Abstract

Introduction: Exfoliative rejection (ER) following small bowel or combined liver/small bowel transplantation is an extreme form of graft rejection associated with significant morbidity and mortality with high rates of allograft removal. Re-transplantation after exfoliative rejection has demonstrated low success rates. During the outset of rejection episodes, few predictors differentiate between ER and non-exfoliative rejection. Aggressive immunosuppression with antibody based therapy and early surgical intervention remain the cornerstone of management. Our treatment protocol for acute cellular rejection requires failure of a steroid burst before antithymocyte antibodies are started, but excessive delay in initiation of antibody therapy may result in exfoliation and graft loss. Our objective is to determine if peripheral blood lymphocyte counts can predict progression to ER. Methods: All patients undergoing a small bowel or combined liver/small bowel transplant at Cincinnati Children’s Hospital Medical Center (CCHMC) were retrospectively reviewed for this study. All with biopsy proven acute cellular rejection and peripheral blood lymphocyte enumeration were included. The histologic severity of the rejection episode and lymphocyte counts prior to and during the rejection episode were collected. Results: Electronic medical record changes permitted review of 38 of 55 transplants since 2003. Twenty-nine patients (76%) had histologic rejection greater than Grade 1. Of all patients, 5 (13%) had ER. Early biopsies eventually progressing to ER had higher peripheral blood absolute lymphocyte counts (ALC) prior to rejection than did biopsies diagnostic of rejection failing to progress (960 vs 600, p = 0.02). More importantly, peripheral blood lymphocyte counts also rose much more dramatically in those whose biopsies subsequently progressed to exfoliation than in those whose rejection did not progress (1179% vs 81%, p <0.001). Conclusion: Based on these data, absolute lymphocyte count, specifically, the variance in ALC is associated with progression from low grade rejection to ER. Although, there was a statistically significant difference in the ALC in patients with exfoliation, substantial variance from baseline may be more important than the absolute number in predicting ER, thereby justifying early use of antithymocyte globulin or alemtuzumab.

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