CTS Collaborative Transplant Study

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1 CTS Collaborative Transplant Study Newsletter 3:22 October 1, 22 The CTS website has received a face lift. The new layout is modern and fresh. In addition, when analyzing your own center's results, you can now adjust the x-axis for the desired number of years. This is especially relevant when an analysis is performed for transplants done during the last few years. Because follow up is often not sufficient for meaningful statistics, the standard 5-year scale sometimes produces erratic curves. Reducing the interval scale on the x-axis will give more meaningful results. All website survival statistics have been updated. I have noticed an increase in the number of requests for center-specific password replacements. Please be sure to safeguard your password in a secure place. If it is definitely lost, you can request a new password, however, please consider that installation of the new password will take a few days. Also, for data protection reasons, we have to send centerspecific passwords by post rather than . Therefore, keeping a close eye on your center's password is important. Many centers have indicated that they are collecting sera for the scd3 and antibody project. If at all possible, we would like you to send the sera at the previously announced shipping date: November 19/2, 22. This will make things easier for us logistically. Under exceptional circumstances, we will of course accept parcels shipped on other days. Thank you for your understanding. Samples for the DNA study can be included in the same package. Please be sure to indicate clearly whether your parcel contains material for either one or both studies (DNA and serum). All tubes must be capped very tightly in order to prevent leakage. Preferably, the caps should be secured with adhesive tape. Please do not forget to attach a list showing the dates of sampling and the recipient's name or CTS key.

2 CTS Newsletter 3:22 Page 2 We would like to share with you the interesting results of a CTS analysis on simultaneous kidney + liver or kidney + heart transplants. As you may recall, a "unique graft protective role" of the liver was proposed based on the early observation that graft rejection appeared to be very rare in combined kidney + liver transplants (Margreiter et al., Transplant Proc 2:522, 1988). It was suggested that, since the liver contains large amounts of lymphatic tissue, a release of soluble HLA antigens, apoptosis of alloreactive T-cells, activation of regulatory/suppressor cells, or induction of microchimerism may take place and prevent graft rejection. However, Katznelson and Cecka, in an analysis of UNOS data, were unable to confirm the proposed protective effect of the liver on a simultaneous kidney graft (Transplantation 61:143, 1996). In a recent analysis of CTS data, we found strong evidence for a graft-protective effect of the liver. In order to allow an appropriate comparison, 3 "kidney only" transplants were selected as controls for each combined kidney + liver transplant. The controls were matched for factors such as recipient and donor age, gender, and race, cold ischemic preservation time, year of transplantation, immunosuppressive regimen, PRA, and HLA match. As shown in Figure 1, combined kidney + liver transplants had a higher failure rate initially after transplantation, however, the attrition rate following the first few months was lower than that of "kidney only" transplants. n= 364 n= Figure 1 Examined more closely, it is evident that combined grafts have a considerably higher failure rate during the first couple of months (Figure 2) and that the 1-year outcome is significantly better in recipients of isolated kidney grafts (p<.1).

3 CTS Newsletter 3:22 Page 3 n=192 n= Months Figure 2 Considering the higher comorbidity of recipients of combined transplants, the higher initial failure rate, which was entirely due to patient death, is not surprising. Importantly, if one starts the survival analysis again at % at 1 year, subsequent kidney graft outcome is strikingly better in recipients of combined transplants (Figure 3, p=.13). n=255 n= Figure 3 The half-life computation for the period following the first posttransplant year shows a result that is clearly in favor of the combined kidney + liver procedure (Figure 4).

4 CTS Newsletter 3:22 Page 4 (log) Year Half Life Estimate () 45 % % n= 364 n=192 Figure 4 The effect was present both in patients with primary oxalosis and in patients with other underlying diseases. Having confirmed the graft-protective effect of the liver on a simultaneous kidney transplant, we performed a control analysis of kidney + heart transplants. Since the heart is not nearly as rich in lymphatic tissue as the liver, we did not expect to find a prolongation effect. To our surprise, however, kidney grafts in recipients of combined kidney + heart transplants did just as well as those in recipients of combined kidney + liver transplants (Figures 5 and 6). Kidney + Heart n=297 n= Figure 5

5 CTS Newsletter 3:22 Page 5 (log) Year Half Life Estimate () Kidney + Heart 48 % % Kidney + Heart n= 99 n=297 Figure 6 The concept of the "uniqueness" of liver-induced kidney graft protection must be reconsidered in the light of these results. Evidently, the heart is just as effective as the liver in conveying graft protection. Since the control groups in both analyses were carefully matched, it is unlikely that the better kidney survival rate in recipients of combined transplants is due to an inappropriate comparison of patient groups. If indeed immunological unresponsiveness was induced by the additional graft, richness in lymphatic tissue can hardly be the explanation. Possible alternative reasons could be the higher amounts of immunosuppressive drugs administered or a particularly good patient compliance in recipients of combined organ transplants. Whatever the reason, the finding that a simultaneous heart provides the same extent of protection as a simultaneous liver is astounding. In a couple of weeks we will send you the yearly "Cancer Confirmation Questionnaires". I should like to point out that for those who regularly check for posttransplant malignancies with all CTS follow up reports, completing the questionnaire should not require any additional effort. The purpose of the questionnaire is not to ask for the complete cancer status on your patients on one particular day. Rather, it is to ensure that all posttransplant cancers have been included with your transplant follow up reports. If all cancers were not recorded together with your clinical follow up grading, we request that the cancer status should be checked now. The CTS maintains the largest and most complete database on posttransplant malignancies. Please assist us with ensuring that the records are accurate and complete. Because underreporting is a common problem with cancer statistics, completion of the special malignancy questionnaire is a precondition for inclusion of your center in the CTS cancer analysis. Thank you very much for your cooperation.

6 CTS Newsletter 3:22 Page 6 Would you please be so kind and check whether the contact address for your center shown on the CTS website is still correct. We have been repeatedly contacted because of nonfunctional addresses. Please send corrections either directly to the CTS webmaster or to me personally. Thank you for your continued support. Sincerely yours, Gerhard Opelz Prof. G. Opelz, Transplant Immunology, University of Heidelberg Im Neuenheimer Feld 35, D Heidelberg, Germany Phone: Fax: gerhard.opelz@med.uni-heidelberg.de Website: