OKT3 for the Treatment of Steroid-Resistant Acute Renal Allograft Rejection

Abstract

OKT3 (Orthoclone) was first used in this unit on February 25, 1987. Up until March 31, 1996, 153 patients had a total of 163 transplants. Fifty of these patients who received 53 transplants (28 male, mean age 37.5 years, 48 cadaveric donors), were treated with OKT3 for steroid-resistant acute rejection. Forty-nine graft biopsies were undertaken and 47 showed acute rejection. In the other 4 episodes a clear-cut clinical and laboratory diagnosis of severe rejection was made. OKT3 (5 mg i.v.) was started at a median of 19 days following transplantation and was successful in reversing 43 of 51 (84%) episodes of steroid-resistant acute rejection. Of those treated, the patient and graft survival at 1 year was 86 and 69%, at 3 years 82 and 64% and at 5 years 79 and 61 %, respectively. Adverse effects were common. Four patients died from sepsis within the first 3 months after transplantation. OKT3 was effective in reversing 84% of steroid-resistant acute rejection episodes.

Sequential cytomegalovirus antigenemia monitoring in kidney transplant patients treated with antilymphocyte antibodies

“…T lymphocyte activation and lysis, with release of cytokines, are responsible for CMV activation from latency (9, 20, 21). As a result, ALA therapy is responsible for a threefold increase in the rate of CMV infection, including asymptomatic infection, CMV‐related graft dysfunction, severe invasive disease, and CMV‐related death (6–9). Based on these reports, general agreement exists that antiviral prophylaxis is mandatory for patients treated with ALA.…”

“…The major risk factors for CMV disease are the pre‐transplant serologic status, with donor IgG positive and receptor IgG negative being the group at the highest risk, and the previous use of highly immunosuppressive mono‐ or polyclonal antilymphocyte antibodies, responsible for viral activation from latency and subsequent viral replication in conjunction with other immunosuppressive drugs (6–9).…”

Delayed Recovery of Accelerated Acute Rejection

“…Treatment of AAR has not been very successful, although improvements in tissue matching and the introduction of new immunosuppressive agents have improved the outcome of renal transplantation. OKT3 has been shown to be very effective in steroid‐resistant acute rejection in renal allografts 18. The Guangzhou group also reported that AAR was reversible in 6 of the 7 patients treated with OKT3 19.…”

The fate of renal allografts treated with OKT3 for steroid-resistant rejection

“…No transplante renal, a terapia antilinfocitária usada para o tratamento de rejeição aguda severa resitente aos corticosteróides, tem sido empregada em 20% a 40% dos pacientes tratados com ciclosporina (9,(11)(12)(13). Neste estudo, 19,6% dos pacientes que tiveram rejeição aguda necessitaram OKT3 como terapia de resgate.…”

“…Monaco et al (16), avaliando transplantes renais de doadores vivos e cadavéricos, também observaram uma sobrevida pobre do enxerto em 12 meses, 61%. Em outros estudos a sobrevida do enxerto em 1 ano nos pacientes com RA córtico-resistente tratados com OKT3 variou de 42% (5) a 69% (11), em acordo com os resultados descritos. Entretanto, outras séries mostraram sobrevidas melhores quando o OKT3 resgatou mais de 80% das rejeições, como 77% em 1 ano (9), 66% em 4 anos (17), 61% em 5 anos (11) e 60% em 7 anos (7).…”