Efficacy of OKT3 therapy for acute rejection in isolated lung transplantation.
The purpose of this study was to evaluate the efficacy of muromonal-CD3 (Orthoclone OKT3) in the treatment of acute lung rejection. Criteria for its administration were (1) steroid-resistant acute rejection, (2) first-line therapy for grade III or higher acute rejection, and (3) second relapse after tapering off steroid treatment of acute rejection. During the period between May 1990 and May 1992, 41 patients had a total of 101 episodes of acute rejection. OKT3 (5 mg/kg for 7 to 10 days) was administered to 28 patients, of whom 19 responded (68%). Nine patients had either nonresponsive episodes or relapses immediately after completion of OKT3 therapy. Age, gender, cytomegalovirus status, underlying diseases, and type of procedure did not influence the outcome. Timing of OKT3 administration, however, was important; 16 (89%) of 18 patients responded to OKT3 therapy when administered during the first 6 months after transplantation, whereas 3 (30%) of 10 patients responded only beyond 6 months (p < 0.01). Infectious complications occurred after six treatments (21%), in which high-dose steroids were used concurrently (three Aspergillus, two Pseudomonas, and one cytomegalovirus pneumonia). Two patients also taking high-dose steroids had lymphoproliferative disorders. Three allergic reactions developed: one case of edema, one case of hypotension, and one case of arthralgia-myalgia syndrome. Serum antibody titers against OKT3 were persistently negative despite repeat (up to four times) therapy. We conclude that OKT3 is an effective and relatively safe therapy for steroid-resistant, high-grade, or relapsing acute lung rejection during the first 6 months. Antimicrobial prophylaxis must be considered when OKT3 is administered.
Shennib
H
H
Joint Marseille-Montreal Lung Transplant Program, Quebec, Canada.
Massard
G
G
Reynaud
M
M
Noirclerc
M
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001228:Aspergillosis; D002648:Child; D003550:Cystic Fibrosis / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000209:etiology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use*; D011014:Pneumonia / Q000382:microbiology; D011552:Pseudomonas Infections; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome
D016853:Muromonab-CD3; D008775:Methylprednisolone