March 1, 2000
The last few months were exceptionally demanding on our computer staff. In addition to the Y2K change-over, we embarked on a complete overhaul of the CTS database system. This change had become necessary in order to provide the flexibility required for the planned expansion of our Internet capabilities. I am now happy to report that all critical steps in this massive computer project have been expertly dealt with and completed. The CTS study is running with a new database and new peripheral software. You will notice only minor changes on the various printouts and data request forms. The main innovation in the future will be the ability for all participating centers to analyze their own data via the net by remote access. Much work remains to be done, however, before this feat will be accomplished. We expect a first version for remote access data analysis to be available by the end of the year.
Although our computing resources were concentrated on this major change-over during this period, we have accomplished a few website improvements as well. The graphical illustration of analysis results is now subdivided into the sections "Graft Survival", "Patient Survival" and "Bar Diagram". Consequently, data retrieval from the website has become less confusing. The listing of CTS publications has also been extended to include abstracts where available and a search function allows searching of all abstracts for key words. Lastly, CTS Newsletters dating back to 1984 are now available via the net. Many interesting and otherwise unpublished details were reported in these Newsletters. For instance, the Newsletter 2/1984 contains the results of a special project in which compatibility for various red cell and complement markers was investigated. The project was abandoned because we did not find any evidence for a role of these antigens in renal transplantation.
For the next Newsletter and website release, which is scheduled for June 1, 2000, we will concentrate on the Internet graphics section. This will include an increase in the number of graphs as well as an update of all (old and new) analyses according to the most recent follow up. Therefore, in order to provide us with sufficient time for including all new information in the next website release, I would like to appeal to you to return the completed "Update Section" of your printout by May 1 at the latest.
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The majority of CTS participants have furnished us with information for the website contact address. We have learned that this feature has already been very useful. If your center's address is not yet on the website, please send us the necessary information by completing the form which is attached to this month's data printout.
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I would like to remind you to check whether all transplants performed at your center in 1999 are listed on your printout. If not, please report any missing cases as soon as possible. In order to avoid any exclusion bias, it is very important that all consecutive cases be reported, even if a graft should have failed very soon after transplantation for non-immunological reasons.
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For all new personnel who may not be familiar with the CTS ground rules, I would like to repeat my yearly appeal for honest, complete and accurate reporting. There is nothing to be gained by withholding information on failures. On the contrary, the sincere research efforts of all other CTS participants would be jeopardized by inaccurate reporting. The results of individual centers are not released. Our aims are strictly scientific and our search for facts can be successful only if each individual contributing data to the study respects the principle of honest and accurate reporting. I would also like to use this opportunity to thank all who are supporting our unique international research project. It is your individual contribution and that of many like-minded individuals around the world that makes the CTS so successful. A special word of thanks is due to those who take their time to complete the yearly colored follow up forms. While these forms are more cumbersome to complete than the "Update Section" computer printout, they have become the most informative and productive part of the entire CTS effort. Please consider completing these yearly follow up forms as a high priority.
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The next shipping date for the DNA typing project is
June 05 - 06, 2000
Be sure to send us the shipping details by fax or e-mail in order to avoid the loss of any parcels at the airport. Frozen material on donors and recipients of kidney, heart, and liver transplants is requested for this special project. We will gladly provide information to centers wishing to join.
The latest analysis shows a gratifying trend for continued improvement of the HLA typing quality at laboratories participating in the DNA project. Without any doubt, this is the result of most laboratories having converted to DNA typing for HLA-DRB. The comparison of typing results for HLA-DR reported to the CTS and retyped in Heidelberg using DNA technology shows a discrepancy rate of 14% for the period prior to 1990, 11% for the period 1990-1992, 8% for 1993-1995, and 6% for typings done since 1995. Altogether, 68,248 samples have been processed! We hope that a similar improvement can be achieved in the future with typing for the HLA-A and -B loci, where our initial analyses showed considerable error rates when serological and DNA typing results were compared (Mytilineos et al., Tissue Antigens 50:355, 1997, and Human Immunology 59:512, 1998).
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Several new primer sets have been added to the list of available CTS typing reagents. Please consult the website for detailed information.
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The four year follow up of the Steroid Withdrawal Project will be available later this year. We might be able to provide you with the results in the next Newsletter, provided all questionnaires are returned in time. This is an ongoing CTS project in which patients are continuously enrolled. The preliminary results are so encouraging that we highly recommend the enrollment of all patients who meet the inclusion criteria. Please let us know if you need detailed information.
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The analysis of pretransplant risk categories published in the last Newsletter has prompted numerous comments and requests. Many were surprised to see that a loosely defined categorization could result in such clearcut results. One should not forget, however, that the simple fact that reasons were requested for judging a patient to be at an increased risk provided some guidance. We have now analyzed the most commonly reported risk indicators. As shown in Figure 1, the observed graft survival rates were within a narrow range in kidney recipients who were considered at moderate or poor risk based on the factors immunology, age, diabetes, compliance, cardio-vascular disease, obesity, or liver disease. This result is surprising since we commented in the last Newsletter that the increased risk appeared to be attributable to co-morbidity which in turn influenced primarily patient survival and not graft survival. Why would immunological risk and anticipated compliance problems have a similar impact as factors with a systemic influence?
Figure 1
The analysis of patient survival in the same recipient groups provides an interesting answer to this question (Figure 2). Clearly, recipients considered at an increased immunological risk did not have an impaired patient survival rate. Their poor graft outcome was attributable to a high rate of immunological graft rejection. Patients in whom compliance problems were foreseen formed an intermediate group. One can assume that in this group increased rejections resulted from inadequate immunosuppression, and that the patient survival rate may have been additionally affected by poor compliance with other medications. Another interesting finding is the poor success rate in patients for whom the risk factor "obesity" was indicated.
Figure 2
Several study participants asked for a parallel analysis of pretransplant risk assessment in heart and liver recipients. The results are shown in Figures 3 and 4. Unlike in kidney transplantation, there is little difference between graft and patient survival in heart and liver transplantation. Therefore, the results shown in Figures 3 and 4, although shown for graft survival, are representative also for patient survival. One could argue that the risk categorization might simply reflect the patient's underlying disease (e.g. chronic hepatitis or malignant liver disease). However, we found in subsequent analysis steps (not shown) that even within the various groups of underlying diseases, graft outcome in the three risk categories was strikingly different. These data support our contention that assigning risk categories to patients prior to transplantation provides useful information. We believe that this factor can be integrated advantageously into multivariate graft and patient survival analysis models.
Figure 3
Figure 4
Please feel free to send me your comments on these or any other issues that you consider suitable for discussion in the CTS Newsletter.
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Thank you for your continued support of the international study.
Sincerely yours,