Agustina Zambernardi¹, Ana Cabanne², Pedro Gonzalez², Martín Rumbo³, Ana Chiodetti³, Juan Manuel Padín¹, Carolina Rumbo¹, Gabriel Gondolesi¹

¹Instituto de Trasplante Multiorganico - Programa de Inmunobiología e Investigación Traslacional en Trasplante, Hospital Universitario - Fundación Favaloro, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina; ²Anatomia Patologica, Hospital Universitario - Fundación Favaloro, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina; ³Laboratorio de Investigaciones del Sistema Inmune, Facultad de Ciencias Exactas Universidad Nacional de La Plata, La Plata , Buenos Aires, Argentina

Introduction: Different factors such as pre-transplant immunological risk (IR), degree of ischemia reperfusion injury (IRI) and immunosuppression scheme have been associated with an increase risk for early acute cellular rejection (EACR) after intestinal transplant (ITx). The relationship between the immediate post ITx clinical outcome and EACR risk has been proposed but seldom documented. Our aim was to analyze the impact of initial adverse clinical events in the occurrence of EACR (1st month) in our cohort of patients.

Material and Methods: Retrospective analysis of 23 isolated and combined ITx performed between 3-2006 and 2-2011. Variables: Total ischemia time (TIT)/Warm ischemia time (WIT), IRI (Park Index and MDA histochemistry), IR, induction and maintenance immunosuppression (IS), achievement of drug target level (ATL), incidence of EACR (mild, moderate and severe), surgical complications (SC) and severe infectious complications (IC), overall rejection free and patient survival. Patientswere divided into 3 groups:Group 1: IC + SC (n = 10); Group 2: SC (n = 5) and Group 3 no-complications (n = 8).

Results: TIT/WIT, IRI, ISaccording to IR could not be associated with the occurrence of EACR. Adverse clinical outcome showed a clear association with EACR (9/10 in group 1; 3/5 in group 2; 1/8 in group 3, p=0.0015). Non ATLwas associated with EACR: 5/5 in group 1 (all severe), 3/5 in group 2 (all mild). However, patients with optimal ATL also presented ACR: 4/5 (all mild) in group 1 and 1/8 (mild) in group 3. (p=NS).Among patients who underwent severe EACR (n=5), 3/5 were treated and recovered (only one of them presented 2 new episodes of mild ACR in 5 years of follow up) and 2/5 died with concomitant severe CMV infection. Therejection-free survivalwas significantly lower (p<0.02) in group 1 (95% CI 12-45 days) than group 3 (95% CI 55-856 days). Patient survival at 950 days of follow-up (overall mean survival time) was 70% group 1, 80% group 2 and 100% group 3 (p=NS).

Conclusion: 1- IC hasbeen the most important risk factor to develop EACR, even in patients with optimal IS level.  2- Decreased levels of IS in patients with severe infection was associated with high risk to evolve to severe EACR. 3- If timely diagnosed severe EACR could be successfully treated. 4- In our cohort occurrence of EACR did not impact on long term patient survival or graft loss.