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Management of Recurrent of Relapsed and Refractory Hodgkin Lymphoma. Michael Crump, MD, FRCPC Division of Medical Oncology & Hematology Princess Margaret Hospital Department of Medicine, University of Toronto. Outline of this talk. prognostic factors following disease recurrence - PowerPoint PPT Presentation
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Management of Recurrent of Relapsed Management of Recurrent of Relapsed and Refractory Hodgkin Lymphomaand Refractory Hodgkin Lymphoma
Michael Crump, MD, FRCPCDivision of Medical Oncology & Hematology
Princess Margaret HospitalDepartment of Medicine,
University of Toronto
Outline of this talkOutline of this talkOutline of this talkOutline of this talk
• prognostic factors following disease recurrence • role of local radiotherapy
• current results with ASCT
• strategies to improve ASCT outcome
• standard approaches – chemotherapy
• second transplants- reduced intensity allogeneic SCT
Recurrent HLRecurrent HL
• ~10-20% of early stage (I and II), 20-40% of pts with advanced disease
• Refractory: progression during or within 3 mos of completing therapy
Prognostic factors at relapsePrognostic factors at relapse
• age
• B symptoms
• performance status
• time to recurrence
• anemia
• extranodal sites
• primary treatment (RT v chemo)
… etc
Importance of time to Importance of time to recurrencerecurrence
GHSG: 472 pts with relapse / 4754
Median f/u 45 mos
FFTF survival
Early (< 1y) 33% 46%
Late (> 1y) 43% 79%
Josting et al. JCO 2002
Outcome of relapsed HL according to number of risk factors
(anemia, early relapse, stage III,IV)
Impact of clinical variables in transplant eligible patients
Age <60, KPS 90-100)
Outcome of Patients Experiencing Outcome of Patients Experiencing Relapse After ABVD x 2 + RT for Early-Relapse After ABVD x 2 + RT for Early-
Stage Favorable HLStage Favorable HL
• Uncommon occurrence: 3-5% of patients on recent trials of NCIC, GHSG
• eg: 42 / 1127 pts on GHSG trials– 8 ref, 7 early, 27 late (>12 m)– Rx: 4 RT, 14 chemo, 24 ASCT
Outcome of Patients Experiencing Outcome of Patients Experiencing Relapse After ABVD x 2 + RT for Early-Relapse After ABVD x 2 + RT for Early-
Stage Favorable HLStage Favorable HL
3y FFTF: 52%
3 y OS : 67%
Factors associated with poor outcome:
• anemia• advanced stage• early relapse
Sieniawski et al. J Clin Oncol 2007
Management of very late relapseManagement of very late relapse
• No risk factors (normal hemoglobin, limited stage), CR1 >5 y
→ chemotherapy + IFRT (EFRT?)
• eg BEACOPP x 4
• ASCT reserved for subsequent relapse
Primary Refractory HL
• New lesions or progression of prior lesions within 3 months of completing therapy
Josting A et al. J Clin Oncol 2000
Outline of this talkOutline of this talkOutline of this talkOutline of this talk
• prognostic factors following disease recurrence • role of local radiotherapy
• current results with ASCT
• strategies to improve ASCT outcome
• standard approaches – chemotherapy + rads
• second transplants- reduced intensity allogeneic SCT
Radiation After Relapse – Consider Radiation After Relapse – Consider it an Optionit an Option
• radiation as component of combined modalitytherapy for HL reduces the risk of local recurrence
• HL often recurs in nodal sites, and in sites not previously irradiated
• long-term disease control has been reportedafter RT for recurrent HL after primarychemotherapy (or CMT)
Poen et al. Int J Rad Onc Bio Phys 1996Mundt et al. Int J Rad Onc Bio Phys 1995
Radiation as Salvage TherapyRadiation as Salvage Therapy
1) Josting et al (GHSG): non-randomized: 100 pts
62% advanced HL at dx68% prior radiotherapy40% in-field relapse
5 yr FFTF 28% OS 51%
2) Wirth et al (Melbourne): 16 pts - 2 or 3 prior regimens
5 yr FFS 14% OS 38%
1) J Clin Onc 20052) Int J Rad Onc Bio Phys 1997, 2005
Favourable outcome:Stage INo B sx
Outline of this talkOutline of this talkOutline of this talkOutline of this talk
• prognostic factors following disease recurrence • role of local radiotherapy
• current results with ASCT
• strategies to improve ASCT outcome
• standard approaches – chemotherapy + rads
• second transplants- reduced intensity allogeneic SCT
Autologous Stem Cell Transplant Autologous Stem Cell Transplant in HLin HL
• Standard of care for relapsed and/or refractory disease
• 2 RCTs demonstrated improvement in
3-year Freedom from Treatment Failure with ASCT vs conventional chemotherapy
• Schmitz, Lancet 2002: 75% vs 45%• Linch, Lancet 1993: 55% vs 34%
Autologous stem cell transplantation for Autologous stem cell transplantation for relapsed/refractory HLrelapsed/refractory HL
Autologous stem cell transplantation for Autologous stem cell transplantation for relapsed/refractory HLrelapsed/refractory HL
dexa-BEAM x 2R
dexa-BEAM x 2
dexa-BEAM x 2R
dexa-BEAM x 2n=161n=161
ASCTASCT 49%49% 57%57%
ChemoChemo 32%32% 56%56%
p = 0.02p = 0.02
ASCTASCT 49%49% 57%57%
ChemoChemo 32%32% 56%56%
p = 0.02p = 0.02
FFTF (7 y)FFTF (7 y) OSOSFFTF (7 y)FFTF (7 y) OSOS
Schmitz et al. ASCO, 2005Schmitz et al. ASCO, 2005
ASCT
dexa-BEAM x 2
ASCT
dexa-BEAM x 2n=117n=117
+ IFRT
??Regimen
No. of Patients
CR%95% CI
PR%95% CI
ORR%95% CI%
Gr 3/4PMN/PLT
%
Toxic deaths %
Dexa-
BEAM
144 27
20-34
54
46-62
81
75-87
NS 5
1-9
Mini-
BEAM
55 49
35-63
33
21-47
82
69-91
86/60 2
0.1-10
ICE 65 26
16-39
59
46-71
85
74-92
NS 0
0-5
DHAPq2w 102 21
13-29
68
59-77
89
83-95
88/69 0
0-4
GDP 23 17
5-39
52
31-73
69
47-87
9/13 0
0-15GVD 38 11
3-2553
36-6964
46-7869/17 0
0-9
IEV 51 76
60-88
84
71-93
100/NS 0
MINE 157 NS NS 75
64-84
NS 5 (3)
IV 47 45
30-60
38
25-54
83
69-92
65/0 NS
Long – term outcome: Long – term outcome: Royal Marsden HospitalRoyal Marsden Hospital
Ann Oncol 2008
5y 10yPFS 44% 37%OS 55% 49%`
Multivariate Analysis: Prognosis determined by:
sensitivity to salvage chemotherapy
Hasenclever index
Predictors of outcome post-ASCT Predictors of outcome post-ASCT for relapsed/refractory HLfor relapsed/refractory HL
Predictors of outcome post-ASCT Predictors of outcome post-ASCT for relapsed/refractory HLfor relapsed/refractory HL
• CR/PR at ASCT
• first remission >1 yr
• negative pre-ASCT
FDG-PET
• CR/PR at ASCT
• first remission >1 yr
• negative pre-ASCT
FDG-PET
• resistant to 2nd line chemo
• high # HL PI risk factors
• multiple relapses
• primary refractory HL
• resistant to 2nd line chemo
• high # HL PI risk factors
• multiple relapses
• primary refractory HL
Less favorableoutcome
Less favorableoutcome
More favorableoutcome
More favorableoutcome
Gopal AK, et al. Cancer 2008Sirohi B, et al. Ann Oncol 2008Wadehra N, et al. Biol Blood Marrow Transpl 2006Ferme C, et al. J Clin Oncol 2003
Gopal AK, et al. Cancer 2008Sirohi B, et al. Ann Oncol 2008Wadehra N, et al. Biol Blood Marrow Transpl 2006Ferme C, et al. J Clin Oncol 2003
PMH: Mobilization and PMH: Mobilization and ASCTASCT
– PBSC Mobilization• Cyclophosphamide 2 g/m2 on day 1• Etoposide 200 mg/m2 days 1 – 3 • G-CSF 10 g/kg starting on day 6
– High-dose chemotherapy regimen• Etoposide 60 mg/kg on day -4• Melphalan 180 mg/m2 on day -3
– Involved field RT given if bulk disease ( 5 cm) present at relapse, 6-8 weeks post-ASCT
Stem Cell Mobilization Stem Cell Mobilization EfficiencyEfficiency
GDPGDP Mini-BEAMMini-BEAM PP value value
# apheresis sessions(median, range)
1 (1 – 3) 1 (1 – 5) 0.23
Median CD34+ cellsX 106 /kg
11.1 (1.4 – 37.1)
5.5 (0 – 41.7) 0.0018
% patients with collection 2 X 106 /kg
97 82 0.07
Proportion collected in a single apheresis (%)
90 57 0.0043
% patients with collection > 5 X 106 /kg
97 57 0.0003
Proportion collected in a single apheresis (%)
73 36 0.004
Proportion requiring marrow harvest (%)
3 18 0.07Kuruvilla et al. Cancer 2006
Results – Response and Results – Response and SurvivalSurvival
GDP Mini-BEAM p
Response Response Rate (%)Rate (%)(95% CI)(95% CI)
6262
(45 – 78%)(45 – 78%)
68
(52 – 83%)
0.610.61
Overall Overall SurvivalSurvival
18 mos (%)18 mos (%)
9090 8686 0.280.28
Progression-Progression-freefree
18 mos (%)18 mos (%)
7676 3636 0.0120.012
0 5 10 15
0.0
0.2
0.4
0.6
0.8
1.0
Time (years)
Pro
babi
lity
Progression free rateSurvival
Time (years)
Pro
babi
lity
of S
urvi
val 1.0
0.8
0.6
0.4
0.2
0.0
0 5 10 15
Progression Free Survival Progression Free Survival vs Overall Survivalvs Overall Survival
Progression Free Survival
Overall Survival
n=323
0 5 10 15
0.0
0.2
0.4
0.6
0.8
1.0
Time (years)
Pro
bab
ility
Incidence of progressionProbability of TRM death
Time (years)
Fai
lure
Rat
eCauses of Treatment FailureCauses of Treatment Failure
1.0 0.8
0.6
0.4
0.2
0.0
0 5 10 15
3 yr 5 yr 10 yr
Relapse 44% 46% 48%
TRM 6% 9% 15%
Competing Risks AnalysisCompeting Risks Analysis
3 yrs 10 yrs
Survival 68 % 39 %
Failure Free Rate 50 % 40 %
Probability of
2nd Cancer 5 % 12%
Leukemia 3 % 7 %
Solid Tumor 2 % 5 %
ASCT for ASCT for refractoryrefractory HL: HL:
Author n PFS, yrs OS, yrsSweetenham, 1999
175 32% 5y 36% 5y
Ferme, 2002 101 60% 5y 71% 5y
Moskowitz, 2004 75 49% 10y 48% 10y
Princess Margaret 2009
73 49% 3y 75% 3y
Princess Margaret Hospital Princess Margaret Hospital experience—refractory HLexperience—refractory HL• 157 patients referred for ASCT 1999-2006• Response rate to salvage therapy
– refractory (n=73): 49% vs relapsed (84): 83% (p<.0001)
• 3 y FF2TF – refractory 49% vs relapsed 67% (p=0.21)
• Overall survival– refractory 75% vs relapsed 91% (p=0.097)
Princess Margaret Hospital Princess Margaret Hospital experienceexperience
0 2 4 6
0.0
0.2
0.4
0.6
0.8
1.0
Time to death (years)
Su
rviv
al s
inc
e f
irs
t p
rog
res
sio
n
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| | | | | | |
| | | || | |
REF, n=73, 3y Survival=76%REL, n=84, 3y Survival=91%
Log-rank p-value=0.034
All patients, from time of treatment failure
Princess Margaret Hospital Princess Margaret Hospital experienceexperience
Patients undergoing ASCT, from time of transplant
0 1 2 3 4 5 6 7
0.0
0.2
0.4
0.6
0.8
1.0
Time to death (years)
PF
S s
ince
AS
CT
| |
|
|| |
||
|
||| | |
| | | || | ||| | | | | | | | | |
|
|
|
|| ||
| | | |||| | |
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| | | | | | | | |
REF, n=58, 3y PFS=49%REL, n=77, 3y PFS=67%
Log-rank p-value=0.21
Outline of this talkOutline of this talkOutline of this talkOutline of this talk
• prognostic factors following disease recurrence • role of local radiotherapy
• current results with ASCT
• strategies to improve ASCT outcome
• standard approaches – chemotherapy + rads
• second transplants- reduced intensity allogeneic SCT
Treatment Intensification before Treatment Intensification before ASCT:ASCT:
High-dose sequential therapyHigh-dose sequential therapy
DHAP x2
CRPR
PBSC collection
MTX 8 g/m2 Etoposide 2 g/m2
Cyclo 4 g/m2 + gcsf
BEAM ASCT
Josting et al Ann Oncol 2005
DHAP all relapsed refract.
n 102 85 17
CR (%) 21 24 12
PR (%) 66 68 53
fail (%) 13 8 35
Post ASCT
CR (%) 72 75 53
fail (%) 20 17 41
High-dose sequential therapy: High-dose sequential therapy: ResultsResults
GHSG-EBMT randomized trial
Hematologica 2009; 94[suppl.2]:204 abstract 0501Hematologica 2009; 94[suppl.2]:204 abstract 0501
DHAP x2
CRPR
R
BEAM ASCT
HDS: cyclo, MTX,etoposide
BEAM ASCTn=284 n=240
3y FFTF PFS OS HDS 67% 69% 83%Standard 71% 72% 84%
Tandem autotransplants for high risk relapsed/refractory HL
GELA/SFGM H96 trial
• 245 pts 1995-2002
• High risk: refractory or 2 risk factors (early relapse, stage 3 or 4, rel in radiation field) → tandem transplant
• Intermediate risk: single risk factor → single transplant
Improvement in outcome with Improvement in outcome with tandem transplant?tandem transplant?
Morschhauser, JCO 2008
Outline of this talkOutline of this talkOutline of this talkOutline of this talk
• prognostic factors following disease recurrence • role of local radiotherapy
• current results with ASCT
• strategies to improve ASCT outcome
• standard approaches – chemotherapy
• reduced intensity allogeneic SCT
Systemic Chemotherapy: Systemic Chemotherapy: Single Agent or Combination?Single Agent or Combination?
Systemic Chemotherapy: Systemic Chemotherapy: Single Agent or Combination?Single Agent or Combination?
vinca alkyloids 46-59% 6-8 m
gemcitabine 22-64% 6-9 m
gemcitabine –rituximab 61% 3 m
gemcitabine, vinorelbine,PEG-liposomal dox. 75% 8.5 m
Response rate vs. Disease controlRR (%) PFS (med)
Problem with Combination Therapy: MyelosuppressionProblem with Combination Therapy: MyelosuppressionProblem with Combination Therapy: MyelosuppressionProblem with Combination Therapy: Myelosuppression
MTD: (mg/m2)Gemcitabine 800 1000Vinorelbine 15 20Peg-liposomal-doxorubicin 10 15
Gr 4 neutropenia (%) 24 35Gr 3/4 platelets 43 14
treatment onschedule, full dose (%) 26 32
response rate (%) 75 61FS (median) 8.5 ---
Prior SCT No prior SCT(n = 37) (n = 43)
eg) GVD
Bartlett N, et al. Ann Onc, 2008
Outline of this talkOutline of this talkOutline of this talkOutline of this talk
• prognostic factors following disease recurrence • role of local radiotherapy
• current results with ASCT
• strategies to improve ASCT outcome
• standard approaches – chemotherapy
• reduced intensity allogeneic SCT
Allogeneic Stem Cell TransplantationAllogeneic Stem Cell TransplantationFollowing Relapse from ASCT for HLFollowing Relapse from ASCT for HL
Allogeneic Stem Cell TransplantationAllogeneic Stem Cell TransplantationFollowing Relapse from ASCT for HLFollowing Relapse from ASCT for HL
Pro• young patient population – going for cure• HL similar to other indolent B-cell lymphomas
- long survival after relapse- demonstrated GV–lymphoma effect in CLL,
follicular NHL
Con• published data from myeloablative alloSCT:
- high treatment-related mortality- GVHD, regimen-related
- little impact of GVHD on relapse rate
Myeloablative Allo Transplants After ASCTMyeloablative Allo Transplants After ASCT (IBMTR 1990-99)(IBMTR 1990-99)
Myeloablative Allo Transplants After ASCTMyeloablative Allo Transplants After ASCT (IBMTR 1990-99)(IBMTR 1990-99)
At 3 yrs:
• treatment related mortality 22% (16-31)
• relapse risk 52% (43-61)
• progression-free survival 25% (18-33)
- risk of treatmentrelated mortality higher forunrelated donors
Freytes, et al. Blood 2004
2 Gy TBI2 Gy TBI
Bu
Flu
Bu
Flu+ +
FluFlu
FluFlu CnICnIMelMel
ATG, -CD52 DLI
Reduced IntensityRegimens:
Recent Results with Reduced IntensityAllogeneic Transplantation for Relapsed HL
Peggs 49 44 5 16 (2 y) 32 (4y) 56 (4 y)
Sureda 89 55 85% ≥ 3 23 (1 y) 18 (3 y) 35 (3 y)
Alderlini 40 30 5 22 (18 m) 55 (18 m) 61 (18 m)
Armand 36 34 4 15 (3 y) 22 (3 y) 56 (3 y)
Alvarez 40 29 55% ≥ 3 25 (1 y) 32 (2 y) 48 (2 y)
Prior Prior regimens Tx-related
n ASCT (median) mortality PFS OS
Abbreviations: n: number of allogeneic transplants; ASCT autologous stem cell transplantlPFS: progression-free survival; OS: overall survival
1) Response to Donor Lymphocyte Infusion1) Response to Donor Lymphocyte Infusion1) Response to Donor Lymphocyte Infusion1) Response to Donor Lymphocyte Infusion
Armand 2008 13 NS 2/13 NS
Peggs 2005 16 3 9/16 5/16
Alderlini 2008 14 11 6/14 1/14
DLI after Relapse-Author n chemo Response Free
2)2) Decreased relapse, improved PFS withDecreased relapse, improved PFS with chronic GVHDchronic GVHD
spontaneous Sureda A, et al. JCO 2008
Armand P, et al. BBMT 2008
and after DLI Peggs KS, et al. Lancet 2005
2)2) Decreased relapse, improved PFS withDecreased relapse, improved PFS with chronic GVHDchronic GVHD
spontaneous Sureda A, et al. JCO 2008
Armand P, et al. BBMT 2008
and after DLI Peggs KS, et al. Lancet 2005
Is there a graft vs. HL effect after RIT? Is there a graft vs. HL effect after RIT?
ConclusionsConclusions
• Outcome of second-line therapy is determined by clinical factors, as much as by treatment– Not to mention biology…
• ASCT is the standard of care for all patients (suitable age, PS) with few exceptions– Late relapse, localized… think CMT
ConclusionsConclusions
• Novel agents are currently being tested that may be incorporated into primary or second line treatment– HDAC inhibitors, mTOR, antibody-chemo
conjugates…
• Reduced intensity transplants need to be evaluated in carefully conducted trials
RelapsedHL post-ASCT
Localized (stage I or IIA)
No prior RT
Localized (stage I or IIA)
No prior RT
Systemic recurrencestage III or IV
or relapse in priorradiation field
Systemic recurrencestage III or IV
or relapse in priorradiation field
Extended fieldradiation
Extended fieldradiation
RI allotransplant ifresponse to
chemotherapy
RI allotransplant ifresponse to
chemotherapy
≤ 6 mosfrom ASCT
≤ 6 mosfrom ASCT
≥ 6 mosFrom ASCT
≥ 6 mosFrom ASCT
Clinical trialof new agent
Clinical trialof new agent Young
good PS
Younggood PS
Single agentor combination chemotherapy
Single agentor combination chemotherapy
HLAmatched
donor
HLAmatched
donorClinical trialsof new agent
at progression
Clinical trialsof new agent
at progression
ASCT (if response,>5 yrs from
1st transplant)
ASCT (if response,>5 yrs from
1st transplant)
In summary:An algorithm
relapsedHL post-ASCT
Localized: (stage I,IIA)
no prior RT orrelapse out of field
systemic recurrencestage III or IV
or relapse in priorradiation field
extended fieldradiation
systemic recurrencestage III or IV
or relapse in priorradiation field
< 6 mosfrom ASCT
≥ 6 mosfrom ASCT
clinical trialof new agent
RIT ifresponse to
chemotherapy
≥ 6 mosfrom ASCT
younggood PS
single agentor combinationchemotherapy
HLAmatched
donor clinical trialsof new agent
at progression
ASCT (if response,>5 yrs from
1st transplant)
ConclusionsConclusions
• Numerous treatment options available– but cure is but cure is uncommonuncommon: take time to manage expectations, : take time to manage expectations,
discuss realistic goalsdiscuss realistic goals
• Disease control possible with radiation (sometimes) and chemotherapy (sometimes)– Keep it simple; reserve combinations for when transplant is
goal (chemosensitive)
• Exciting new agents entering or in clinical trials!– encourage patient, physician participation
• Allotransplant needs further study in well-designed phase II trials
Autologous Transplant at PMHAutologous Transplant at PMH• Salvage therapy to best response
mini-BEAM, GDP, DHAP
• Conditioning
etoposide 60 mg/kg Day -4
melphalan 160-180 mg/m2 Day -3
• Stem Cell Source
bone marrow – 46%
peripheral stem cells – 49%
• Post-transplant radiotherapy – 26%
Results – Patient CharacteristicsResults – Patient Characteristics
No. patients 323
ASCT 1986 – 1995 148
ASCT 1996 – 2005 175
Male 61 %
Age 33 yrs (16-67)
Histology
NS 73 %
Prior therapy
> 2 lines chemotherapy 11 %
radiotherapy 32 %
Results – Patient OutcomesResults – Patient Outcomes
Median follow-up 4.7 yrs (1-17)
Vital Status
Dead 47 % (154)
Disease Status
Relapse 45 % (146)
Outcome
Treatment Failure 53 % (170)
Second Cancer RiskSecond Cancer Risk
• Increases with every 10 year increment in age at time of transplant
Hazard Ratio
Second Cancer 1.9 (1.4-2.6)
Leukemia 1.9 (1.3-2.9)
Solid Tumour 1.8 (1.1-3.2)
0 2 4 6 8
0.0
0.2
0.4
0.6
0.8
1.0
ASCT in 1996 - 2005
Time (years)
Pro
bab
ility
Incidence of progressionProbability of TRM death
0 5 10 15
0.0
0.2
0.4
0.6
0.8
1.0
ASCT in 1986 - 1995
Time (years)
Pro
bab
ility
Incidence of progressionProbability of TRM death
ASCT 1986 – 1995
ASCT 1996 – 2005
0 5 10 15
0.8
0.6
0.4
0.2
0.0
0.8
0.6
0.4
0.2
0.0
0 2 4 6 8
Time (years)
Fai
lure
Rat
e
Identifying Prognostic Groups:Identifying Prognostic Groups:Multivariate Predictors of OutcomeMultivariate Predictors of Outcome
Identifying Prognostic Groups:Identifying Prognostic Groups:Multivariate Predictors of OutcomeMultivariate Predictors of Outcome
0 10 20 30 40 50 60
0.0
0.2
0.4
0.6
0.8
1.0
Progression Free Survival time (Months)
Pro
port
ion
Pro
gres
sion
Fre
e
Risk (Median PFS)
Low (14 m)Medium (6 m)High (4 m)
0 20 40 60 80 100
0.0
0.2
0.4
0.6
0.8
1.0
Overall Survival time (Months)P
ropo
rtio
n A
live
Risk (Median OS)
Low (36 m)Medium (21 m)High (9 m)
PFS:• >2 cycles salvage• extra-nodal sites at relapse
No risk factor : 14 m1 RF: 6 m2 RFs: 4 m
OS:• >2 cycles salvage• anemia at relapse
No risk factor : 36 m1 RF : 21 m2 RFs: 9 m
Al Farsi, et al, submitted
Time to Relapse after ASCT as a Time to Relapse after ASCT as a Predictor of Outcome/Guide to TherapyPredictor of Outcome/Guide to Therapy
• interval between ASCT and relapse is a strong predictor survival: recent series:
- Constans, et al, ASH 2004 (abstract 1649)
- Dean, et al, ASH 2007 (abstract 1903)
- Horning, et al ICML 2008 (abstract 118)
• median time to relapse 6-10 mos• outcome significantly worse
for pts with relapse <6-12 mos
from ASCT
0 20 40 60 80 100
0.0
0.2
0.4
0.6
0.8
1.0
Overall Survival time (Months)P
ropo
rtio
n A
live
Relapse 0-3 moRelapse 3-6 moRelapse 6-12 moRelapse >12 mo
Princess Margaret HospitalPrincess Margaret HospitalRadiation for Relapse Post-ASCTRadiation for Relapse Post-ASCT
39 pts: rads as first therapy
13 : extended field (mantle, inv Y)
26 : involved field (2: n = 5)
median PFS: 7 m OS: 41 m
vs. chemotherapy: PFS 6 m OS: 23 m
p = 0.18
Factors Associated with Outcome of Second Factors Associated with Outcome of Second SCT with Non-myeloablative ConditioningSCT with Non-myeloablative Conditioning
n = 147Prior auto: 135 (92%)Hodgkin lymphoma: 35 (24%)- response to chemo (CR/PR) : 20
refractory: 15
3 yr FFS 3 yr OS
HL 8%
35%
Mantle cell 57%
64%
Follicular 28%
31%
Barron, et al. J Clin Onc 2006
Reduced Intensity Allotransplant:Reduced Intensity Allotransplant:Superior to Standard RSuperior to Standard Rxx??
Cases: Phase II multicentre trial of RIT for HLin UK
Peggs, et al. Lancet 2005
Controls: - single institution (UCLH)- HL, relapsed post-ASCT- responded to next treatment- survived one yr post relapse
Thomson, et al. BMT 2008
Flu + Mel + alemtuzumab
Reduced Intensity Allotransplant:Reduced Intensity Allotransplant:Superior to Standard RSuperior to Standard Rxx??
Outcome:
Overall survival - 5 yr from ASCT: Standard Rx 15% RIT 65%
RIT
no RIT
Thomson, et al. BMT 2008