marc halushka md, phd johns hopkins university som 10 th banff conference on allograft pathology...
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AMR Current Practice Survey - North America
Marc Halushka MD, PhDJohns Hopkins University SOM
10th Banff Conference on Allograft PathologyAugust 12, 2009
Disclosures
No Relevant Financial Relationships with Commercial Interests & No Reference to an Unlabeled or Unapproved use of a Drug or
Product
Marc Halushka, MD, PhD
To understand the range of methods different institutions use to evaluate AMR.
To recognize the range of protocols different institutions have regarding evaluating AMR.
To realize that the time is upon us to develop a consensus guideline for AMR.
Objectives
Implementation of the ISHLT 2004 criteria
What centers doing regarding the evaluation of antibody-mediated (AMR/ humoral) rejection? (How much AMR are different groups reporting?)
Two Areas of Variability
Survey of pathologists at US and Canadian heart transplantation centers
Queried about use and comfort with the ISHLT 2004 criteria & AMR-related practices
Johns Hopkins Cardiac Transplantation Survey
Identified 113 US Centers and 9 Canadian Centers that performed heart transplantations in 2008 (UNOS and Dr. Veinot – U of Ottawa).
Identified one pathologist per institution who read cardiac transplantation biopsies (via websites, colleagues, phone calls to pathology departments/practices, etc).
Generated survey questions, placed these on SurveyMonkey and had the questions piloted by 4 cardiovascular pathology colleagues who assessed accuracy and coverage.
Survey was open from April 16, 2009 through May 20, 2009. Multiple reminder emails were sent, reminder phone calls were made and continuous updates made to reach the appropriate pathologists and maximize inclusion.
Survey Information
94 Respondents
• 78% of transplant centers
• 82% of all transplants in 2008
Represents a good cross-section of US and Canadian centers
Survey Response
90% of centers reported evaluating for AMR.
Centers that did not evaluate tended to perform fewer biopsies per year but were otherwise similar to other centers.
Centers evaluating for AMR
Never Very Rarely (≤1%)
Rarely (2-5%)
Occasionally (6-10%)
Often (11-30%)
0
5
10
15
20
25
30
35
Prevalence of AMR as a percent of all transplant biopsies
Cou
nt o
f C
ente
rs
1% 40% 40% 18% 2%
~20%~80%
Regional Variation in AMR
% of Centers >5% AMR levels
0%
8%
19%30-35%
60%
No data from AK, DL, HI, ID, ME, MS, MT, ND, NH, NM, NV, RI, SD, UT, VT, WV, WY
All biopsies Limited biopsies0
10
20
30
40
50
60
Standard Protocols for Investigating AMR
25%
Cou
nt o
f C
ente
rs
75%
Clinica
l Sus
picion
Sugge
stive
H&E
1st 3
mon
ths
1st y
ear
Cellula
r Reje
ction
PRAs
ABO Inco
mpa
tible
0
10
20
30
40
50
Limited Protocols for Investigating AMR
62% 13% 4% 4%39% 3% 1%
Cou
nt o
f C
ente
rs
Staining Protocols for AMR
C4d IHC
C4d IF
CD68
C3d IF IgG
IgM C3
IgA
C1q
CD31
Fibrin
Fibrin
ogen
C3d IHC C4
HLA-DR
Kappa
Lambda
Album
in05
101520253035404550
C3d IF4%
C4d Both IF & IHC21%
C4d IF36%
C4d IHC39%
Cou
nt o
f C
ente
rs
Association between staining protocol and AMR
C4d IHC C4d IF Both0%
5%
10%
15%
20%
25%
30%
35%
40%
Ce
nte
rs r
epo
rtin
g >
5%
AM
R
*
*OR = 3.15 p=0.05
“It would be good to know what the standard is for screening for AMR. It seems that by the time we are seeing positive IF (done only by request based on clinical suspicion), the clinical picture is so dire that the patients do not do well.”
“Criteria on when to automatically test for humoral rejection would be useful. We occasionally see staining of only a few capillaries or blood vessels with C4d. We comment on it, but it would be nice to have a standardized way of grading / handling C4d staining.”
“I have tried to assess humoral rejection and have found it impossible to interpret.”
Survey Comments
“The aspect of biopsy grading that needs further standardization is AMR. When you talk to colleagues at other institutions, everyone is doing something different - different indications, different techniques, different interpretation. The clinical side needs to be addressed as well. If we have positive C4d staining and the patient is fine, no one knows what to do.”
Survey Comments
Conclusions Prevalence of AMR: ~20% of centers report >5% of all biopsies have AMR. This varies regionally. Evaluation of AMR: 90% of transplant centers do evaluate – nearing consensus Protocol for AMR: 25% of centers evaluate every biopsy for AMR. Numerous other limited protocols exist. – need for consensus Staining for AMR: Wide variability in C4d staining protocols (IF, IHC, both). 60% of centers also stain for other proteins (immunoglobulins, etc) – need for consensus