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A combined DST-sequential CyA therapy protocol has been described that results in optimum graft survival for 1- and 2-haplotype mismatched living related donor-recipient combinations. In addition to the excellent graft survival obtained through 4 years, lower prednisone and CyA dosage levels are achieved with significantly decreased infection rates during the posttransplant period.

Pre-BTs significantly improve the survival rate for first cadaver transplants, by a mechanism that remains obscure. The maximal influence is seen with smaller numbers of pre-BTs (1-5 units), but is also observed with larger numbers of pre-BTs. The possible beneficial influence of Tx-BTs on graft survival is not proven, and if it exists at all is not nearly as striking as the effect seen with pre-BTs. Tx-BTs neither potentiate nor nullify the benefit of pre-BTs on graft survival. It is therefore recommended that pre-BTs in smaller numbers, such as 1-5 units, be administered to candidates for first cadaver transplants to increase the probability of a successful outcome. Tx-BTs should be utilized when clinically indicated but not with the expectation that they will necessarily improve graft survival.

Prospective pretreatment with deliberate DST has afforded MLC reactive related donor-recipient pairs enhanced opportunity for successful transplantation. The sensitization rate in patients receiving DST prior to primary transplantation was 30%, but this sensitization has been generally specific and narrow-those patients developing a positive DSXM do not appear to be jeopardized regarding later cadaver transplantation. Graft survival rates in 86 recipients of kidneys from their blood donors are 95% (1-year) and 93% (2-year). This graft survival rate appears to outweigh the minimal risk of possible unfavorable sensitization. Potentially unsuccessful transplants in immunologically disparate related donor-recipient pairs can be avoided, and the transplants actually performed have enhanced prospects of success.

In this study, pretransplant transfusions significantly improved the survival of first cadaver kidney transplants. Large numbers of transfusions had the same influence on graft survival as small number of transfusions. Graft survival was not influenced by pretransplant antibody levels, and the beneficial effect of transfusions was also independent of highest pretransplant antibody levels. The positive relationship between transfusions and cytotoxic antibodies was shown to be highly significant. B-warm and T-warm antibodies were both increased by transfusions and tended to occur together. B-cold antibodies occurred independent of transfusions, B-warm and T-warm antibodies. The results of this study suggest, but do not confirm, that B-cold antibodies benefit graft survival, while T-warm antibodies adversely influence graft survival. Transfusions and B-cold antibodies appear to influence graft survival by different mechanisms.

DST provides excellent graft survival in one- and zero-haplotype-matched donor-recipient pairs as well as a trend towards improving graft survival in HLA-identical matches; serum creatinine levels are good in functioning grafts; Imuran coverage does appear to decrease DST sensitization to the blood donor in nonsensitized patients undergoing a first transplant, which encourages early DST and transplantation in this group; flow cytometry has been extremely helpful in excluding subliminal anti-class 1 antigen activity in patients with positive B warm crossmatches alone; DST, in itself, does not appear to preclude subsequent cadaveric transplantation in patients sensitized to their blood donor; and the family history of the blood donor is known, with essentially no risk to the recipients of hepatitis, AIDS, etc. In regards to the issue of whether DST or Cs is better, both have merits, and one must be aware of the circumstances that relate to the optimum application of each therapy. Only a prospective study of DST- and Cs-treated patients with a long-term follow-up will probably resolve the issue of the optimum regimen for one-haplotype-matched living related donor-recipient pairs. The ultimate strategy may involve the selective use of each regimen for the most appropriate circumstances.

Analysis of 463 consecutive primary cadaver renal transplants showed no influence of HLA match grade on renal allograft survival. Additional categorization according to HLA match grade and degree of presensitization again showed no correlation between match grade and graft survival. Mismatches and matches of specific antigens, cross-reacting groups of antigens, and effect of matching at both locus A and B were also evaluated. There was no significant effect on graft survival except when mismatches against donor A2 and cross-reacting group A2, A28 occurred. A trend toward better graft survival was suggested in recipients matched for A9 and cross-reacting group A9, Aw 23, Aw 24. Although HLA match grade did not influence ultimate graft survival, HLA typing remains important, especially to avoid mismatch against donor A2 antigen. In addition, subsequent detection of new specificities, particularly in other than the A and B loci, may provide significance in the future.

Pretreatment with deliberate DST has not resulted in hyperacute or irreversible rejection in patients receiving kidneys after negative donor-specific crossmatches, but has afforded immunologically disparate related recipients enhanced opportunity at successful transplantation. Additionally, with a post-transplant course paralleling that of HLA-identical siblings, high-dose immunosuppressive therapy for rejection has been spared in many recipients. Transplantation, however, proved unsuccessful in a patient receiving a kidney from his positive B-warm crossmatch blood donor in a protocol departure. This case experience and subsequent antibody studies have reconfirmed our initially established criterion of not proceeding with transplantation against a persistently positive B-warm donor-specific crossmatch. By pursuing the initially established DST protocol, it appears that a potentially unsuccessful living related transplant can be avoided, while the transplants actually performed have enhanced prospects of success. The nature of the various immunologic responses in this patient population remain to be more clearly defined.