Transplant immunology · 2025
Novel, short-course, low-dose total lymphoid irradiation (TLI) post heart transplant for recalcitrant rejection - A single centre experience.
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Lee Felicity, Clare Fazackerley B N, Lim Tee S, D'Orsogna Lloyd, Downing Jon, Truong Linh, Shah Amit, Baumwol Jay, Lam Kaitlyn, Lambert James, Dias Peter, Njue Faith, Dembo Lawrence
Аннотация
BACKGROUND: A previous small study (2007) of patients who received short-course, low-dose total lymphoid irradiation (sTLI) as treatment for recalcitrant cardiac rejection post-heart transplantation (HTx) reported good treatment compliance without significant toxicities and improvement in rejection frequency. We conducted a retrospective analysis, evaluating longer-term outcomes in this patient cohort.
METHODS AND RESULTS: We reviewed the medical records of 21 HTx recipients (mean age ± std. 43.7 ± 12.8 years; 47.6 % female) who received sTLI between 2001 and 2023. Five patients were highly sensitized pre-HTx (calculated panel-reactive antibody >80 %) and 8 patients received induction immunosuppression at time of HTx. Patients received 4.5Gy in four fractions over 4 consecutive days administered (n = 13 as an outpatient), at a median of 442 (IQR 47-966) days post-HTx. STLI was well-tolerated symptomatically with no persistent lymphopenias. Eleven patients had no further rejection. Ten patients had immediate rejection resolution with later rejection detected (median 401 [IQR 301-1569] days post-sTLI). Thirteen patients, mostly transplanted pre-2010, have deceased (median graft survival 7.6 years, mean follow-up 9.4 years). One patient died of metastatic colon cancer. There were no haematological malignancies. Two patients received a second sTLI course and subsequent re-HTx.
CONCLUSIONS: We report the largest case series of patients who received sTLI post-HTx. STLI is well-tolerated, with resolution of immediate recalcitrant rejection in all patients and resolution of rejection in the longer term in 52 %. STLI is a possible alternative option for patients with cardiac rejection refractory to routine, augmented immunotherapy. Further larger studies are required to assess the longer-term efficacy and safety of this treatment.
METHODS AND RESULTS: We reviewed the medical records of 21 HTx recipients (mean age ± std. 43.7 ± 12.8 years; 47.6 % female) who received sTLI between 2001 and 2023. Five patients were highly sensitized pre-HTx (calculated panel-reactive antibody >80 %) and 8 patients received induction immunosuppression at time of HTx. Patients received 4.5Gy in four fractions over 4 consecutive days administered (n = 13 as an outpatient), at a median of 442 (IQR 47-966) days post-HTx. STLI was well-tolerated symptomatically with no persistent lymphopenias. Eleven patients had no further rejection. Ten patients had immediate rejection resolution with later rejection detected (median 401 [IQR 301-1569] days post-sTLI). Thirteen patients, mostly transplanted pre-2010, have deceased (median graft survival 7.6 years, mean follow-up 9.4 years). One patient died of metastatic colon cancer. There were no haematological malignancies. Two patients received a second sTLI course and subsequent re-HTx.
CONCLUSIONS: We report the largest case series of patients who received sTLI post-HTx. STLI is well-tolerated, with resolution of immediate recalcitrant rejection in all patients and resolution of rejection in the longer term in 52 %. STLI is a possible alternative option for patients with cardiac rejection refractory to routine, augmented immunotherapy. Further larger studies are required to assess the longer-term efficacy and safety of this treatment.