Treatment of steroid-resistant and recurrent acute cardiac transplant rejection with a short course of antibody therapy.
The purpose of this study was to assess the efficacy of short courses of OKT3 and ATG, respectively, for steroid resistant or recurrent acute allograft cardiac rejection (AR). Between June 1988 and March 1994, 101 heart transplant patients were treated with a quadruple sequential immunosuppression protocol (ATG, azathioprine, CsA, and prednisone). AR was diagnosed by endomyocardial biopsy (EMB), and patients with scores > 2 (ISHLT) received pulse methylprednisolone, 500 mg i.v. on 3 consecutive days. In cases of steroid-resistant or recurrent AR, OKT3 (5 mg/d) or ATG (1.5-2.5 mg/kg/d), was administered for 5-7 d instead of the usual 10-14 d course. OKT3 (17 courses; 10 steroid resistant, 7 recurrent AR; 5.3 +/- 0.7 doses) was given to 16 patients (4F/12M, 45 +/- 11 yr), 29-269 d after transplantation. ATG (8 courses; 5 steroid resistant, 3 recurrent AR; 4.9 +/- 0.6 doses) was given to 8 patients (1F/7M, 53 +/- 7 yr), 23-503 d after transplantation. Successful treatment of AR with a score < 2 at the first and second EMB after treatment was 88% and 88% with OKT3, and 87.5% and 100% with ATG, respectively. Throughout follow-up (50 +/- 22 months after OKT3; 49 +/- 28 months after ATG), there was a trend towards lower incidence of subsequent AR after ATG (25% vs. 69%, P = 0.09), and similar incidence of infections, graft atherosclerosis and mortality. No cases of lymphoproliferative disorder were observed. We conclude that short courses of OKT3 or ATG are safe and effective for the treatment of steroid resistant or recurrent AR, with a similar incidence of complications. These results may have cost-effectiveness implications and need to be confirmed in a randomized study.
Cantarovich
M
M
Department of Medicine, Victoria Hospital, McGill University, Montreal, Canada.
Latter
D A
DA
Loertscher
R
R
D000208:Acute Disease; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000209:etiology; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use; D001424:Bacterial Infections; D001706:Biopsy; D003362:Cost-Benefit Analysis; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D015996:Survival Rate; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone; D008775:Methylprednisolone