3/6/2017
Pre-transplant Treatment
of the Sensitized Patient
Sumeet Singh Mitter, MD, MSc
Advanced Heart Failure and Transplant Cardiology Fellow
Northwestern University, Feinberg School of Medicine
Chicago, IL, USA
Sean Pinney, MD
Director, Heart Failure and Transplantation
The Icahn School of Medicine at Mount Sinai
New York, NY, USA
Sumeet Singh Mitter, MD, MSc
Advanced Heart Failure and Transplant Cardiology Fellow
Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
Sean Pinney, MD
Director, Heart Failure and Transplantation
The Icahn School of Medicine at Mount Sinai, New York, New York, USA
No financial relationships with commercial interests to disclose.
AND
The presentation does not include discussion of off-label or
investigational use.
Learning Objectives
1. Understand when to consider IVIG and
Rituximab for desensitization in a sensitized
patient pre-heart transplant
2. Understand when to consider Bortezomib
and Plasmapheresis for desensitization in a
sensitized patient pre-heart transplant
3. Understand when to consider induction
immunosuppression post-heart
transplantation
1
3/6/2017
CASE:
January 2014
36 year old female with a Left Main coronary artery spontaneous dissection requiring
urgent PCI, however with acute heart failure requiring urgent CABG (LIMA to LAD, SVG
to Diagonal 1, SVG to Obtuse Marginal 1).
August 2014
Vitals: HR 90 bpm, BP 84/50 (61) mmHg
GDMT: Carvedilol 6.25 mg BID, Lisinopril 5mg Daily, Spironolactone 50mg Daily
Labs: Hemoglobin 12.8 mg/dl, Sodium 133 mg/dl, Creatinine 0.9 mg/dl
Hemodynamics: RA 5 mmHg, 35/15 (24) mmHg, Wedge 19 mmHg, PA Sat 59%,
Thermo CI 2.1 LPM/m2
CPET: VO2/kg Max 14.6 mL/kg/min
LVEDD 5.9 cm
LVEF 10%
Severe RV dysfunction
Severe Biatrial dilatation
Moderate MR
Moderate TR
PA SP 33 mmHg
PATIENT PRA:
HLA Class I 99%, Class II 8%
2
Antibodies
Antibodies
Antibodies
3/6/2017
A*23:01
A*24:02
A*24:03
A*25:01
A*32:01
A*34:01
B*13:01
B*13:02
B*27:05
B*35:01
B*37:01
B*38:01
B*44:02
B*44:03
B*47:01
B*49:01
B*50:01
B*51:01
B*51:02
B*52:01
B*53:01
B*56:01
B*57:01
B*57:03
B*58:01
B*59:01
B62(15:01)
B63(15:16)
B71(15:10)
B72(15:03)
B75(15:02)
B77(15:13)
8/29/2014, MFI
8531.8
8022.02
7503.69
6791.62
9882.34
4726.59
7238.53
8967.74
5915.4
7301.64
5195.36
8839.73
5471.11
7898.84
6194.53
14668.98
11431.88
7730.92
11374.73
7610.56
8624.67
7869.77
10511.28
10517.02
10644.42
7888.54
8087.71
11158.28
6806.94
7436.46
6745.92
9922.93
A*23:01
A*24:02
A*24:03
A*25:01
A*32:01
A*34:01
B*13:01
B*13:02
B*27:05
B*35:01
B*37:01
B*38:01
B*44:02
B*44:03
B*47:01
B*49:01
B*50:01
B*51:01
B*51:02
B*52:01
B*53:01
B*56:01
B*57:01
B*57:03
B*58:01
B*59:01
B62(15:01)
B63(15:16)
B71(15:10)
B72(15:03)
B75(15:02)
B77(15:13)
10/6/2014, MFI
7536.39
7125.85
6553.19
6395.88
9092.29
3175.27
4782.05
6223.95
4640.02
4944.27
3607.49
7291.52
4115.98
6440.42
4307.8
11435.21
7801.31
6368.95
8565.22
5653.46
6609.68
5549.87
8732.77
8904.45
8513.02
6026.79
5525.82
8559.94
4485.28
4801.78
4515.61
7387.4
A*23:01
A*24:02
A*24:03
A*25:01
A*32:01
A*34:01
B*13:01
B*13:02
B*27:05
B*35:01
B*37:01
B*38:01
B*44:02
B*44:03
B*47:01
B*49:01
B*50:01
B*51:01
B*51:02
B*52:01
B*53:01
B*56:01
B*57:01
B*57:03
B*58:01
B*59:01
B62(15:01)
B63(15:16)
B71(15:10)
B72(15:03)
B75(15:02)
B77(15:13)
10/27/2014, MFI
2514.36
2316.97
2000.37
2035.01
3057.97
2415.13
1358.84
1827.54
1368.71
1579.21
1186.32
2481.23
1117.38
1918.14
1252.64
4374.49
2379.82
2072.92
2932.09
1726.13
2109.14
1713.22
3336.17
3166.8
2954.68
2073.89
1701.4
3139.08
1314.74
1386.36
1314.53
2564.87
9/4-9/5/14: IVIG x 2
9/7/2014: Rituximab
9/22/2014: Rituximab
9/30-10/1/2014: IVIG x 2
10/10/14:
Plasmapharesis
Bortezomib
10/6/2014, MFI
7536.39
7125.85
6553.19
6395.88
9092.29
3175.27
4782.05
6223.95
4640.02
4944.27
3607.49
7291.52
4115.98
6440.42
4307.8
11435.21
7801.31
6368.95
8565.22
5653.46
6609.68
5549.87
8732.77
8904.45
8513.02
6026.79
5525.82
8559.94
4485.28
4801.78
4515.61
7387.4
10/27/2014, MFI
2514.36
2316.97
2000.37
2035.01
3057.97
2415.13
1358.84
1827.54
1368.71
1579.21
1186.32
2481.23
1117.38
1918.14
1252.64
4374.49
2379.82
2072.92
2932.09
1726.13
2109.14
1713.22
3336.17
3166.8
2954.68
2073.89
1701.4
3139.08
1314.74
1386.36
1314.53
2564.87
11/21/2014, MFI
2523.56
2219.27
2074.69
1889.87
3189.58
1506.04
1236.64
1839.37
1418.81
1378.34
2543.23
11/01/14
Plasmapharesis
Bortezomib
1870.84
1124.93
4294.08
2269.29
2181.78
3177.16
1897.83
2232.71
1544.98
3203.05
3231.95
3191.75
2021.03
1548.01
3088.08
1307.83
1396.62
1174.67
2424.35
3
3/6/2017
MFI RESPONSE TO PLASMAPHERSIS
AND BORTEZOMIB
GT
15000
MFI
10000
5000
2
cl
e
e
Po
st
cy
cy
cl
Pr
e
Pr
e
cy
cl
e
2
1
0
DONOR OFFER 1/31/15
1/31/2015
DONOR HLA TYPING
HLA Class I Antigens:
A2,3; B18,64; Bw6; C7,8;
HLA Class II Antigens:
DR7,16:01,51, 53(DRB4*01:01); DQ2,5, DQA1*01,02;
DPB1*04:01,04:02, DPA1*01
HISTORICAL DSA
9/18/2014 & 10/6/2014
HLA Class I Antibodies
A2 (1:1)
HLA Class II Antibodies
DR7 (1:1), DR53 (1:4)
4
3/6/2017
FLOW CROSSMATCH NEGATIVE
Channel Shift
Serum Date
Dilution
T
B
1:1
+1
+5
1:2
0
+1
1:8
0
-4
1:1
-1
+44
+5
+9
1/31/2015
11/21/2014
2SD Cutoff
DONOR ACCEPTED
ISCHEMIC TIME:
211 Minutes
INDUCTION:
ATG x 5 doses targeting CD3 < 50
MAINTENANCE:
TACROLIMUS, MMF, PREDNISONE
POST-TRANSPLANT
1st DSA 2/2/2015
HLA Class I Antibodies:
NEGATIVE
HLA Class II Antibodies:
NEGATIVE
Echo and Right Heart Cath 2/10/2015
EF 55%
RA 4, PA 20/6 (13), PW 6, CI 2.8
5
3/6/2017
POST-TRANSPLANT
RECENT DSA 1/25/2017
HLA Class I Antibodies:
NEGATIVE
HLA Class II Antibodies:
NEGATIVE
ECHO and Right and Left Heart Cath 1/25/2017
EF 55%
RA 8, PA 22/11 (16), PW 11, CI 3.1
Angiographically Normal Coronaries
THE END
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