Incidence of De-Novo Donor Specific Anti-Human Leucocyte Antigen (HLA) Antibodies (DSA) in Simultaneous Pancreas Kidney (SPK) Transplant Patients: A comparison between alemtuzumab and basiliximab based immunosuppression regimes

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Abstract

Introduction

De-novo Donor Specific Human Leucocyte Antigen (HLA) Antibodies (DSA) are detrimental to organ transplants. Few studies have explored the incidence of DSA’s and subsequent outcomes after SPK transplant, and none have compared different immunosuppression regimes. The aim of this study was to compare two different immunosuppression regimes (Alemtuzumab versus Basiliximab) with regard to the development of DSA and their long-term outcomes.

Materials and Methods

We introduced Alemtuzumab for all our SPK recipients from March 2008 onwards along with a Tacrolimus and MMF (from day 7) for maintenance. Prior to this, we used Basiliximab along with our standard immunosuppression regime of a CNI, MMF and steroids. We performed a retrospective analysis of all our SPK transplant patients between 2003 – June 2016. DSA were measured as early (within 2 years) and late (>2 years post-transplantation). HLA antibody testing was performed as per clinical need using a Luminex 200 flow cytometer (Luminex, Inc., Austin, TX). Samples were initially screened for the presence or absence of HLA antibodies using Labscreen mixed HLA antibody screening kits (One Lambda Inc., Canoga Park, CA, USA). For all positive and reactive results, HLA antibody specificities were determined using a combination of Lifecodes ID (Immucor USA) and Labscreen single antigen kits (One Lambda Inc.). Data was analysed using Microsoft Excel 2011 and SPSS 23. Chi-square test was used to compare the groups.

Results and Discussion

A total of 83 SPK transplants were performed Alemtuzumab (n=53) and Basiliximab (n=30). For early DSA, 20 patients were tested in the Basiliximab group; none developed DSA. In contrast, 34% patients (14 out of 41 tested) in the Alemtuzumab group developed early DSA (p=0.009). Of those 14 patients, 3 (21%) lost their kidney grafts, 6 (43%) lost their pancreas and 3 (21%) eventually died. For late DSA, 18 patients were tested in the Basiliximab group and 3 (17%) were found to be positive. 2/3 patients suffered pancreas graft loss, 1 lost the kidney graft and 1 died as a complication of post-transplant lymphoproliferative disorder. In the Alemtuzumab group, 12 (41%) out of 29 tested developed DSA (p=0.077). Out of those 12 patients, 4 (33%) kidneys and 5 (42%) pancreas were lost and 3 (25%) deaths were recorded. 11 patients (92%) out of the 12 who were positive for late DSA, had early DSA as well.

Conclusion

Patients on an Alemtuzumab based regime had a significantly higher incidence of early DSA in comparison to a Basiliximab based regime in those patients that were tested. A higher proportion continued to develop late DSA in the Alemtuzumab group. The presence of DSA was associated with very high rates of both pancreas and kidney graft loss.

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