Ea. Hammond et al., PREVENTION OF ADVERSE CLINICAL OUTCOME BY MONITORING OF CARDIAC TRANSPLANT PATIENTS FOR MURINE MONOCLONAL CD3 ANTIBODY (OKT3) SENSITIZATION, Transplantation, 55(5), 1993, pp. 1061-1063
We have previously reported that patients sensitized to murine monoclo
nal CD3 antibody (OKT3) and maintained on such therapy for induction o
f immunosuppression have a high mortality and/or allograft loss. In th
is follow-up study, we retrospectively reviewed all patients routinely
and serially monitored by flow cytometry for plasma levels of OKT3 du
ring a 21-month period beginning 1/90. A total of 112 patients were mo
nitored during this period. We retrospectively tabulated the incidence
of OKT3 sensitization, rejection pattern and impact on survival of wi
thdrawal of OKT3 at the time of sensitization as compared with the pre
vious study in which withdrawal was not done. Nine patients were exclu
ded from analysis because of withdrawal for reasons other than sensiti
zation: cytokine encephalopathy, infection, postoperative complication
s, or severe rejection. Twelve patients had OKT3 therapy aborted becau
se of failure to achieve steady-state OKT3 levels or because of declin
e in levels while on therapy. These patients were thus defined as bein
g sensitized to OKT3. No patient was aborted because of return of CD3
cells in the blood. Only one of the 12 patients sensitized to OKT3 die
d. Of 91 patients with steady-state OKT3 levels, 6 had high plasma lev
els (>1000 ng/ml) and 6 had low plasma levels (<500 ng/ml). None of th
ese patients had OKT3 therapy aborted and all are alive. Twelve of the
se 91 patients had successful retreatment with OKT3 for refractory rej
ection, indicating that absence of sensitization on induction predicts
safety of retreatment with OKT3. We also examined the frequency of as
sociated human antimouse antibody (HAMA) production using the blocking
assay modified from Jaffers and Mayes. Only the sensitized patients e
xhibited a significant association with HAMA production (6/7 tested, P
=0.05) Classification of the rejection pattern of the sensitized patie
nts confirmed our previous results: eight of 12 had vascular rejection
and 4/12 had mixed rejection. These patterns were prospectively deter
mined. We conclude that serial monitoring of patients for plasma level
s of OKT3 is an effective strategy to prevent adverse outcomes of indu
ction with this agent.