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

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150 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 (US)
Pages (from-to)2619-2625
Number of pages7
JournalAmerican Journal of Transplantation
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2007

Keywords

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

ASJC Scopus subject areas

  • Immunology

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    Kirk, A. D., Cherikh, W. S., Ring, M., Burke, G., Kaufman, D., Knechtle, S. J., Potdar, S., Shapiro, R., Dharnidharka, V. R., & Kauffman, H. M. (2007). Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. American Journal of Transplantation, 7(11), 2619-2625. https://doi.org/10.1111/j.1600-6143.2007.01972.x