Correspondence
HLA Compatibility and Graft Survival after Heart Transplantation
N Engl J Med 1994; 331:404-405August 11, 1994
- Article
To the Editor:
Opelz and Wujciak and their colleagues are to be congratulated for maintaining a multicenter registry in the Collaborative Transplant Study (March 24 issue)1. However, before their recommendations for realigning the organ-delivery system are implemented, they must first prove that the degree of HLA mismatching has an effect on the incidence and severity of the serious complication graft arteriosclerosis, which currently limits long-term survival of heart-transplant recipients2.
Furthermore, it is unrealistic to propose that 20 percent of organs can be safely set aside for emergency transplantations. As has been shown, the overall trend is for transplantation to be performed in hospitalized patients, especially those in intensive care units3. In the recent experience of the New England Organ Bank (O'Connor K: personal communication), the percentage of patients receiving transplants who came from intensive care units increased from 22.4 percent in 1990 to 62.1 percent in 1992. Hence, as the degree of illness increases among potential recipients (an effect of increased demand, broader criteria for acceptance, and effective pretransplantation care of patients with end-stage congestive heart failure), any new system of allocation must account for the risk of death while patients wait. Otherwise, the small benefit of HLA matching will be difficult to attain.
3 ReferencesPaul J. Hauptman, M.D.
Brigham and Women's Hospital, Boston, MA 021151
Opelz G ,Wujciak T . The influence of HLA compatibility on graft survival after heart transplantation. N Engl J Med 1994;330:816-819
Full Text | Web of Science | Medline2
Dec GW ,Semigran MJ ,Vlahakes GJ . Cardiac transplantation: current indications and limitations. Transplant Proc 1991;23:2095-2106
Web of Science | Medline3
Stevenson LW ,Warner SL ,Steimle AE , et al. The impending crisis awaiting cardiac transplantation: modeling a solution based on selection. Circulation 1994;89:450-457
Web of Science | Medline
To the Editor:
Given the current need for optimal allocation of organs for transplantation, we were much interested in the article by Opelz and Wujciak showing a prominent influence of HLA compatibility on the outcome of cardiac transplantation. In this respect, several groups have reported that in renal transplantation, the influence of HLA-DR mismatches on graft survival was dependent on the particular HLA-DR incompatibility between donor and recipient.
Some HLA-DR mismatches appeared to be detrimental -- that is, they resulted in worse graft survival than was expected, when they were compared with other HLA-DR mismatches. This was most consistently found among recipients with the HLA-DR6 allele1,2. On the other hand, some HLA-DR incompatibilities appeared to have no detrimental effect, leading to graft-survival rates as good as those for grafts fully matched for HLA-DR3,4. This was observed most clearly when either the donor or the recipient possessed the HLA-DR5 allele4.
It would thus be of practical interest to know whether detrimental or nondetrimental HLA-DR incompatibilities have also been identified in cardiac transplantation. Indeed, accepting the harmless mismatches would increase the likelihood of finding a suitable recipient for a cardiac transplant in a given population, and the avoidance of detrimental mismatches could help to improve graft survival in selected groups of patients.
4 ReferencesPierre Vereerstraeten, M.D.
Daniel Abramowicz, M.D.
Marc Andrien, M.D.
Hopital Erasme, 1070 Brussels, Belgium1
Hendricks GFJ ,Claas FHJ ,Persijn GG ,Witvliet MD ,Baldwin W ,Van Rood JJ . HLA-DRw6-positive recipients are high responders in renal transplantation. Transplant Proc 1983;15:1136-1138
Web of Science2
Soulillou J-P ,Bignon J-D . Poor kidney-graft survival in recipients with HLA-DRw6. N Engl J Med 1983;308:969-970
Web of Science | Medline3
Cicciarelli JC ,Perdue S ,Terasaki PI . HLA-DR3 associated with improved kidney transplant survival. Transplant Proc 1982;14:308-310
Web of Science | Medline4
Vereerstraeten P ,Andrien M ,De Pauw L , et al. Beneficial effects of some donor-recipient HLA-DR mismatches on cadaveric graft survival: proposal for a new selection policy of recipients. Transplant Proc 1991;23:385-386
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Hauptman asks for evidence that HLA mismatching affects the incidence of graft arteriosclerosis. This issue will have to be assessed in future studies since data on graft arteriosclerosis were not yet available for analysis in our study. However, it would appear to us that the significant association of post-transplantation survival with the degree of HLA matching should be sufficient reason for implementing prospective matching strategies.
The increasing frequency with which transplantation is carried out on an urgent basis raises the difficult issue of the equitable allocation of donated organs. The number of available organs is insufficient to meet the current demand. Waiting lists of potential recipients are growing, and an increasing number of patients die while waiting because suitable organs cannot be obtained in time. This situation is complicated by the fact that, although patients undergoing urgent transplantation are in desperate need, the outcome of transplantation is predictably worse than in patients not treated on an urgent basis. Among patients undergoing primary heart transplantations that were reported to the Collaborative Transplant Study from 1991 to 1993, those in the “urgent” category had a mean (±SE) survival rate of 67 ±2 percent at two years, as compared with 77 ±1 percent among patients not in this category (P<0.001 by log-rank test).
Of course, the likelihood of success cannot be the sole factor determining organ allocation Nevertheless, considering the prevailing shortage of organs, this issue requires careful evaluation. We thought that allocating 20 percent of all organs to candidates for emergency procedures was reasonable; however, this proportion could easily be adjusted.
Vereerstraeten et al. address the interesting possibility that mismatches of certain HLA antigens or certain recipient-donor antigen profiles might be more favorable than others. Such effects have been suggested on the basis of analyses of kidney transplants. We were disappointed that in a recent study, in which molecular typing techniques were used for an exact determination of the HLA-DR6 specificity,1 we were unable to confirm reports that HLA-DR6 mismatches were particularly deleterious. Nevertheless, we agree that means of predicting the effect of HLA mismatches against the background of the recipients' immunologic responsiveness should be sought. If “deleterious” HLA mismatches could be distinguished from “permissible” mismatches, efforts to provide well-matched grafts could be focused on patients who would benefit the most.
1 ReferencesGerhard Opelz, M.D.
Thomas Wujciak, M.S.
University of Heidelberg, 69120 Heidelberg, Germany1
Mytilineos J ,Scherer S ,Dunckley H , et al. DNA typing of 3500 cadaver kidney transplants does not confirm the “DR6 effect.” Transplant Proc 1993;25:207-209
Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Hauptman, Paul J., O'Connor, Kevin J., . (1997) Procurement and Allocation of Solid Organs for Transplantation. New England Journal of Medicine 336:6, 422-431
Full Text
