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

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

Research output: Contribution to journalArticle

145 Citations (Scopus)

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 1 2007

Fingerprint

Kidney Diseases
T-Lymphocytes
alemtuzumab
Muromonab-CD3
Tissue and Organ Procurement
Organ Transplantation
B-Lymphocytes
Maintenance
thymoglobulin
Databases
Transplants
Kidney
Antibodies
Incidence

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. / Kirk, A. D.; Cherikh, W. S.; Ring, M.; Burke, George W; Kaufman, D.; Knechtle, S. J.; Potdar, S.; Shapiro, R.; Dharnidharka, V. R.; Kauffman, H. M.

In: American Journal of Transplantation, Vol. 7, No. 11, 01.11.2007, p. 2619-2625.

Research output: Contribution to journalArticle

Kirk, AD, Cherikh, WS, Ring, M, Burke, GW, Kaufman, D, Knechtle, SJ, Potdar, S, Shapiro, R, Dharnidharka, VR & Kauffman, HM 2007, 'Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab', American Journal of Transplantation, vol. 7, no. 11, pp. 2619-2625. https://doi.org/10.1111/j.1600-6143.2007.01972.x
Kirk, A. D. ; Cherikh, W. S. ; Ring, M. ; Burke, George W ; Kaufman, D. ; Knechtle, S. J. ; Potdar, S. ; Shapiro, R. ; Dharnidharka, V. R. ; Kauffman, H. M. / Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. In: American Journal of Transplantation. 2007 ; Vol. 7, No. 11. pp. 2619-2625.
@article{3b29a797ae944d2c8f42386c2f53a049,
title = "Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab",
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.",
keywords = "Depletion, Induction therapy, Kidney transplantation, Posttransplant lymphoproliferative disease",
author = "Kirk, {A. D.} and Cherikh, {W. S.} and M. Ring and Burke, {George W} and D. Kaufman and Knechtle, {S. J.} and S. Potdar and R. Shapiro and Dharnidharka, {V. R.} and Kauffman, {H. M.}",
year = "2007",
month = "11",
day = "1",
doi = "10.1111/j.1600-6143.2007.01972.x",
language = "English",
volume = "7",
pages = "2619--2625",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab

AU - Kirk, A. D.

AU - Cherikh, W. S.

AU - Ring, M.

AU - Burke, George W

AU - Kaufman, D.

AU - Knechtle, S. J.

AU - Potdar, S.

AU - Shapiro, R.

AU - Dharnidharka, V. R.

AU - Kauffman, H. M.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - 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.

AB - 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.

KW - Depletion

KW - Induction therapy

KW - Kidney transplantation

KW - Posttransplant lymphoproliferative disease

UR - http://www.scopus.com/inward/record.url?scp=35248887465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35248887465&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2007.01972.x

DO - 10.1111/j.1600-6143.2007.01972.x

M3 - Article

C2 - 17868060

AN - SCOPUS:35248887465

VL - 7

SP - 2619

EP - 2625

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 11

ER -