RELATIONSHIP BETWEEN REJECTION AND INFECTION AFTER T-CELL DEPLETING INDUCTION THERAPY

INDUCTION IMMUNOSUPPRESSION

A.C. Farney¹, J. Rogers¹, S. Al-geizawi¹, A. Reeves-daniel², E.L. Hartmann², P.L. Adams², S. Kaczmorski³, W. Doares³, M. Gautreaux⁴, S. Winfrey¹, S. Iskandar¹, R. Stratta^5
1General Surgery, Wake Forest University School of Medicine, Winston-Salem/UNITED STATES OF AMERICA, ²Internal Medicine, Wake Forest University School of Medicine, Winston-Salem/NC/UNITED STATES OF AMERICA, ³Pharmacy, Wake Forest University School of Medicine, Winston-Salem/NC/UNITED STATES OF AMERICA, ⁴General Surgery, Wake Forest University School of Medicine, Winston-Salem/NC/UNITED STATES OF AMERICA, ⁵, Wake Forest University School of Medicine, Winston-Salem/UNITED STATES OF AMERICA

Body: Introduction: The risk of allograft rejection must be balanced against the risk of infection due to over-immunosuppression (IS). Methods: We studied the relationship between biopsy proven acute rejection (BPAR) and infection events (IEs) within a randomized controlled clinical trial that compared depleting antibody induction with alemtuzumab (alem) vs rabbit anti-thymocyte globulin (rATG) in kidney (KTx) and pancreas (PTx) transplantation. Maintenance IS included FK, MPA, and steroid taper or withdrawal. Infection prophylaxes were given for fungal (1 month KTx; 2 month PTx), pneumocystis (12 month), and CMV infections (3 months; 6 months for primary CMV exposure). If IEs occurred, MPA dose was reduced by half during the acute illness. Results: Between 2/1/05 and 8/1/07 (median follow-up 24 months), 225 patients (pts) were enrolled and 222 pts (180 KTx, 38 KPTx, and 4 PTx after KTx) were treated (113 randomized to Alem and 109 to rATG induction). BPAR occurred in 44 (20%) pts, but was lower in the Alem (16, 14%) vs the rATG group (28, 26%, p = 0.02). Of 113 alem pts, 56 (50%) had at least one IE, compared to 75 (69%) of those in the rATG group (p=0.02). Overall, 131 (56%) had at least one IE, but 32 (73%) pts with BPAR had IEs.Relationship Between 1st IE Type and BPAR

IE Type	Bacterial	Fungal	Viral	Total
BPAR (n=44)	24 (55%)	2 (5%)	6 (14%)	32 (73%)
no BPAR (n=178)	75 (42%)	5 (3%)	19 (11%)	99 (56%)*

*vs BPAR, p=0.04 Of 44 pts with BPAR, 17 (39%) had 2nd IEs, compared to 44 (25%) patients who had 2nd IEs but no BPAR (p=NS). On average, 1st IEs and 2nd IEs occurred at 3.4 and 6.7 months, whereas BPAR occurred at 5.3 months. FK levels, steroid use, total rATG induction dose, and absolute neutrophil and lymphocyte counts had no impact on incidence of IEs. However, MPA daily doses were lower at most time points in the first year in pts who had IEs. Conclusions: Both BPAR and IEs were less common in the alem induction group. IEs were common even in pts without BPAR, but those with BPAR had the highest incidence of IEs. IEs, particularly bacterial IEs, commonly preceded BPAR, but a trend in more IEs was also seen after BPAR. A lower daily dose of MPA, reduced in the setting of IEs, may partially explain a higher incidence of BPAR associated with rATG as compared to alem induction. The relationship between infection and BPAR is complicated, as IEs may increase risk for subsequent BPAR, but BPAR may also predispose to infection.

Disclosure: All authors have declared no conflicts of interest.