TOTAL LYMPHOID IRRADIATION IN THE TREATMENT OF EARLY OR RECURRENT HEART-TRANSPLANT REJECTION

Purpose: Recurrent acute cardiac allograft rejection is an important c ause of repeat hospitalization and a major mode of mortality, particul arly during the 6 months immediately following transplant. Total lymph oid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecd otal reports of clinical experience have also suggested efficacy of TL I in treatment of recurrent cardiac rejection. The purpose of this stu dy is to evaluate the safety and efficacy of TLI for treatment of earl y or recurrent heart transplant rejection. Materials and Methods: Betw een January 1990 and June 1992, 49 patients postallograft cardiac tran splant were given courses of TLI for treatment of early or recurrent r ejection after conventional therapy with Methylprednisolone, antithymo cyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a s econd TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), an d recurrent rejection with vasculitis (n = 6). The dose goal of the TL I protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of tre atment was 8 to 106 days. These variations were secondary to leukopeni a or thrombocytopenia. Results: The mean posttransplant follow-up is 1 5 +/- 1.2 months (maximum 27 months). Among patients initiating TLI wi thin 1 month posttransplant (n = 15), the rejection frequency decrease d from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/mo nth post-TLI (p < 0.0001). For those who began TLI 1-3 months after tr ansplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/pati ent/month (p < 0.0001). When TLI was started more than 3 months posttr ansplant (n = 11), the pre-TLI and post-TLI rejection frequencies were 0.67 and 0.07/patient/month (p < 0.0001), respectively. The reduced p ost-TLI rejection frequencies were maintained to 24 months. There was no increase in the frequency of infection after TLI, nor were there an y deaths during or immediately following TLI. Conclusion: Total lympho id irradiation is a safe and effective adjuuct for prolonged control o f early or recurrent cardiac rejection. Bone marrow suppression is tra nsient in nearly all patients and is not associated with an increased incidence of infection. The long-term benefits, possible late deleteri ous effects, and the potential role of TLI as induction therapy remain to be elucidated.