Figure 1
May 1, 2007
The recent article in Lancet Oncology (8:212-18, 2007) demonstrates the value of results that can be derived from the CTS with respect to posttransplant malignancies. We were surprised to find that prophylaxis with antivirals did not have the expected preventive effect on non-Hodgkin lymphomas. Instead, we made the interesting observation that prophylaxis with anti-CMV immunoglobulin (which contains antibodies against CMV and EBV) appears to prevent the occurrence of early posttransplant lymphomas. Naturally, a retrospective registry analysis cannot provide definitive proof. Prospective studies will be necessary to ascertain the validity of our findings. Nevertheless, it is important to consider that these observations would not have been possible without the tireless efforts of the CTS participants who provided information on posttransplant malignancies for many years.
In the context of the previously mentioned success of this initiative, I would like to, again, appeal to CTS participants who have not yet returned the "Cancer Confirmation Questionnaire" to please do so in the near future. We expect to obtain more clinically relevant findings in this particular research area. The involvement of a large number of patients is an essential prerequisite for valid studies on the incidence of posttransplant tumors and factors that may affect their occurrence. The CTS database is probably the largest and best documented reservoir of data on posttransplant malignancies. Please support our efforts to conduct meaningful epidemiological research on posttransplant tumors. Because of the well-known potential problem of underreporting, we must insist on the return of the green "Cancer Confirmation Questionnaire" in order to include your center in the cancer study. Your support of this important initiative is highly appreciated!
The question as to which crossmatch technique is best has been discussed for many years. Detailed single-center laboratory studies have been very informative in this respect. In the CTS registry, it is not possible to document individual crossmatch results in great detail. This must be considered a drawback; nevertheless, one can obtain an overall impression with respect to clinical efficacy based on everyday procedures. We are therefore presenting to you an analysis of crossmatch results reported to the CTS.
Figure 1
As shown in Figure 1, positive crossmatch results obtained with T-cell or B-cell targets were associated with a statistically significant reduction of the graft survival rate. The lower graft survival rate associated with positive flow crossmatches did not reach statistical significance. Unfortunately, we do not have information on the associated circumstance of the 351 transplants that were performed despite a positive T-cell crossmatch. Presumably, these were weakly positive results or the transplants were done deliberately or mistakenly in spite of a strongly positive crossmatch. Positive B-cell crossmatches, on the other hand, are commonly ignored and transplants are routinely done when the B-cell crossmatch is positive, provided the T-cell crossmatch is negative.
Figure 2 shows the same analysis for retransplants. The results roughly parallel those of first grafts, with the exception that positive T-cell crossmatches were clearly associated with the lowest graft success rate.
Figure 2
Of interest in this context is whether B-cell reactivity in the documented absence of T-cell reactivity was associated with impaired graft outcome. The results are shown in Figures 3 and 4. Both in the analysis of first and retransplants, positive B-cell crossmatches in the absence of T-cell reactivity were associated with a significant reduction of graft survival. The B-cell crossmatches analyzed for this newsletter were performed at a 37º C incubation temperature.
Figure 3
Figure 4
Altogether, these results confirm previous reports supporting the clinical relevance of positive B-cell crossmatches. While one can speculate that the lower success rate associated with a positive B-cell crossmatch was due to a higher sensitivity of B-cell targets for detecting weak HLA antibodies, it appears conceivable that clinically relevant non-HLA antibodies may also be detected in the B-cell crossmatch assay. The results shown in Figures 1 and 2 raise some doubt about the superiority of the flow crossmatch technology as compared to conventional serology.
Transplant centers located in countries belonging to the Eurotransplant area will be pleased to learn that the collaborative ties between Eurotransplant and CTS have been strengthened further. Due to a recent data exchange agreement, duplicate reporting will be entirely eliminated. This should further improve the quality of reporting to the two registries. We at the CTS are very pleased with the excellent cooperation that has been established with Eurotransplant as well as the Italian, Catalan, United Kingdom, and Australia-New Zealand transplant registries.
We would like to remind you that the next shipping date for the serum and DNA studies is
May 21/22, 2007
We very much depend on your active support of these important laboratory projects. The serum study is of special interest and represents our research focus at this time. Please participate actively. For details, consult the CTS website: www.ctstransplant.org (Special Studies) or contact us per e-mail.
Thank you for your continued support.
Sincerely yours,