Date: Saturday, June 11, 2016
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
Introduction: Alemtuzumab induction followed by a steroid-free, tacrolimus (Tac) and mycophenolate mofetil (MMF) based regimen effectively prevented acute rejection after simultaneous pancreas-kidney transplantation (SPKT). Acute rejection was rare in the first three months with a second peak between 3 to 6 months, despite comparable Tac and MMF exposure and similar reconstitution of immune cells in patients with and without rejection. Here, we investigated whether later acute rejections were associated with alemtuzumab plasma levels, since significant interpatient variability has been reported in non-solid organ transplant studies. Methods: This retrospective cohort study included 73 consecutive SPKT recipients, all receiving alemtuzumab induction (15 mg SC, day 0 & 1) and steroid-free maintenance with Tac and MMF. Alemtuzumab levels were measured with ELISA on 3 time points in 10 patients with acute rejection within 6 months and 10 control patients without rejection. Kaplan-Meier estimate (log rank) was used to compare time to undetectable plasma levels. Results: A total of 15 patients (20.5%) experienced acute rejection in the first year after SPKT: two patients <3 months, eight between 3 to 6 months, and five between month 6 to 12. Plasma alemtuzumab levels showed great interpatient variability, ranging from 0.04 to 0.30 [micro]g/mL at month 1 and undetectable to 0.08 [micro]g/mL at month 3. In 13 out of 20 patients (6 controls, 7 rejections) alemtuzumab levels were undetectable (<0.01[micro]gl/mL) at 3 months. Plasma alemtuzumab levels were not associated with acute rejection (log rank 0.486). Despite comparable therapeutic drug monitoring results, 10 of 15 first acute rejection episodes were preceded by standard (empiric) dose reduction at 3 months or an additional reduction due to intercurrent infections or leukopenia. Conclusion: Alemtuzumab levels in SPKT recipients showed great interpatient variability, there was however no association with therapeutic drug monitoring parameters and acute rejection episodes beyond 3 months. The observation that late acute rejections were associated with intercurrent infections and additional dose reductions, suggests that these empiric reductions in Tac or MMF, in the absence of steroids, constitute an increased risk for late acute rejection in SPKT.
CITATION INFORMATION: Bank J, Mallat M, Jol-van der Zijde C, Bredius R, van der Boog P, Braat A, Ringers J, Reinders M, de Fijter J. Plasma Alemtuzumab Levels Show Great Interpatient Variability, but Are Not Associated with Late Acute Rejection in Simultaneous Pancreas-Kidney Recipients. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Bank J, Mallat M, Zijde CJol-vander, Bredius R, Boog Pvander, Braat A, Ringers J, Reinders M, Fijter Jde. Plasma Alemtuzumab Levels Show Great Interpatient Variability, but Are Not Associated with Late Acute Rejection in Simultaneous Pancreas-Kidney Recipients. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/plasma-alemtuzumab-levels-show-great-interpatient-variability-but-are-not-associated-with-late-acute-rejection-in-simultaneous-pancreas-kidney-recipients/. Accessed April 20, 2021.
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