Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids

R. A. McDonald, J. M. Smith, M. Ho, R. Lindblad, D. Ikle, P. Grimm, R. Wyatt, Mazen Y Arar, D. Liereman, N. Bridges, W. Harmon, J. Springate, B. Warshaw, S. El-Dahr, S. Bartosh, R. Hurley, Paul Grimm, M. Benfield, R. McDonald, G. LumR. Weiss, Z. Kadry, I. Davis, R. Fennel, R. Munoz, S. Mendley, C. Wong

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9%) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged ≤5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient- (D+/R-) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age ≤5 years (RH 3.2, 95% CI: 1.1-9.6, p = 0.034) and EBV D+/R- status (RH 7.7, 95% CI: 1.6-35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.

Original languageEnglish (US)
Pages (from-to)984-989
Number of pages6
JournalAmerican Journal of Transplantation
Volume8
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Lymphoproliferative Disorders
Sirolimus
Human Herpesvirus 4
Steroids
Pediatrics
Kidney
Immunosuppression
Incidence
Tissue Donors
Transplants
basiliximab
Transplant Recipients
Calcineurin Inhibitors
Population

Keywords

  • EBV
  • Pediatric
  • PTLD
  • Renal transplant

ASJC Scopus subject areas

  • Immunology

Cite this

Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. / McDonald, R. A.; Smith, J. M.; Ho, M.; Lindblad, R.; Ikle, D.; Grimm, P.; Wyatt, R.; Arar, Mazen Y; Liereman, D.; Bridges, N.; Harmon, W.; Springate, J.; Warshaw, B.; El-Dahr, S.; Bartosh, S.; Hurley, R.; Grimm, Paul; Benfield, M.; McDonald, R.; Lum, G.; Weiss, R.; Kadry, Z.; Davis, I.; Fennel, R.; Munoz, R.; Mendley, S.; Wong, C.

In: American Journal of Transplantation, Vol. 8, No. 5, 05.2008, p. 984-989.

Research output: Contribution to journalArticle

McDonald, RA, Smith, JM, Ho, M, Lindblad, R, Ikle, D, Grimm, P, Wyatt, R, Arar, MY, Liereman, D, Bridges, N, Harmon, W, Springate, J, Warshaw, B, El-Dahr, S, Bartosh, S, Hurley, R, Grimm, P, Benfield, M, McDonald, R, Lum, G, Weiss, R, Kadry, Z, Davis, I, Fennel, R, Munoz, R, Mendley, S & Wong, C 2008, 'Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids', American Journal of Transplantation, vol. 8, no. 5, pp. 984-989. https://doi.org/10.1111/j.1600-6143.2008.02167.x
McDonald, R. A. ; Smith, J. M. ; Ho, M. ; Lindblad, R. ; Ikle, D. ; Grimm, P. ; Wyatt, R. ; Arar, Mazen Y ; Liereman, D. ; Bridges, N. ; Harmon, W. ; Springate, J. ; Warshaw, B. ; El-Dahr, S. ; Bartosh, S. ; Hurley, R. ; Grimm, Paul ; Benfield, M. ; McDonald, R. ; Lum, G. ; Weiss, R. ; Kadry, Z. ; Davis, I. ; Fennel, R. ; Munoz, R. ; Mendley, S. ; Wong, C. / Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. In: American Journal of Transplantation. 2008 ; Vol. 8, No. 5. pp. 984-989.
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abstract = "Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9{\%}) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged ≤5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient- (D+/R-) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age ≤5 years (RH 3.2, 95{\%} CI: 1.1-9.6, p = 0.034) and EBV D+/R- status (RH 7.7, 95{\%} CI: 1.6-35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.",
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AU - Grimm, P.

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AU - Lum, G.

AU - Weiss, R.

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AU - Wong, C.

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