title: Successful reversal of acute cardiac allograft rejection with OKT*3 monoclonal antibody.
abstract: The efficacy of OKT*3 monoclonal antibody in reversing acute cardiac allograft rejection was investigated in 10 cardiac transplant recipients aged 5 to 57 years (mean 34 +/- 18) and treated with the same induction and maintenance immunosuppression. Serial endomyocardial biopsies, right heart catheterization, and echocardiograms were performed for rejection surveillance. After intensified immunosuppression with equine antithymocyte globulins and steroids, nine patients showed persistent rejection (lymphocytic infiltration and myocyte necrosis). Conventional immunosuppression was contraindicated in one patient. OKT*3 (5 mg by intravenous push daily for 14 days) resulted in complete resolution of rejection in nine of 10 patients (90%). After therapy with OKT*3 mean right atrial and pulmonary arterial wedge pressure were significantly lower (9.1 +/- 4.0 vs 4.8 +/- 2.0 mm Hg and 13.4 +/- 4.3 vs 8.0 +/- 3.3 mm Hg, respectively; p less than .05). Cardiac index was doubled in two patients with rejection-induced cardiac dysfunction (1.5 vs 3.2 and 1.6 vs 2.7 liters/min/m2). Only two patients developed antibodies to OKT*3. Fever, nausea and headache occurred with the first three doses of OKT*3 and did not recur. One patient developed aseptic meningitis. OKT*3 effectively reverses refractory cardiac allograft rejection before the development of irreversible graft dysfunction. Patients who do not develop antibodies to OKT*3 can be retreated with this drug. Adverse reactions to OKT*3 are self-limited.
authors.affiliation: Department of Medicine, Loyola University Medical Center, Maywood, IL 60153.
authors.forename: M R
authors.initials: MR
authors.lastname: Costanzo-Nordin
authors.forename: M A
authors.initials: MA
authors.lastname: Silver
authors.forename: J B
authors.initials: JB
authors.lastname: O'Connell
authors.forename: R
authors.initials: R
authors.lastname: Pifarre
authors.forename: K L
authors.initials: KL
authors.lastname: Grady
authors.forename: G L
authors.initials: GL
authors.lastname: Winters
authors.forename: D K
authors.initials: DK
authors.lastname: Murdock
authors.forename: H J
authors.initials: HJ
authors.lastname: Sullivan
authors.forename: J G
authors.initials: JG
authors.lastname: Grieco
authors.forename: P J
authors.initials: PJ
authors.lastname: Scanlon
mesh_terms: D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000032:analysis; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D012008:Recurrence; D013601:T-Lymphocytes; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents