Overview of Mayo Clinic Cancer Center

Report
Arizona, USA
What should you expect of your MPN Therapy?
Ruben A. Mesa, MD
Professor & Chairman, Division of Hematology & Medical Oncology
Deputy Director, Mayo Clinic Cancer Center
Mayo Clinic – Arizona, USA
©2011 MFMER | 3133089-1
What should you expect of your MPN Therapy?
Individualizing Therapy
• What is the spectrum of disease burden and
risk in MPNs?
• What are expectations of therapy?
• Current and evolving treatment options for MPN
patients
©2011 MFMER | 3133089-2
Burden of ET/PV
Macrovascular
Risk
Et & PV
Associated
Symptoms
Microvascular
Symptoms
MF
MPN
Associated
Associate
Symptoms
d
Splenomegaly
Symptom
s
Anemia/
Cytopenis
Burden of Myelofibrosis
Evolution of MPN Symptom Assessment
Tools
Vascular and Ψ Sx
9 Items
Constitutional Sx
5 Items
Spleen Sx
4 Items
Brief Fatigue
Inventory
(BFI) – 9 Items
QOL 1 Item
MPN-SAF Languages
• English
• French
• German
MF–SAF
• Spanish
• Dutch 2009
(19 items)
• Swedish
• Italian
• Portuguese
MF-SAF 2.0
• Mandarin
(7 items 2011)
• Japanese
JCO in Press
• Hebrew
MPN–SAF
2011
(27 items)
Blood 2011
MPN-SAF TSS
(10 items 2012)
JCO 2012
MPN Symptom Burden by Quartiles
1858 MPN-SAF Respondents
Q1
TSS <8
Q2
TSS 8 -17
Parameter
Age
Q3
TSS 18 - 31
P value of Comparison
0.24
Gender F>M
<0.001
MPN Diagnosis
<0.001
Subtype of MF
0.86
IPSET (ET Risk)
0.18
PV Risk (PV)
0.30
DIPSS (MF Risk)
Quartile 1 (Q1): 0-24%
Quartile 3 (Q3): 50-74%
100%
Q4
TSS >32
<0.001
Quartile 2 (Q2): 25-49%
Quartile 4 (Q4): 75-
ET (N=775)
Q1 – 30%
Q2 – 26%
Q3 – 24%
Q4 – 20%
PV (N=654)
Q1 – 25%
Q2 – 23%
Q3 – 26%
Q4 – 26%
MF (N=423)
Q1 – 17%
Q2 – 21%
Q3 – 26%
Q4 – 36%
MPN Symptom Burden by Quartiles
Comparison between MPN Diagnosis and Quartiles
Q4 (TSS > 32)
P<0.001
Q3 (TSS: 18-31)
MF (N=423)
PV (N=654)
ET (N=775)
Q2 (TSS: 8-17)
Q1 (TSS<8)
0%
10%
20%
30%
40%
EORTC QLQ-C30 Scores in MF and Other
Hematologic Malignancies and Solid Tumors
EORTC QLQ-C30
Global Health Status/QoL
Myelofibrosis
COMFORT-I
placebo arm Myelofibrosis
(N=147*)
(N=96)1
CML
(N=73)2
Myeloma
(N=944)3
Breast
(N=2782)3
Lung
(N=3332)3
Recurrent/
metastatic
cancers
(N=4812)3
52.9
59.9
70.2
55.7
61.8
56.6
56.3
Physical Functioning
67.2
74.9
78.0
67.7
78.4
71.9
75.8
Role Functioning
63.2
68.8
78.1
60.1
70.9
61.5
60.7
Emotional Functioning
75.5
76.5
78.8
71.3
68.6
68.9
68.7
Cognitive Functioning
80.1
77.0
86.1
78.1
81.5
82.3
80.5
Social Functioning
66.1
74.9
84.3
63.2
77.0
71.3
70.5
Fatigue
54.1
41.0
29.8
48.7
33.3
41.1
41.8
Pain
29.9
22.6
10.1
47.1
28.7
29.7
33.7
Dyspnea
37.0
29.8
15.5
26
18.1
37.9
23.4
Insomnia
39.1
33.7
26.9
28.9
29.8
31.6
33.6
Appetite loss
33.3
15.1
13.7
23.2
18.5
28.1
28.2
Functional Subscales
Symptom Scales/Single
Items
= Worsening Direction
Quality of Life
What is quality of life
?
Increasing
Definitions
HRQOL in MPNs?
Σ
•
•
•
•
MPN related symptoms
Medication related toxicities
Problems from prior MPN complications
Stressors from having their MPN
• Financial
• Emotional
• Intrapersonal
• Co-morbidities
• Hassle of medical care
What should you expect of your MPN Therapy?
Individualizing Therapy
• What is the spectrum of disease burden and
risk in MPNs?
• What are expectations of therapy?
• Current and evolving treatment options for MPN
patients
©2011 MFMER | 3133089-11
Evolving MPN Prognostic Scales
IPSET
(ET – 3 groups)
Survival
Thrombosis Risk
Age
Leukocytes
PV
Risk (4 groups)
Survival
Leukemia Rates
DIPSS
(PMF – 4 groups)
Survival
≥ 60 (2pts) vs. < 60
≥70 (3pts)
60-69 (2pts), <60
≥65 (1pt) vs. <65
≥ 11 (1pt) vs.
< 11 x 109/L
≥15 (1 point) vs.
<15 x 109/L
>25 (1pt) vs.
≤25 x 109/L
Hemoglobin
<10 (2 pts) vs.
≥10g/dL
Present# (1pt) vs. Absent
Constitutional
Symptoms
≥1% (1pt) vs. <1%
Blasts
Prior
Thrombosis
Yes (1 point) vs. No
Risk Group
Point Cutoffs
0; 1-2; 3-4 pts.
Passamonti
Blood 2012
0; 1-2; 3; 4 pts.
Tefferi
ASH 2011
0; 1-2; 3-4; ≥4 pts.
Passamonti
Blood 2010
# = >10% Weight Loss over prior 6 months, Night Sweats, Unexplained Fever
New Response Criteria for MPNs
ET2
PV2
MF1
Complete response



Partial response



Clinical improvement

Stable disease

No response



Relapse
Other responses
Molecular Molecular
Cytogenetic and
molecular
1. Tefferi A et al. Blood. 2013;122:1395-1398. 2. Barosi G et al. Blood. 2013;121:4778-4781.
New Response Criteria for MF: Complete Response1
Required criteria: for all response categories, benefit must last for ≥12 wks
to qualify as a response
Bone marrow:
Age-adjusted normocellularity;
<5% blasts;
≤Grade 1 MF; and
Peripheral blood:
Hemoglobin ≥ 100 g/L and <UNL;
Neutrophils ≥ 1 x 109/L and <UNL;
Platelets ≥ 100 x 109/L and <UNL;
<2% immature myeloid cells; and
Clinical:
Resolution of disease symptoms
Spleen and liver not palpable
No evidence of EMH
EMH: extramedullary hematopoiesis
1. Tefferi A et al. Blood. 2013;122:1395-1398.
New Response Criteria for MF: Partial Response1
Peripheral blood:
Hemoglobin ≥ 100 g/L and <UNL;
Neutrophils ≥ 1 x 109/L and <UNL;
Platelets ≥ 100 x 109/L and <UNL;
<2% immature myeloid cells
and
Clinical:
Resolution of disease symptoms;
spleen and liver not palpable; no
evidence of EMH
1. Tefferi A et al. Blood. 2013;122:1395-1398.
Bone marrow:
Age-adjusted normocellularity;
<5% blasts; ≤grade 1 MF, and
or
Peripheral blood:
Hemoglobin ≥ 85 but <100 g/L and
<UNL;
Neutrophils ≥1 x 109/L and <UNL;
Platelets ≥50, but <100 x 109/L and
<UNL;
<2% immature myeloid cells and
Clinical:
Resolution of disease symptoms;
spleen and liver not palpable; no
evidence of EMH
New Response Criteria for MF: Other Categories1
Clinical
improvement
Anemia
response
Achievement of anemia, spleen, or symptoms response
without progressive disease or increase in severity of
anemia, thrombocytopenia, or neutropenia
Transfusion-independent pts: a ≥20 g/L increase in Hb level
Transfusion-dependent pts: becoming transfusion
independent
Baseline splenomegaly that is palpable at 5-10 cm, below
the LCM, becomes not palpable, OR
Spleen
response
Baseline splenomegaly that is palpable at >10 cm, below
the LCM, decreases by ≥50%
Baseline splenomegaly that is palpable at <5 cm, below the
LCM, is not eligible for spleen response
Symptoms
response
A ≥50% reduction in the MPN-SAF TSS
CI: clinical improvement; LCM: left costal margin.
1. Tefferi A et al. Blood. 2013;122:1395-1398.
Revised MPN Response Criteria
• New response criteria remain clinically derived
and focus on resolution of marrow histologic
changes, blood counts, spleen size, symptom
improvement, and lack of vascular events or
progression
• All require over 12 weeks of benefit to be
counted as response
• Value and measurement of stability (clinically or
histologically) still not captured
• Validation of value of response levels needed
©2011 MFMER | 3133089-17
What should you expect of your MPN Therapy?
Individualizing Therapy
• What is the spectrum of disease burden and
risk in MPNs?
• What are expectations of therapy?
• Current and evolving treatment options for MPN
patients
©2011 MFMER | 3133089-18
Management of PV/ET
• ALL PV Patients
• Maintain HCT <45% Men, 42% Women
• Low Dose ASA
• Aggressive control of CV risk factors
• Cytoreduction
• High Risk or
• Intol to Phlebotomy, Increasing Spleen, Severe Sx
Plt >1500 x 10(9)/L, or prog WBC
• Medications
• Hydroxyurea or Interferon alpha as Front line (or second)
• Busulfan, pipobroman, P-32 as second line
Barbui T, et. al. LeukemiNET Consensus Guidelines. JCO 2011;29:761-770
Kiladjian JJ, et al. Blood 2008;112:3065
Morphologic change after
IFN therapy in a
patient with primary
myelofibrosis (After
Median 3 years of Rx).
Silver et. al. Blood 2011
•17 “Early” PMF (MF<Grade 3)
•IWG (11 low, 6 Int 1)
•INFa2b or PEG Infa-2a
•IWG-MRT
2 CR, 7 PR, 1 CI (59% Response)
Gowin et. al. ASH 2011
•17 “Early” PMF (MF<Grade 3)
•PEG Infa-2a
•IWG-MRT
1 CR, 2 PR, 1 CI (29% Response)
Silver R T et al. Blood 2011;117:6669-6672
2014 Therapeutic options for MF
Experimental
therapy
Observation
•
•
•
Low risk
Int-1 risk
Int-2 risk
High risk
•
•
•
Constitutional
Symptoms
•
Ruxolitinib
•
•
•
•
•
•
•
Myeloproliferation
And Splenomegaly
Ruxolitinib
Hydroxyurea
Busulfan
Cladribine
Splenectomy
Radiation
JAK2 inhibitor
JAK1 inhibitor
Telomerase
Inhibitor
Histone Deacetylase
inhibitors
IFN-α
Combination
therapy
ASCT
Anemia
•
•
•
Cure
Androgens
rEPO
IMiDs
•
Allogeneic Stem cell
Transplantation (ASCT)
JAK Inhibitors and Status of Development
Myelofibrosis as lead indications
Ruxolitinib (FDA Approved)
*
Pacritinib (SB1518)
Momelotinib (CYT387)
*
LY2784544
*
BMS-911543
NS-018
INCB039110 (JAK1)
Fedratininb (SAR302503)
*
No Longer in Development
For MPNs
CEP 701
XL019
* Now Testing
in PV
AZD1280
0
1
2
3
4
©2011 MFMER | 3133089-23
ASH 2013
Mean Daily Dose (mg, BID) ± SEM
Mean Daily Dose of Ruxolitinib Over Time
25
20 mg BID starting dose
15 mg BID starting dose
20
15
10
5
0
0
8
16
24
32
40
48
56
64
72
80
88
96 104 112 120 128 136 144
Weeks
Number of patients
20 mg BID
100
15 mg BID
55
98
49
93
35
77
33
73
30
69
26
62
20
• Approximately 70% of patients had dose adjustments during the first 12 weeks
of therapy
• By week 24, patients originally randomized to RUX 15 mg BID and 20 mg BID were
titrated to a mean dose of ~10 mg BID and 15-20 mg BID, respectively
24
ASH 2013
Percentage Change in Spleen Size
• Mean reductions in spleen volume and palpable spleen length with
ruxolitinib were stable over time
Spleen Volume
Ruxolitinib
Spleen Length
Placebo
Ruxolitinib
10
0
n = 148 139 120 107 100 84
73
132 107 35
-10
-20
-30
-40
-50
-60
Mean Percentage Change from Baseline
Mean Percentage Change from Baseline
10
Placebo
0
n = 153 152 150 141 130 110 102 90 79
147 141 136 109 47
-10
-20
-30
-40
-50
-60
12 24 48 72
96 120 144
Weeks
12
24
48
4
8
12 24 48 72 96 120 144
4
8
12 24
48
Weeks
25
Durability of Spleen Volume Reduction
• In patients originally randomized to ruxolitinib, 59% achieved a ≥35% reduction in
spleen volume
1.0
≥10% reduction (n=91)
Probability
0.8
≥35% reduction (n=91)
0.6
0.4
0.2
0
0
8
16
Number of patients at risk
≥35% reduction 91 86 77
24
32
40
48
56
64
72
80
88
96 104 112 120 128 136 144
Weeks from initial ≥ 35% spleen volume reduction
75
68
62
59
54
51
49
42
40
38
37
27
25
23
≥35% reduction: Time from first 35% reduction to <35% reduction and 25% increase from nadir.
≥10% reduction: Time from first 35% reduction to <10% reduction from baseline.
1
1
26
Improvements in EORTC QLQ-C30 Over Time
20
15
10
5
0
-5
-10
-15
0
12
24
36
48
60
72
84
0
-5
-10
-15
-20
-25
24
36
48
60
72
84
Weeks
0
-5
-10
-15
-20
-25
-30
-35
0
Mean Change From Baseline
25
20
15
10
5
12
5
12
24
96
108 120 132 144
36
48
60
72
84
96 108 120 132 144
Weeks
RUX
PBO
Arrows indicate improvement
Role Functioning
0
10
96 108 120 132 144
Weeks
Mean Change From Baseline
Fatigue
Mean Change From Baseline
Mean Change From Baseline
Global Health Status/QoL
Physical Functioning
15
10
5
0
-5
-10
0
12
24
36
48
60
72
84
Weeks
96
108 120 132 144
27
JAK1 & 2 Inhibitors in MPNs –
Efficacy Summary – As of ASH 2013
Myelofibrosis
Yes
No
Occasional
Not
Reported
Yet
Polycythemia
Vera
Ongoing
Trials
Essential
Thrombocythemia
Spleen
Const.
Sympt.
Anemia
Survival

Counts
Const.
Sympt.
Vasc
Events

Counts
Const.
Sympt.
Vasc
Events
Ruxolitinib - Approved
P III
P III
P III
P III
P II
P II
P II
P II
P II
P II
SAR302503 –
PH III JAKARTA (HOLD)
P III
P III
P II
P III
PacritinibPIII Ongoing (Persist MF)
P II
P II
P II
CYT387
P II
P II
P II
LY2784544
PI
PI
BMS-911543
PH II
PH II
INCB039110
PI
PI
CEP701
P II
P II
P II
P II
NS-018
PI
P II
P II
©2011 MFMER | 3133089-28
JAK1 & 2 Inhibitors in MPN – Toxicity ASH 2013
Hematological
Toxicities
Anemia

ANC
Gastrointestinal/ Renal
Toxicities

PLT
Nausea
Diarrhea

LFTs
Or CR
Ruxolitinib Approved
23%
7%
11%
SAR302503 –
PIII Ongoing (MF)
41%
6%
11%
0%
5%
1%
PacritinibPIII Ongoing (MF)
6%
0%
18%
6%
CYT387
PII Ongoing (MF)
10%
INCB039110
(JAK1) – PI/II MF
28%
BMS 911543
3%
LY2784544
3%
10%

Lipase
Neurological
Toxicities
Headache
2%
Dizzy
NeuroP/
Parathia
0.6%
W. E.
%?
2%
20%
0%
27%
10%
10%
0%
0%
0%
0%
3%
8%
Renal
1%
Toxicity Color – Represents All Grades ( Grade ¾ Toxicity - Percentage in Table Above)
<10%
1120%
2130%
3140%
4150%
5160%
6170%
7180%
8190%
91100%
©2011 MFMER | 3133089-29
Clinical Status
MPNs – Plateau vs. Decline
ET – Possible Plateau
Asymptomatic Thrombocytosis
No Vascular Events
PV – Possible Plateau 2
Symptomatic Erythrocytosis
MF
on Successful
JAK2
– Possible
Plateau
2 Rx
No VascularET
Events
Improving Weight
Symptomatic
Thrombocytosis
Decreased
Sinus VenousSpleen
Thrombosis
Improved Survival
Post PV MF
6 Months worsening Fatigue
10 kg weight loss
Massive spleen
Time
©2011 MFMER | 3133089-30
Clinical Status
MPNs – Cumulative Benefits
Ruxolitinib
Improved Survival
Improved Spleen
Burden
Improved Symptom
Burden
Time
©2011 MFMER | 3133089-31
Clinical Status
MPNs – Cumulative Benefits
Single Agent Trials JAK2 Inhibitors
Compared to Ruxo
? Other Benefit
-Less cytopenias
-Improved activity
STUDY (JAK2/FLT3 Inhibitor)
Pacritinib (SB1518) (PH III vs. BAT)
NCT01773187
Improved Survival
STUDY (JAK2/JAK1 Inhibitor)
Momelotinib (CYT387) (PH III vs. Ruxo)
NCT001969838
Improved Spleen
Burden
STUDY (JAK2/FLT3 Inhibitor)
NS-018 (PH I/II)
NCT01423851
Improved Symptom
Burden
STUDY (JAK2 Inhibitor – Also ET and PV)
LY2784544 (PH I/II)
NCT01520220
Time
©2011 MFMER | 3133089-32
IMiDs in MF: Summary of Clinical Data
HB
PLT
SPLN
REF
THAL
29%
38%
41%
Barosi 2002
THAL-PRED
62%
75%
19%
Mesa 2002
LEN
22%
50%
33%
Tefferi 2006
LEN-PRED
19%
?
9%
Mesa 2010
LEN-PRED
30%
?
42%
Quintas-Cardama
2009
POM
(0.5mg/day)
>50%
?
<25%
Mesa 2010
30-40%
40%
<10%
Tefferi 2008
POM+/-PRED
Clinical Status
MPNs – Cumulative Benefits
Ruxolitinib + drug X for Anemia
STUDY COMBINATION (JAK2 PLUS Androgen)
Ruxolitinib Plus Danazol
Mayo Clinic (AZ) and Mt. Sinai Trial: NCT01732445
Improved Anemia Burden
Improved Survival
Improved Spleen
Burden
Improved Symptom
Burden
STUDY COMBINATION(JAK2 PLUS
Hypomethylation)
Ruxolitinib Plus Azacitidine
MDACC Trial: NCT01787487
STUDY COMBINATION (JAK2 PLUS IMID)
Ruxolitinib Plus Lenalidomide
NCT01375140
STUDY COMBINATION (JAK2 PLUS IMID)
Ruxolitinib Plus Pomalidomide
Germany (ULM): NCT01644110
Time
©2011 MFMER | 3133089-34
Clinical Status
MPNs – Cumulative Benefits
Ruxolitinib + drug X for Deeper
Marrow Changes Impact
STUDY COMBINATION
(JAK2 PLUS HDAC Inhibitors)
Ruxolitinib Plus Panobinostat
Mt. Sinai Trial: NCT01693601
UK Trial: NCT01433445
Improved Marrow Dysfunction
Improved Survival
Improved Spleen
Burden
Improved Symptom
Burden
STUDY COMBINATION (JAK2 PLUS LOXL2
Inhibitors)
Ruxolitinib Plus GS-6624
NCT01369498
STUDY COMBINATION (JAK2 PLUS rhPTX-2
(Anti-fibrosing))
Ruxolitinib Plus PRM -151
Opening Soon
STUDY COMBINATION (JAK2 PLUS PI3 Kinase
Inhibitor)
Ruxolitinib Plus BKM120
NCT01730248
STUDY COMBINATION
(JAK2 PLUS Hedgehog Inhibitor)
Ruxolitinib Plus LDE225
NCT01787552
Clinical Status
MPNs – Cumulative Benefits
Single Agent Trials
Alternate Targets
STUDY (Interferons)
Peg Interferon α2b in “Early” MF
Cornell Lead: NCT01758588
? Other Benefit
-Less cytopenias
-Improved activity
Improved Survival
Improved Spleen
Burden
STUDY (Activin - ActRIIA-IgG1Fc)
Sotatercept (ACE 011)
MDACC: NCT01712308
STUDY (Telomerase Inhibitor)
Imetelstat (GRN163L)
Mayo Clinic (Rochester): NCT01731951
Improved Symptom
Burden
STUDY (JAK1 Inhibitor)
INCB039110 (PH II)
NCT01633372
Time
Clinical Status
MPNs – Cumulative Benefits
Difficult PV-ET
STUDY (ET and PV)
MPD-RC 112 Peg Inf a2a vs. Hydroxyurea (PH III)
NCT01259856
Improved Marrow Dysfunction
Improved Survival
STUDY (ET and PV)
MPD-RC 111 Peg Inf a2a AFTER Hydroxyurea
(PH III)
NCT01259856
STUDY (PV)
AOP Peg Inf a2a vs Hydroxyurea (PH III)
NCT01230775
Improved Spleen Burden
Improved Symptom Burden
Improved Vascular Event Risk
(?PV)
STUDY COMBINATION (PV)
Ruxolitinib Vs. Hydroxyurea (RELIEF)
NCT01632904
FUTURE STUDY COMBINATION
JAK2 Inhibitor Plus PEG INFa 2a/b
Myeloproliferative Disorders Research Consortium Trial
Polycythemia Vera and Essential Thrombocythemia
MPD-RC 112 (NCT01259856 – clinicaltrials.gov)
Randomized Trial of Pegylated Interferon Alfa-2a versus
Hydroxyurea Therapy in the Treatment of High Risk
Polycythemia Vera (PV) and High Risk Essential
Thrombocythemia (ET)
Registered & Randomized
High Risk ET and PV
(< 3 Months Prior Hydroxyurea)
ENDPOINTS
Primary: Complete response by ELN
Criteria
Secondary: Partial response rate by
ELN criteria, JAK2-V617F Allele Burden,
Vascular Events, MPN Symptoms,
Tolerability, Progression
Key Eligibility Criteria
PEG INF Alfa-2a
• Target dose 90
mcg/week
• Weekly Dosing
• ≥2 years of therapy in
responders
HYDROXYUREA
• Titrated Dosing to
Response
• Daily Dosing
• MPD-RC 111 in
HYDROXYUREA
Failures
• High risk PV or ET within 3 years from
diagnosis
• No prior cytoreductive treatment
(interferon or pegasys) other than
hydroxyurea for up to 3 months (prior
phlebotomy, aspirin, and/or
anagrelide allowed)
• Age of 18 or older with relatively
normal kidney and liver function
• No other serious medical problems
Questions contact MPD-RC (www.mpd-rc.org)
John Mascarenhas, MD john.mascarenhas@mssm.edu Phone: 1 (212) 241-6756
Verstovsek S, et. al. Blood (ASH) 2010;116: Abstract 313
Time to First Phlebotomy (n=1) or
Discontinuation (n=8)
• 74% (25/34) remained on study and phlebotomy-free for at least
144 weeks
Verstovsek S et. al. Blood (ASH) 2012;120:abstr 804
NOTE: Analysis does not include phlebotomies that occurred in the first 4 weeks of treatment.
40
Reduction in PV-Associated Symptoms
Verstovsek S et. al. Blood (ASH) 2012;120:abstr 804
• Clinically meaningful improvements in pruritus, night
sweats, and bone pain observed within 4 weeks of
initiating therapy and sustained through Week 144
ITT analysis: Patients who discontinued are counted as not having response for all study visits that they would have completed up to the date of analysis.
41
Medicine Wheel of Health
“Integrative Medicine”
MPN-QOL International Study Group
www.mpn-qol.org
• MEASURE Trial
• Serial assessment of MPN symptoms and QOL in
all currently available therapies
• SYMPTOM Trial
• Serial assessment of the BMT experience in MPN
symptoms (and BMT/GVHD symptoms) and QOL
• Current Landmark Survey
• mpnsurvey.com
Supported by a grant from the MPN Foundation
©2011 MFMER | 3133089-43
Individualizing MPN Pharmacotherapy
Patient Goals & Input
Improving Symptom Burden
/HR QOL
CURE
“Balancing” Spleen/
Cytoses/ Cytopenias
Extending Life
©2011 MFMER | 3133089-44
Acknowledgements
Argentina
Ana Clara Kneese, MD
Federico Sackmann, MD
Australia
David M Ross MBBS, PhD
Cecily Forsyth
John Seymour, MBBS, PhD
Karen Hall, MD
Kate Burbury MD
Tam Constantine, MD
Canada
Lynda Foltz, MD
Vikas Gupta, MD
China
Hsin-An Hou, MD
Huan-Chau Lin,
MD Hung Chang, MD
Ming-Shen Dai, MD
Yuan-Bin Yu, MD
Yung-Chen Su, MD
Zhijian Xiao, MD
Denmark
Christen Lykkegaard Andersen, MD
Hans Hasselbalch, MD
France
Brigitte Dupriez, MD
Jean-Jacques Kiladjian, MD
Jean-Loup Demory MD
Magali Demilly, PhD
Germany
Heike L. Pahl, PhD
Ireland
Mary Francis McMullen, MD
Israel
Martin Ellis, MD
Italy
Alessandro M. Vannucchi, MD
Francesco Passamonti, MD
Giovanni Barosi, MD
Tiziano Barbui, MD
Netherlands
Harry Schouten, MD, PhD
Jan Jacques Michiels, MD
Karin Klauke, MD
Peter te Boekhorst, MD
Sonja Zweegman, MD PhD
Stephanie Slot, MD
Suzan Commandeur, MD
New Zealand
Hilary Blacklock, MD
Panama
Francis Guerra, MD
Singapore
Wee Joo Chng, MB ChB
Spain
Ana Kerguelen Fuentes, MD
Carlos Besses, MD
Francisco Cervantes, MD
Dolores Fernandez-Casados
Sweden
Andreasson Bjorn, MD
Elisabeth Ejerblad, MD
Gunnar Birgegard, MD
Jan Samuelsson, MD
Johanna Ablesson, MD
Peter Johansson, MD
UK
Anthony Green, MD
Claire N. Harrison, MD
Deepti Radia, MD
Uruguay
Pablo Muxi, MD
USA
Alison Moliterno, MD
Brady Stein, MD MHS
Casey O'Connell
Catriona Jamieson
Daniel Rubin, ND
Elizabth Hexner
Hala Simm
Jason Gotlib, MD
Jeff Sloan, PhD
Jessica Altman, MD
Joseph Prchal, MD
Kimberly Hickman
Martin Tallman, MD
Mike Boxer, MD
Olatoyosi Odenike, MD
Robert Silver, MD
Ross Levine, MD
Soo Jin Kim
Srdan Verstovsek, MD
©2011 MFMER |

similar documents