Induction Immunosuppression Effect on Pancreas Transplant Outcome

Induction therapy immunosuppression agents can be divided into two main groups: 1) T-cell depleting polyclonal antibodies (e.g. Thymoglobulin (TMG), ATGAM) or monoclonal antibodies (E.G. OKT3, Campath); and 20 non-depleting monoclonal anti-CD-25 directed antibodies (e.g. Zenapax, Simulect).  In each pancreas transplant category, the recipients treated with one or more induction antibodies was >75%. For SPK, depleting and non-depleting antibodies are nearly equal in their use, while for PAK or PTA the depleting antibodies have been used more frequently (Figure 22).

Figure 22

By univariate model, primary DD SPK GSR outcomes at 1 year for maintenance immunosuppression TAC+MMF differed significantly (p=<0.03) by induction therapy subgroups: 91% for non-depleting antibody; 85% for depleting antibody; 86% for no antibody (Figure 23a).  This relative difference was similar in the ED SPK cases, but no clear advantage was found for BD SPK cases. By univariate model for primary DD PAK cases, GSR outcomes at 1 year for maintenance immunosuppression TAC+MMF were highest for those given depleting antibodies either alone or in combination (p=0.02), 85% independently of the duct management technique, and lowest for recipients not given any induction antibody therapy (Figure 23b). By univariate model for primary DD PTA cases, GSR outcomes at 1 year for maintenance immunosuppression TAC+MMF did not differ significantly (p=>0.50) between the non-depleting and depleting antibody induction therapy groups.  The majority received depleting antibodies alone (38%) or a combination of depleting and non-depleting antibody therapy (36%); only 16% received no antibody induction therapy (Figure 23c).  By duct management technique, again there were no differences in GSRs by antibody induction therapy.

Figure 23a

Figure 23b

Figure 23c

By multivariate model (Table 8), neither non-depleting nor depleting antibody antibody therapy had statistically significant impact on primary DD SPK pancreas graft failure rates (GFRs) (p=>0.16). However, for the technically successful (TS) SPK cases, immunological HR graft loss of 0.63 for non-depleting antibody therapy showed some advantage (p=0.09).  The multivariate model for primary DD PAK cases confirmed the univariate outcomes by showing a reduction in overall GFR with a HR of 0.74 (p=0.08) and no significant impact (p=0.55) for non-depleting antibody therapy.  For TS PAK cases, no significant risk was found for the non-depleting antibody therapy subgroup, while depleting antibody therapy was associated with a slight reduction in immunological graft loss risk.  In the multivariate model for primary DD PTA cases, there was no clear difference in outcomes according to whether depleting or non-depleting antibody therapy was used (p=>0.17).

Table 8.    Cox – regression for immunological pancreas graft failure (technically successful US DD primary pancreas transplants 1/1/2000 – 6/2004)

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