Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab

A. D. Kirk*, W. S. Cherikh, M. Ring, G. Burke, D. Kaufman, S. J. Knechtle, S. Potdar, R. Shapiro, V. R. Dharnidharka, H. M. Kauffman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.

Original languageEnglish
Pages (from-to)2619-2625
Number of pages7
JournalAmerican Journal of Transplantation
Volume7
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • Depletion
  • Induction therapy
  • Kidney transplantation
  • Posttransplant lymphoproliferative disease

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