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Efficacy of OKT3 retreatment for refractory cardiac allograft rejection
J B O'Connell1, D G Renlund, W A Gay
1Utah Transplantation Affiliated Hospitals (UTAH), Cardiac Transplant Program, Salt Lake City 84132.
Abstract:
Although OKT3 monoclonal antibody is a useful therapy for refractory cardiac allograft rejection, the use of OKT3 for prophylaxis may be limited by the potential of sensitization and subsequent loss of efficacy on retreatment. OKT3 was required for refractory rejection in 21 of 165 recipients transplanted between March 1985 and August 1988. Twelve of these patients had previously been exposed to OKT3, and the retreatment efficacy was evaluated. The study population averaged 42.1 +/- 15.3 years of age (mean +/- SEM) and had experienced 2 +/- 1 previous episodes of rejection. The prior episodes of rejection had been treated with pulse methylprednisolone and antithymocyte globulin, and in addition 3 patients (25%) also required a course of antilymphoblast globulin. Retreatment OKT3 for refractory rejection was required 120 +/- 94 days following transplantation. CD3+ lymphocytes were eliminated from the circulation within 24-48 hr in 11 of 12 patients, all of whom showed histologic improvement within the first week. Total resolution on the initial follow-up biopsy was noted in 9 (75%) during the course of therapy. Subsequent rejection episodes occurred in 9 (82%) of the survivors at 71 +/- 64 days. One-year survival was 83% in this vigorously rejecting patient population. Serious infections occurred within 3 months of therapy in 4 (36%). The side effects of OKT3 retreatment were similar to those seen with first exposure and did not require OKT3 discontinuation. Thus OKT3 may be administered with success in most patients who have previously been exposed to it.
Insights
Retreatment with OKT3 monoclonal antibody is effective for refractory cardiac allograft rejection, even after prior exposure. Most patients showed improvement, with similar side effects to initial treatment, suggesting OKT3 can be successfully readministered.
Area of Science:
- Immunology
- Transplantation Medicine
- Pharmacology
Background:
- OKT3 monoclonal antibody is used for refractory cardiac allograft rejection.
- Potential sensitization and loss of efficacy limit OKT3 use for prophylaxis.
- Previous exposure to OKT3 may affect retreatment efficacy.
Purpose of the Study:
- To evaluate the efficacy and safety of OKT3 retreatment in cardiac transplant recipients with refractory rejection.
- To assess the impact of prior OKT3 exposure on retreatment outcomes.
Main Methods:
- Retrospective analysis of 12 cardiac transplant recipients previously exposed to OKT3.
- Evaluation of CD3+ lymphocyte depletion, histologic improvement, and rejection recurrence.
- Monitoring of patient survival and adverse events, including infections.
Main Results:
- CD3+ lymphocytes were eliminated in 11 of 12 patients within 24-48 hours.
- 9 (75%) patients achieved total resolution of rejection on initial biopsy.
- One-year survival was 83%, with serious infections in 36% within 3 months.
Conclusions:
- OKT3 retreatment is successful in most patients previously exposed to it.
- Side effects of retreatment are similar to initial exposure and do not necessitate discontinuation.
- OKT3 remains a viable option for managing refractory cardiac allograft rejection, even upon re-exposure.