Optimizing High Dose Therapy
Results from MRC Myeloma IX randomized trial
G.J. Morgan1, F.E. Davies1, W.M. Gregory2, S.E. Bell2, A.J. Szubert2, N. Navarro Coy2,
M.T. Drayson3, R.G. Owen4, G. Cook4, F.M. Ross5, N.H. Russel,5 S. Feyler,6 P.R.E.
Johnson,7 G.H. Jackson8, J.A. Child2
1Institute of Cancer Research, Royal Marsden Hospital, London;2University of Leeds, Leeds;
3University of Birmingham, Birmingham; 4St James' University Hospital, Leeds; 5Wessex Regional
Genetics Laboratory, University of Southampton, Salisbury; 6Royal Devon and Exeter Hospital,
Exeter, UK; 7Department of Haematology, Western General Hospital, Edinburgh, UK 8University of
Newcastle, Newcastle-upon-Tyne; UK
What is role of High Dose Therapy in NDMM?
· Younger patients show the most significantly reduced life
expectancy and most potential for improved outcomes.
· HDT is the treatment associated with the best outcomes in
MM.
· How can these outcomes be improved further with the use of
"novel" agents?
· We have assessed comprehensively how HDT performs
currently.
· Having defined the current best strategy, we can ask how can
this be improved.
2
HDT, high dose therapy; NDMM, newly diagnosed multiple myeloma.
1

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MRC Myeloma IX study ­ factorial design
Bisphosphonate
Induction
Maintenance
treatment
CTDa
ation
Older,
less fit
ZOL
MP
Thalidomide
Randomiz
maintenance
ation
ation
CTD
No
CLO
(n = 556)
maintenance
Randomiz
ation
Randomiz
Young,
HDM
more fit
200 mg/m2
CVAD
(N = 1,111)
(n = 555)
Randomiz
CLO, sodium clodronate; CTD, cyclophosphamide + thalidomide + dexamethasone; CTDa, CTD
attenuated (low-intensity); CVAD, vincristine + doxorubicin + dexamethasone + cyclophosphamide;
Morgan GJ, et al. Lancet 2010; 376: 1989­99.
HDM, high-dose melphalan; MP, melphalan + prednisone; OS, overall survival;
Morgan GJ, et al. Lancet Oncol. 2011;in press.
PFS, progression-free survival; SRE, skeletal-related event; ZOL, zoledronic acid.
Morgan GJ, et al. Haematologica 2011;in press.
Maximizing response pre- and
post-HDT is a therapeutic aim.
What is the optimal induction strategy?
Hypothesis 1.
CTD not inferior to CVAD
(OS and PFS)
4
2

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MRC Myeloma IX HDT pathway:
baseline patient characteristics
Characteristic
CVAD
CTD
(n = 556)
(n = 555)
Female sex, n (%)
208 (37.4)
211 (38)
Median age, years (range)
59 (31­74)
59 (33­78)
ISS stage at initial randomization, n (%)
I
124 (22.3)
151 (27.2)
II
191 (34.4)
189 (34.1)
III
183 (32.9)
160 (28.8)
Missing data
58 (10.4)
55 (9.9)
Median 2-microglobulin, mg/L (range)
4.1 (0.1­66.0)
3.9 (0.1­114.0)
ISS, International Staging System.
Impact of age on OS in patients receiving HDT
100
80
)
(% 60
40
Patients
55 years (n = 379)
56-64 years (n = 517)
20
> 64 years (n = 215)
P < .001
0
12
24
36
48
60
72
84
OS (months)
55 years
379
344
316
225
130
42
6
56-64 years
517
441
387
261
154
61
1
> 64 years
215
178
159
99
52
21
0
·
HDT is safe even in patients older than 64 years, although there are
significant differences in survival according to age group.
3

---

Characteristic of transplant group (1)
· A total of 749 (67%) underwent transplantation (median age 58
years).
The median age of patients not undergoing transplantation was 61 years
Taking into account age, the outcome for these patients was the same
as those in the non-intensive pathway
· A small proportion of patients (17/1,111 [1.5%]) over the age of
70 were included in the study.
9 patients were randomised to receive CTD induction and 8 were
randomised to CVAD induction
Only 3 patients (CTD: 2 patients; CVAD: 1 patient) received subsequent
HDT
7
Characteristic of transplant group (2)
· Taking early mortality of 8.5% we show that there was no
difference between the arms in favour of CTD:
CVAD, 52/556 (9.4%) and CTD, 41/555 (7.4%) (p = 0.28 Fisher's exact
test)
· During HDT and the peritransplant period a transplant-related
mortality rate of 1.5% was seen that was independent of the
induction pathway followed:
CVAD, 6/379 (1.6%) vs CTD 5/370 (1.4%; p = 1.0, Fisher's exact test)
· An improvement in CR rate was noted after ASCT in both arms
of the study:
30.5% increase in CR rate in the CVAD arm and 39.1% in the CTD arm
8
CR, complete response.
4

---

Response rates
After induction therapy
After HDT with ASCT
Response, %
CVAD
CTD
p*
CVAD
CTD
P*
(n = 556)
(n = 555)
(n = 379)
(n = 370)
Overall response
71.2
82.5
< 0.0001
90.0
91.6
0.45
CR
10.4
16.0
0.0061
40.9
55.1
0.0001
VGPR
17.1
27.2
< 0.0001
21.4
18.6
0.36
PR
43.7
39.3
0.14
27.7
17.8
0.0017
Minimal response
7.6
3.2
0.0020
1.8
0.5
0.18
No change
6.5
2.5
0.0021
1.8
0.8
0.34
Disease progression
2.7
3.2
0.60
2.4
3.2
0.51
Early death
4.1§
2.2§
0.085
0.8¶
1.6¶
0.34
Unable to determine
7.9
6.3
0.35
3.2
2.2
0.50
* Fisher exact test; Logistic regression; §Within 60 days of randomization; ¶Within 100 days of high-dose therapy date.
· CTD is associated with higher ORR rates post-induction.

The quality of response improves significantly post-ASCT
ASCT, autologous stem-cell transplantation; ORR, overall response rate; PR, partial response; VGPR, very good partial response.
Response rates following induction with novel
agent-containing regimens and post-transplantation
VGPR (%)
Post-induction
Post-transplant
87
69
74
66
59
54
62
37
38
37
41
31
43
15
VAD
VD
TAD
PAD
VTD
TD
CTD
Induction regimens of interest not shown: CVD, RVD, RD and Rd.
·
Exact comparisons with current alternative drug combination require formal
randomized studies.
Harousseau JL, et al. J Clin Oncol. 2010; 28:4621-29.
Rajkumar V, et al. Lancet Oncol. 2010;11:29-37.
CVD, cyclophosphamide + bortezomib + dexamethasone; PAD, bortezomib + doxorubicin + dexamethasone;
Lokhorst H, et al. Blood. 2010;115:1113-20.
Rd, lenalidomide + low-dose dexamethasone; RD, lenalidomide + high-dose dexamethasone;
Sonneveld P, et al. Blood. 2008;112:abstract 653.
RVD, lenalidomide + bortezomib + dexamethasone; TAD, thalidomide + doxorubicin + dexamethasone;
Cavo M, et al. Lancet. 2010;376:2075-85.
TD, thalidomide + dexamethasone; VAD, vincristine + doxorubicin + dexamethasone;
Kumar S, et al. Blood. 2010;116:abstract 621.
VD, bortezomib + dexamethasone; VTD, bortezomib + thalidomide + dexamethasone.
Richardson PG, et al. Blood. 2010;116:679-86.
5

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Impact of induction therapy on PFS and OS
Median PFS (95%, CI):
Median OS (95%, CI):
CTD, 27 (24-29) vs. CVAD, 25 (23-26) months
CTD, NR (61-NR) vs. CVAD, 63 (59-NR) months
100
100
80
80
) 60
)
60
(%
(%
40
40
CTD
CTD
Patients 20
CVAD
Patients
20
CVAD
P = 0.56
P = 0.29
0
0
CTD 553
428
298
149
68
23
1
CTD
553
484
440
301
168
62
3
CVAD 540
405
273
152
82
31
0
CVAD
540
468
412
282
167
61
1
012
24
36
48
60
72
012
24
36
48
60
72
PFS (months)
OS (months)
·
Median follow-up ­ 47 months.
·
CTD is non-inferior to CVAD for PFS and OS.

OS benefit emerging after 2 years
Impact of CR/response status on survival
outcomes
100
100
80
CTD
80
CVAD
)
)
60
P = 0.10
(% 60
(%
CR
< CR
40
40
Patients
P = 0.0003
Patients
20
20
0
CR 359
352
274
150
79
27
1
CR
344
344
324
230
134
51
3
< CR 340
326
215
104
55
21
0
< CR
355
352
325
222
140
50
1
0
12
2436
4860
72
012
24
36
48
60
72
PFS (months)
OS (months)
· PFS is greater in patients with a CR, regardless of treatment.
· There is a trend for OS with CTD in responding patients.
· With prolonged follow-up, the improvement in CR rates observed in the CTD
arm translates to longer OS (3% improvement at 9 years).
6

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MRC Myeloma IX HDT pathway:
iFISH at presentation
Prevalence
Cytogenetics
CVAD
CTD
Total
(n = 556)
(n = 555)
Adverse iFISH, n/N (%)
141/307 (46)
152/319 (48)
293/626 (47)
gain 1q21
98/267 (37)
101/264 (38)
199/531 (37)
t(4;14)
35/305 (11)
41/314 (13)
76/619 (12)
del1p32.1
24/254 (9)
29/256 (11)
53/510 (10)
17p-
20/292 (7)
26/299 (9)
46/591 (8)
t(14;16)
12/300 (4)
7/312 (2)
19/612 (3)
t(14;20)
4/301 (1)
7/311 (2)
11/612 (2)
Favourable iFISH, n/N (%)
166/307 (54)
167/319 (52)
333/626 (53)
del13q
128/299 (43)
156/317 (49)
284/616 (46)
t(11;14)
46/304 (15)
46/313 (15)
92/617 (15)
del22q
30/250 (12)
26/242 (11)
56/492 (11)
t(6;14)
3/299 (1)
2/307 (1)
5/606 (1)
iFISH, interphase FISH.
Boyd KD, et al. Leukemia. In press 2011.
Impact of cytogenetics on survival in patients
with a CR following induction therapy
100
100
80
80
)
)
60
(%
(% 60
40
Favourable
40
Favourable
20
Adverse
Adverse
Patients
Patients 20
P < 0.0001
P < 0.0001
0
0
Favourable 112
111
95
64
36
11
1 Favourable 112
112
110
86
53
22
2
Adverse 85
82
49
19
9
5
0
Adverse 85
85
75
54
32
11
1
0
12
2436
4860
72
012
24
36
48
60
72
PFS (months)
OS (months)
·
Among patients who achieved CR, adverse iFISH remains a predictor of
poor PFS and OS.
7

---

Impact of induction therapy on PFS in
favourable and adverse iFISH
Favourable iFISH
Favourable iFISH
100
AB 100
)
80
)
80
(%
60
(%
60
CTD
ts
CTD
ts
n
40
n
CVAD
e
40
CVAD
e
ti
ti
P = 0.11
a
20
a
P = 0.90
20
P
P
0
0
CTD 167 136
105
58
24
8
1
CTD 167 153 150 105
57
27
2
CVAD 166 127
96
59
36
14
0
CVAD 166 143 134 104
66
29
0
0
1224
36
4860
72
012
24
36
48
60
72
PFS (months)
OS (months)
100
CD 100
Adverse iFISH
Adverse iFISH
80
)
80
)
(%
60
(%
60
ts
ts
n
40
n
40
CTD
e
CTD
e
ti
ti
CVAD
a
20
CVAD
a
20
P
P = 0.75
P
P = 0.85
0
0
CTD 152 111
58
21
11
5
CTD 152 127 106
74
44
12
1
CVAD 141 102
51
21
13
7
CVAD 141 121
99
63
38
13
0
0
12
24
364860
72
012
24
36
48
60
72
PFS (months)
OS (months)
·
In patients with favourable iFISH receiving CTD induction, there is a trend
for an emerging survival benefit compared with CVAD.
·
This effect is not seen in patients with adverse iFISH.
Myeloma XI
Can response and outcome be improved by using a
"sequential approach"
CTD
vs
CRD
Assess response
<VGPR
CR
nothing
vs
CVD
Endpoints
response rates (pre and post transplant),
PFS, OS, impact by genetic risk status.
16
8

---

Maintenance of responses is an
approach that can improve outcomes
Hypothesis 2.
Thalidomide maintenance superior to
no maintenance (OS)
17
MRC Myeloma IX study ­ factorial design
Bisphosphonate
Induction
Maintenance
treatment
CTDa
ation
Older,
less fit
ZOL
MP
Thalidomide
Randomiz
maintenance
ation
ation
CTD
No
CLO
(n = 556)
maintenance
Randomiz
ation
Randomiz
Young,
HDM
more fit
200 mg/m2
CVAD
(N = 1,111)
(n = 555)
Randomiz
Morgan GJ, et al. Lancet 2010; 376: 1989­99.
Morgan GJ, et al. Lancet Oncol. 2011;in press.
Morgan GJ, et al. Haematologica 2011;in press.
9

---

Baseline characteristics at maintenance
randomization
Maintenance
No maintenance
(N = 408)
(N = 410)
Median time between initial and maintenance
8.3 (3.5­21.7)
8.2 (3.9­18.6)
randomization, months (range)
Randomized induction chemotherapy regimen, n (%)
CVAD
121 (29.7)
120 (29.3)
CTD
124 (30.4)
127 (31.0)
MP
79 (19.4)
82 (20.0)
CTDa
84 (20.6)
81 (19.8)
Response at maintenance randomization*, n (%)
CR
158 (38.7)
139 (33.9)
VGPR
65 (15.9)
79 (19.3)
PR
125 (30.6)
119 (29.0)
Minimal response
17 (4.2)
23 (5.6)
No change
10 (2.5)
24 (5.9)
Progressive disease
9 (2.2)
14 (3.4)
Missing data
24 (5.9)
12 (2.9)
*After induction/high-dose therapy and therefore preceding maintenance randomization.
PFS and OS according to maintenance
randomization
Median follow-up from maintenance randomization: 38 months (range, 12­66)
100
100
Maintenance, N = 407
No maintenance, N = 410
80
80
HR [95% CI] = 1.45 [1.22, 1.73],
P = 0.0003
)
)
60
(%
60
(%
40
40
Patients
Maintenance, N = 408
Patients
No maintenance, N = 410
20
20
HR [95% CI] = 0.91 [0.72, 1.17],
P = 0.40
0
12
24
36
48
60
72
0
12
24
36
48
60
72
PFS (months)
OS (months)
·
Thalidomide maintenance improves PFS but no OS benefit could be
demonstrated.
CI, confidence interval; HR, hazard ratio.
10

---

PFS and OS according to maintenance
randomization: favourable iFISH
100
100
Maintenance, N = 125
No maintenance, N = 129
80
P = 0.004
80
)
)
(%
60
60
(%
40
40
Patients
Patients
Maintenance, N = 126
No maintenance, N = 129
20
20
P = 0.60
0
12
24
36
48
60
72
0
12
24
36
48
60
72
PFS (months)
OS (months)
·
Among patients with favourable iFISH, thalidomide maintenance
significantly prolongs PFS with emergent OS benefit.
PFS and OS according to maintenance
randomization: adverse iFISH
100
100
Maintenance, N = 99
No maintenance, N = 98
80
80
P = 0.48
)
)
60
60
(%
(%
40
40
Patients
Patients
Maintenance, N = 99
No maintenance, N = 98
20
20
P = 0.009
0
12
24
36
48
60
72
0
12
24
36
48
60
72
PFS (months)
OS (months)
· Among patients with adverse iFISH, thalidomide maintenance had no effect
on PFS and adverse effect on OS.
11

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Impact of induction and maintenance on
outcome following HDT
CVAD + Maintenance
100
CVAD + No maintenance
100
CTD + Maintenance
80
CTD + No maintenance
80
)
)
60
(%
60
(%
CVAD + Maintenance
CVAD + No maintenance
40
40
Patients
CTD + Maintenance
Patients
CTD + No maintenance
20
20
Logrank P = 0.0261
Logrank P = 0.6885
0
0
010
20
30
40
50
60
70
0
1020
30
4050
60
70
PFS (months)
OS (months)
·
Thalidomide maintenance prolongs PFS regardless of induction treatment.
·
Consistent with overall study results.
Meta-analysis of all studies including a
thalidomide maintenance arm
Number of
P-value for
Study
patients
Odds ratio (Cl)*
interaction
IFM-9902 1
597
0.61 (0.33­1.13)
0.040
Spencer A, et al.2
243
0.43 (0.21­0.91)
0.004
Lokhorst HM, et al.3
556
0.96 (0.68­1.35)
0.770
Total Therapy 2 4
668
0.82 (0.60­1.12)
0.090
Ludwig H, et al.5
289
1.32 (0.47­3.71)
0.490
Myeloma IX
820
0.77 (0.55­1.07)
0.040
Assuming effective
salvage therapy
All studies
3,173
0.80 (0.70­0.91)
0.001
0
0.5
1
1.5
2
Favours
Favours
maintenance
no maintenance
*Odds ratios are with 99% Cls for all but the total, which is 95% Cl.
·
Thalidomide maintenance offers an OS advantage.
1. Attal M, et al. Blood. 2006;108:3289-94.
2. Spencer A, et al. J Clin Oncol. 2009;27:1788-93. 3. Lockhorst HM, et al. Blood. 2010;115:1113-20.
4. Barlogie B, et al. Blood. 2009;112:3115-21. 5. Ludwig H, et al. Blood. 2009;113:3435-42.
12

---

Composite OS curve in a pooled analysis of
thalidomide maintenance studies
100
Maintenance, N = 1,367
No maintenance, N = 1,605
80
P = 0.001
)
(%
60
40
OS curves adjusted for study/group1
Patients
Differences:
3 years: 2.5% (95% CI -0.7%­5.6%)
20
5 years: 5.8% (95% CI 1.2%­10.4%)
7 years: 11.8% (95% CI 5.6%­18.0%)
0
12
24
36
48
60
72
84
96
118
OS (months)
Numbers at risk
Maintenance 1,367 1,246 1,023 786 503
298 168
88
48
12
No maintenance 1,605 1,451 1,235 903 472
248 139
88
46
9
·
Thalidomide maintenance offers a significant OS benefit across trials.
1. Gregory WM. Br J Cancer 1988; 58:202-4.
Lenalidomide maintenance significantly
improves PFS
IFM 2005-022
MM-0151
CALGB 1001043
Maintenance Therapy
Maintenance Therapy
NDMM/Continuous Therapy
Post-SCT
Post-SCT
001.
75
42 mos
0.
050.
24 mos
520.
000.
0
6
12
18
24
30
36
42
Placebo
Revlimid
HR 0.40, P < 0.001
HR 0.50, P < 0.0001
HR 0.40, P < 0.0001
1. Palumbo A, et al. Blood. 2010; 116: Abstract 622
2. Attal M, et al. Blood. 2010; 116: Abstract 310
SCT, stem-cell transplantation
3. McCarthy P, et al. Blood; 2010; 116: Abstract 37
13

---

How can lenalidomide maintenance be
improved further?
No
maintenance
Vorinostat characteristics
·
Inhibits IL6
Lenalidomide
·
Turns on tumour-suppressor genes
Randomization
maintenance
·
Inhibits HSP90
·
Ideal companion for lenalidomide
Lenalidomide
Vorinostat
maintenance
27
Targeting bone is important to reduce
SRE and may improve survival
Hypothesis 3.
ZOL superior to CLO
(improve survival, reduction in SREs)
28
14

---

Relative risk of SREs by treatment*
Risk
reduction
P value
Overall (N = 1,960)
0.74
ZOL vs CLO
26%
0.0004
Intensive (n = 1,111)
1.03
CTD vs CVAD
0%
0.80
0.76
ZOL vs CLO
24%
0.017
00.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Hazard ratio
Favours ZOL, C-TDa, CTD
Favours CLO, MP, CVAD
* SREs were defined as vertebral fractures, other fractures, spinal cord compression, and the requirement of radiation or surgery for bone lesions
or the appearance of new osteolytic bone lesions.
·
ZOL treatment significantly reduces the risk of SREs compared with CLO.
Morgan G, et al. Blood; 2010; 116: abstract 311.
Conclusions (1)
· CTD should be considered a standard induction therapy for
patients with NDMM undergoing HDT/ASCT.
Significant difference in CR rates maintained post-HDT (p = 0.0001)
This effect is independent of bias introduced by investigator assessment as the
response was predominantly assessed centrally
This observation illustrates the importance of high-dose melphalan in improving
response rates even when the induction is given to maximum effect
Patients with a CR who had favourable iFISH show the greatest
benefit
After 2 years there is an emerging OS benefit with CTD
· ZOL decreases the SREs vs CLO in both study arms.
· This large data set analysis shows that CTD is an alternative
option to current triplet drug combinations such as VTD, PAD,
and CVD.
15

---

Conclusions (2)
· Thalidomide maintenance therapy improves PFS
significantly without a significant survival benefit.
With effective treatment at progression, thalidomide maintenance
results in improved OS
Patients with favourable iFISH benefit the most from maintenance
treatment
· The clinical impact would be improved if patients could
remain on maintenance therapy for longer.
· The use of novel agents as maintenance is important.
·
Is this relevant for all patients?
·
Subsequent analysis will aim to identify the optimal sequence of
agents to use
Acknowledgements
Chief Investigators
University of
HMDS, Leeds
MRC Leukaemia Trial Steering
JA Child
Birmingham
RG Owen
Committee
GJ Morgan
MT Drayson
AC Rawstron
MRC Leukaemia Data Monitoring
GH Jackson
K Walker
R de Tute
and Ethics Committee
A Adkins
M Dewar
NCRI Haematological Oncology
N Newnham
CTRU, Leeds
S Denman
Clinical Studies Group
K Cocks
NIHR, through the National Cancer
Wessex Regional
W Gregory
ICR, London
Research Network
Genetics Laboratory,
A Szubert
FE Davies
Salisbury
UK Myeloma Forum Clinical Trials
S Bell
F Ross
M Jenner
Committee
N Navarro Coy
L Chieccio
B Walker
F Heatley
D Johnson
Myeloma UK
P Best
LTHT, Leeds
D Gonzalez
Funding
J Carder
G Cook
N Dickens
Medical Research Council
M Matouk
S Feyler
K Boyd
Pharmion
D Emsell
D Bowen
P Leone
Novartis
A Davies
L Brito
Chugai Pharma
D Phillips
A Avridromou
Bayer Schering Pharma
A Gillman
OrthoBiotech
L Flanagan
Celgene
C Tyas and others
Kay Kendall Leukaemia Fund
16

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Acknowledgements
Patients and staff from 121 participating institutions in the UK
Nottingham City Hospital
Western General Hospital, Edinburgh
Royal Devon and Exeter Hospital
Leeds General Infirmary
Birmingham Heartlands Hospital
Royal Hallamshire Hospital, Sheffield
Hull Royal Infirmary
Royal Liverpool University Hospital
Mid Yorkshire NHS Trust
Ninewells Hospital, Dundee
University Hospital of Wales, Cardiff
Torbay Hospital, Torquay
Addenbrooke's Hospital, Cambridge
Aberdeen Royal Infirmary
Worcester Royal Infirmary
St James's University Hospital, Leeds
Russells Hall Hospital, Dudley
Derbyshire Royal Infirmary
Christie Hospital, Manchester
Royal Cornwall Hospital, Truro
Southampton General Hospital
Blackpool Victoria Hospital
James Cook University Hospital
Colchester General Hospital
Glan Clwyd Hospital
Medway Maritime Hospital, Gillingham
Norfolk and Norwich University Hospital
James Paget Hospital, Great Yarmouth
Royal United Hospital, Bath
St Helier Hospital, Carshalton
The Great Western Hospital, Swindon
Gloucestershire Royal Hospital
Singleton Hospital, Swansea
New Cross Hospital, Wolverhampton
Ysbyty Gwynedd, Bangor
Monklands General Hospital, Airdrie
Eastbourne District General Hospital
Sandwell General Hospital
Wycombe General Hospital
Hillingdon Hospital, Uxbridge
Lincoln County Hospital
Chesterfield & N Derbyshire Royal
Kings Mill Hospital, Sutton-in-Ashfield
Queen Elizabeth Hospital, Kings Lynn
Kent and Canterbury Hospital
University Hospital Aintree, Liverpool
St Bartholomew's Hospital, London
Cheltenham General Hospital
Western Infirmary, Glasgow
Southern General Hospital, Glasgow
Hereford County Hospital
Glasgow Royal Infirmary
Darent Valley Hospital
Salisbury District Hospital
Stepping Hill Hospital, Stockport
Trafford General Hospital, Manchester
Bristol Haematology & Oncology Centre
Good Hope Hospital, Sutton Coldfield
St Richard's Hospital, Chichester
Oldchurch Hospital, Romford
Darlington Memorial Hospital
Pembury Hospital
Taunton and Somerset Hospital
Diana Princess of Wales Hospital, Grimsby
Warwick Hospital
Walsgrave Hospital
Bradford Royal Infirmary
Southend General Hospital
The Royal Bournemouth Hospital
Manchester Royal Infirmary
Whiston Hospital, Prescot
Derriford Hospital
Stoke Mandevil e Hospital, Aylesbury
Queen Elizabeth Hospital, Gateshead
Worthing Hospital
Scarborough General Hospital
Countess of Chester Hospital
Royal Victoria Infirmary, Newcastle
Hope Hospital, Manchester
Victoria Infirmary, Glasgow
Rotherham General Hospital
Poole Hospital
Princess Royal University Hospital
Milton Keynes General Hospital
Barnsley District Hospital
North Devon District Hospital
Kingston Hospital
Royal Alexandra Hospital, Paisley
Borders General Hospital
Queen Elizabeth Hospital, Birmingham
City Hospital, Birmingham
King George Hospital, Ilford
Conquest Hospital, St Leonard's on Sea
Pilgrim Hospital, Boston
Dorset County Hospital
Southmead Hospital, Bristol
Royal Surrey County Hospital
University Hospital of North Tees
George Eliot Hospital
Southport and Formby District General Hospital
North Tyneside General Hospital
Epsom General Hospital
Grantham and District Hospital
Harrogate District Hospital
Basildon Hospital
Doncaster Royal Infirmary
Royal Marsden Hospital, Sutton
Nevill Hall Hospital, Abergavenny
Queen Mary's Hospital, Sidcup
Prince Charles Hospital, Merthyr Tydfil
Prince Philip Hospital
Royal Bolton Hospital
Central Middlesex Hospital
Northwick Park Hospital, Harrow
Arrowe Park Hospital
Ipswich Hospital
South Tyneside District Hospital
Mid Staffordshire General Hospital
Mayday Hospital
Forth Valley
West Suffolk Hospitals NHS Trust
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