
• If patient is symptomatic:
– Treat at once if patient is CMV PCR positive
– Perform bronchoscopy and broncho-alveolar lavage if patient is CMV PCR negative
MabThera®: a chimeric murine/human MoAb
Variable murine regions bounding CD20 on B cells
Human kappa costant regions
Human domain IgG1 Fc, synergistic with human effector mechanisms
Chimeric IgG1
Rituximab monotherapy in CLL (375mg/m2/wk x 4)
Investigator, year
No of Pts
Prior Rx ORR (% )
CR (% )
Itala, 2002 24 Yes 35 -
Huhn, 2001 29 Yes 23 -
Winkler, 1999
10 Yes 10 -
Nguyen, 1999
15 Yes 7 -
Hainsworth, 2003
44 No 51 4
Rituximab monotherapy in CLL (schedules other than
375mg/m2/wk x 4)
Investigator, year
No of Pts
Regimen mg/ m2/ wk
Prior Rx ORR (% )
CR (% )
O’Brien, 2001 40 375 x 1
500 – 2250 x 3
Yes 22-75 -
Byrd, 2001 33 250-375 x3/ w x 4
Yes and No
45 3
Hainsworth, 2003
44 375 x 4 + 4 No 51/ 58 4/ 9
Thomas, 2001
31 375 x 8 No 90 19
Summary of response data in Phase II studies of rituximab plus
chemotherapyInvestigator, Yr No of Pts Regimen Prior Rx ORR (% ) CR
(% )
Schulz, 2002 31 F (25 mg/ m2 ) q5 d x 2 then FR (375 mg/ m2) x 2 then R x 2
Yes and No
87 33
Byrd, 2003 53
51
Sequential F x 6 then R x 4
Concurrent F and R x 6
No 77
90
28
47
Lamanna, 2003 30 Sequential F (25 mg/ m2 ) q5 d x 6, then HDC (3 g/ m2) q1 x 3 then R (375 mg/ m2) x 4
No 86 57
Keating, 2005
JCO
224
FCR: Cycle 1: R -375 mg/ m2 d1; std doses C, F d 2 - 4. Cycles 2-6: R-500 mg/ m2 d1; C, F d 1 - 3
No 95 70
Wierda, 2005
JCO
177
FCR: Cycle 1: R -375 mg/ m2 d1; std doses C, F d 2 - 4. Cycles 2-6: R-500 mg/ m2 d1; C, F d 1 - 3
Yes 73 25
Keating et al, JCO 2005
Keating et al, JCO 2005
PATIENT CHARACTERISTICS I o Observation time 1998-2004o N° of patients 60o M/F 30/30o Median age (range) 59 (37-74) o Modified Rai stage:
Low risk (0) 5 Intermediate risk (I + II) 52 High risk (III + IV) 3
o ECOG (Performance Status): 0 37 1 19 2 4
PATIENT CHARACTERISTICS II o B symptoms 17o Time since first diagnosis:
1 year 17 2-5 years (I + II) 29 > 5 years 14
o Infiltration pattern BM: Nodular 4 Mixed 10 Diffuse 46
FLUDARABINE + RITUXIMAB FOR PREVIOUSLY UNTREATED
CLL
patients with CR, PR, or stable disease
received
Rituximab (375mg/m2
weekly x 4)
Fludarabine
25mg/m2
MabThera
375mg/m2
Weeks
40 days Range 30- 155
1 5 9 13 17 21 1 2 3 4
Weeks
MATERIALS AND METHODS
ZAP-70 protein TK and CD38 antigen were determined by multicolor flow cytometric methods (Crespo et al, 2003; Del Poeta et al,2001).
A cut-off of 20% was used for ZAP-70 and CD38.
The threshold for MRD positivity was set at >5% CD19+CD5+CD79b- CLL cells in bone marrow.
MRD flow analysis after chemotherapy with fludarabine CD19+CD5+ = 0.6%
0 256 512 768 1024
B aldas s a ri A . pos tC HT.002FSC -Height ->
10 10 10 10 100 1 2 3 4
B aldas s a ri A . pos tC HT.002C D19 PerC P ->
10 10 10 10 100 1 2 3 4
B aldas s a ri A . pos tC HT.002C D79b FITC ->
10 10 10 10 100 1 2 3 4
B aldas s a ri A . pos tC HT.002C D79b FITC ->
10 10 10 10 100 1 2 3 4
B aldas s ari A. pos tC HT.002C D79b FITC ->
10 10 10 10 100 1 2 3 4
B aldas s ari A. pos tC HT.002C D19 PerC P ->
10 10 10 10 100 1 2 3 4
B aldas s ari A. pos tC HT.002C D20 PE ->
TOXICITY (WHO)
Grade 0
Grade 1
Grade 2
Grade 3 Grade 4
Fever/Chills 0 5 0 0 0Anemia 0 0 3 0 0Neutropenia
0 7 5 19 10
Thrombocytopenia
0 2 2 2 1
InfectionsHerpes simplexHerpes zosterPneumoniaAcute hepatitis
77
3
3
2
2
1
1
78,3%
15,0%6,7%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
p
a
t
i
e
n
t
s
CR PR NR
RESPONSE TO RITUXIMAB AND FLUDARABINE
NCI criteriaNCI criteria
((47/60)47/60)
FLUDARABINE AND RITUXIMABFLUDARABINE AND RITUXIMAB
((9/60)9/60) ((4/60)4/60)
CLINICAL OUTCOME I Median follow up duration was 27 months (9/56 pts Median follow up duration was 27 months (9/56 pts [[16%16%] have experienced a relapse).] have experienced a relapse).
Median duration of CR and PR was not reachedMedian duration of CR and PR was not reached..
Progression-Free Survival
Months from Treatment
Rate
wit
h c
on
tin
uin
g r
esp
on
se
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
68% at 3 years
CLINICAL OUTCOME II Among the 60 pts enrolled, 6 have died: 1 in CR Among the 60 pts enrolled, 6 have died: 1 in CR (fulminant B hepatitis), 2 resistant to fludarabine for PD, 3 (fulminant B hepatitis), 2 resistant to fludarabine for PD, 3 for PD after protocol therapy).for PD after protocol therapy).
Overall Survival
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Su
rviv
ing
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 84
85% at 5 years
2832
19
41
15
45
0
10
20
30
40
50
p
a
t
i
e
n
t
s
ZAP- 70+
ZAP- 70-
CD38+
CD38-
MRD+
MRD-
INCIDENCE OF ZAP-70, CD38 AND MRDINCIDENCE OF ZAP-70, CD38 AND MRD
MRDMRDCD38CD38ZAP-70ZAP-70
46.746.7%%
31.731.7%%
25%25%
57
97
58
88
0
10
20
30
40
50
60
70
80
90
100
C
R
(%)
ZAP- 70+
ZAP- 70-
CD38+
CD38-
CR (%) BY ZAP-70 AND CD38 CR (%) BY ZAP-70 AND CD38
P = P = 0.020.02
P = P = 0.00090.0009
Min-Max
25%-75%
Median value
CD20 MFI and Response to Rituximab
Response to Rituximab
CD
20 M
FI
0
40
80
120
160
200
0 1 2 3CRPR/NR
P = 0.007
PROGRESSION FREE SURVIVAL BY ZAP-70, CD38 and MMR
ZAP70 -
ZAP70+
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Pro
gre
ssin
g
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
P = 0.00005
CD38 -
CD38+
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Pro
gre
ssin
g
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
P = 0.0002
MMR-
MMR+
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Pro
gre
ssin
g
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
P = 0.001
OVERALL SURVIVAL BY ZAP-70, CD38 and MMR
ZAP70-
ZAP70+
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Su
rviv
ing
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 84
P = 0.006
CD38-
CD38+
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Su
rviv
ing
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 84
P = 0.05
MMR-
MMR+
Months from Treatment
Cu
mu
lati
ve P
rop
ort
ion
Su
rviv
ing
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 84
P = 0.002
CONSIDERATIONS CONSIDERATIONS
The The additionaddition of MoAbs, such as of MoAbs, such as rituximabrituximab, to , to chemotherapychemotherapy, allowed us a , allowed us a better outcomebetter outcome in B-CLL exerting a key in B-CLL exerting a key role to role to eradicate MRDeradicate MRD..
The The stratification stratification of patients in of patients in different different risk classesrisk classes using using ZAP-70ZAP-70 and and CD38CD38, , allowed us to distinguish different clinical allowed us to distinguish different clinical outcome subsets: we can offer more outcome subsets: we can offer more tailored treatmenttailored treatment strategies based on this strategies based on this approach.approach.
TransplantationTransplantation procedures or procedures or experimental therapiesexperimental therapies should be should be specifically reserved to specifically reserved to “high risk” “high risk” ((ZAP-ZAP-70+ or CD38+70+ or CD38+)) B-CLL subsets.B-CLL subsets.
N
um
ber
CLL Autologous
CLL Allogeneic
0
50
100
150
200
250
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year
Stem-cell transplants in CLL - EBMT
Allogeneic SCT for CLLWhy?
• Increasing number of patients treated with “best” chemo- chemo/immunotherapies upfront difficult to be “rescued” with conventional therapies
• Autologous transplantation– not indicated (patients do not achieve CR)
– all patients relapse
– risk of MDS/AML
Auto Allo
Upper age limit 70 50 - 60
TRM (4 yrs) 10% 25-50%
RR (4 yrs) 50% 10-25%
Survival (4 yrs) 40-70% 40-60%
Survival (8 yrs) 30-40% 35-55%
Plateau no yes
Stem-cell transplants in CLL
Overall survival after stem cell transplantation
AlloSCT (n = 46)
AutoSCT (n = 139)
0 2 4 6 8 10 12 14 16 18
Years
0
0.2
0.4
0.6
0.8
1
Pro
bab
ility
Montserrat E, Hematol Oncol Clin N Am 2004; 18:915–926.
0 2 4 6 8 10 12 14 16
Years
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Ris
k o
f re
lap
se
Auto - SCT (n=122)
Allo - SCT (n=38)
Montserrat E, Hematol Oncol Clin N Am 2004; 18:915–926.
Relapse rate after stem cell transplantation
CLL Treatment Goals/Interventions
Palliation Chlorambucil, Epo, etc.
Response Fludarabine + Cycloph.
MRD - FCR, FCM (R-FCM)
Cure Allogeneic SCT
Recommended