Chest
Volume 109, Issue 5, May 1996, Pages 1184-1189
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Total Lymphoid Irradiation for Refractory Acute Rejection in Heart-Lung and Lung Allografts

https://doi.org/10.1378/chest.109.5.1184Get rights and content

Persistent or recurrent acute allograft rejection (AR) refractory to high-dose steroid therapy can adversely affect long-term outcomes of heart-lung (HLT), bilateral-lung (BLT), and single-lung (SLT) transplantations. The use of total lymphoid irradiation (TLI) for the management of refractory acute AR in six transplant recipients (two men, four women; mean age, 29.8±3.8 years) is detailed. There are two HLT (primary pulmonary hypertension [PPH], cystic fibrosis [CF]), 1 BLT (pulmonary hypertension postventricular septal defect repair), and 3 SLT (sarcoid, PPH, congenital heart disease with atrial septal defect) recipients. Refractory AR is defined as persistent rejection unresponsive to high-dose steroid therapy in all cases. The BLT and SLT recipients had at least two moderate and one mild AR events per patient. The HLT recipients had at least two moderate acute heart and one severe and one mild asynchronous acute lung rejection events per patient. A total of 800 cGy of total lymphoid irradiation (TLI) was administered over a 5-week period. Mild and transient leukopenia was the only observed side effect. The patient with PPH received TLI 313 days after HLT for recurrent AR at another institution and died of ARDS 4 weeks after completing TLI. The patient with CF received TLI 707 days after HLT and died 457 days after TLI of severe obliterative bronchiolitis (OB) with multiorgan failure. The patient with BLT received TLI 176 days after transplant and died 372 days after TLI of respiratory failure related to severe rejection. One patient with SLT received TLI 78 days after transplant and died 679 days after TLI of severe acute AR. The two remaining patients with SLTs have been free from acute AR for more than 4 years. The patient with sarcoidosis received TLI 37 days after SLT following a clinical rejection event and two severe acute AR events. He is alive with normal lung function 5 years later. The patient with PPH received TLI 108 days after SLT following three moderate acute AR events and is alive with stable OB 4 years later. These limited preliminary results suggest that TLI has merit for the treatment of intractable acute AR following HLT and lung transplantation.

Section snippets

Patients

Twenty-seven HLTs, 11 single-lung transplants (SLTs), and 6 bilateral-lung transplants (BLTs) in adults (age >18 years) were performed between August 1989 and January 1992. Six of these patients (TLI group) received TLI after repeated IV boluses of MP and optimization of cyclosporine and azathioprine therapy failed to reverse repetitive or intractable acute cellular rejection. Twenty-three of the 38 patients (rejector group) had at least one AR that required MP bolus therapy. The remaining 15

RESULTS

The clinical data of the patients who received TLI for refractory rejection are summarized in Table 1. Briefly, there were four women and two men ranging in age from 26 to 34 years with a mean and SD of 29.8±3.8. Table 2 summarizes the TLI specifications. The median pre-TLI period was 142 days (range, 37 to 707 days). The mean duration and SD of TLI was 34±4 days. The median post-TLI period to February 1,1995 was 568 days (range, 51 to 1,937 days). The overall median survival time in this

DISCUSSION

Radiotherapy for clinical transplantation was originally administered in the form of total body irradiation more than 3 decades ago to induce prolonged renal allograft acceptance.13 However, it was limited by unacceptable severe bone marrow and GI toxic reactions.

The subsequent refinements in the fractionation, dose per fraction, total radiation dose, and mode of delivery minimized the total radiation exposure and targeted the therapy to the lymphatic system. These modifications in combination

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