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P6.21 Effectiveness of antibody-removal therapy in pediatric intestinal transplant recipients

Ane M Andres, Spain

Pediatric Transplant Surgeon
Pediatric Surgery
Hospital La Paz


Effectiveness of antibody-removal therapy in pediatric intestinal transplant recipients

Maria Lasa1,2, Esther Ramos3,4, Esther Mancebo1,2, María José Castro-Panete1, Daniel Pleguezuelo1, Pilar Serrano3, Ane Miren Andrés4,5, Francisco Hernández4,5, Estela Paz-Artal1,2, Paloma Talayero1,2.

1Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain; 2imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain; 3Unit of Intestinal Rehabilitation and Transplant, University Hospital La Paz, Madrid, Spain; 4IdiPaz Research Institute, University Hospital La Paz, Madrid, Spain; 5Department of Pediatric Surgery, University Hospital La Paz, Madrid, Spain

Introduction: Donor specific anti-HLA antibodies (DSA) impact negatively on the intestinal transplant (IT) outcome.  Although the use of antibody-removal therapies (ART) is becoming more frequent in the last years, issues as “when and how” still remain under discussion especially when they are detected in the absence of any clinical symptom.
In the present study we perform an analysis of the ART experience in our pediatric cohort, reporting the different indications and the possible factors that may influence on the treatment success.
Methods: We studied retrospectively a cohort of 114 IT. 13 ART procedures in 10 transplants were carried out. Desensitization was performed with different combinations of intravenous immunoglobulin, plasmapheresis and rituximab. Anti-HLA antibodies were tested by Luminex assay.
Results: DSA were confirmed in 20 transplants. ART was performed in 10 of them (Table 1). Three recipients were desensitized peritransplant because of preformed DSA. Another 3 were treated in the context of rejection while 4 more were desensitized when DSA appearance without rejection. In one case rituximab was used for PTLD treatment.
Complete DSA negativization was observed in 7/13 procedures, while in another 2, DSA against HLA-class I but not class II were cleared (Table 1). Global anti-HLA antibodies decreased in another patient although DSA persisted but with lower intensity. In 3 procedures (all of them corresponding to P3) no changes were observed. Thus, considering both DSA negativization and DSA decrease (either in intensity or number of specificities) as successful outcomes, ART showed to be effective in the 77% of the procedures (10/13) and 80% of transplants (8/10).

Analyzing the impact of DSA MFI on the therapy outcome, we observed it was significantly higher in persistent DSA than in cleared DSA (p=0.017). Another factor that showed to be relevant for the treatment success was the time between DSA detection and desensitization starting, this being significantly lower for cleared DSA (p=0.025).
The 8-years allograft survival in desensitized recipients was similar to those without DSA. Nevertheless, non-desensitized patients with DSA showed significantly lower graft survival (p=0.003) (Figure 2). No rejection was observed after treatment in 60% of transplants. Regarding other complications, 7/10 transplants did not develop any adverse event, 2 suffered CMV infection (1 de novo and 1 reactivation) and 1 suffered from catheter associated bacteremia.

Conclusion: ART in IT pediatric recipients resulted effective in 80% of the transplants, showing these patients a long-term allograft survival similar to the DSA negative group and higher than in non-desensitized DSA+ recipients.
MFI and time elapsed until the beginning of the desensitization procedure were the most relevant factors determining the outcome. These results encourage the use of ART as soon as DSA are detected, even in the absence of clinical symptoms.