Disassociation between risk of graft loss and risk of non-Hodgkin lymphoma with induction agents in renal transplant recipients.
BACKGROUND
It is widely assumed that the graft-enhancing properties of antilymphocyte induction agents and their lymphoma-inducing potential are intimately related.


METHODS
The Collaborative Transplant Study (CTS) database was used to evaluate graft survival and non-Hodgkin lymphoma at 3 years according to type of induction in 112,122 patients receiving a deceased-donor renal transplant during 1985 to 2004.


RESULTS
The relative risk of 3-year graft loss versus no induction was 1.07 (95% confidence interval [CI], 1.01-1.13; P=0.016) with murine anti-CD3 monoclonal antibody (OKT3), 1.03 (95% CI, 0.95-1.11; NS) with antithymocyte globulin (ATG)-Fresenius, 1.18 (95% CI, 1.02-1.35; P=0.021) with ATGAM, 0.74 (95% CI, 0.68-0.81; P<0.001) with Thymoglobulin, and 0.78 (95% CI, 0.72-0.84; P<0.001) with interleukin (IL)-2RA induction. The standardized incidence ratio of lymphoma compared with a similar nontransplant population was 21.5 (95% CI, 15.7-28.8; P<0.001) with OKT3, 4.9 (95% CI, 1.6-11.5; P=0.008) with ATG-Fresenius, 29.0 (95% CI, 12.5-57.1; P<0.001) with ATGAM, 21.6 (95% CI, 14.3-31.2; P<0.001) with Thymoglobulin, 7.8 (95% CI, 4.4-12.9; P<0.001) with IL-2RAs, and 9.4 (95% CI, 8.3-10.6 P<0.001) with no induction.


CONCLUSIONS
Those agents that offered the highest rates of graft survival were not necessarily associated with the highest risk of lymphoma. Graft survival was significantly improved with Thymoglobulin and IL-2RA induction, whereas lymphoma rates were highest with ATGAM, OKT3, and Thymoglobulin. IL-2RA agents seem to offer the best risk-to-benefit ratio for this patient population overall in terms of graft survival and lymphoma.
Opelz
Gerhard
G
Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. gerhard.opelz@med.uni-heidelberg.de
Naujokat
Cord
C
Daniel
Volker
V
Terness
Peter
P
Döhler
Bernd
B
D000961:Antilymphocyte Serum / Q000009:adverse effects; D016208:Databases, Factual; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced / Q000453:epidemiology*; D016853:Muromonab-CD3 / Q000009:adverse effects; D018570:Risk Assessment; D016019:Survival Analysis; D017741:Survivors; D017211:Treatment Failure
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3