Evaluation of serial monitoring of donor-specific antibodies in pediatric and adult intestinal/multivisceral transplant recipients.

BACKGROUND: The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring. METHODS: This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed. RESULTS: Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II. CONCLUSION: Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.

Valganciclovir for the treatment of cytomegalovirus infections in pediatric intestinal transplant recipients: A case series.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection post-transplant and is associated with significant morbidity and mortality. Currently, there are no FDA dosing recommendations for the use of valganciclovir for the treatment of CMV infections in pediatric patients. This case series describes the use of valganciclovir for the treatment of CMV infections in nine pediatric intestinal transplant recipients (pITR). METHODS: Retrospective review of pITR between January 2004 and December 2016. The primary outcome was resolution of CMV viremia. Secondary outcomes included time-to-resolution of viremia, relapse rate, incidence of resistance, hematologic adverse effects, rejection, graft loss, and death. RESULTS: Of 214 pITR, ten CMV infections were treated with valganciclovir. One patient was lost to follow-up while on treatment and was not included. Eight (89%) patients had resolution of CMV viremia. The average dose of valganciclovir was 14.3mg/kg (SD 0.82) twice daily. CMV resistance testing was completed in three (33.3%) patients; one patient had a documented mutation requiring leflunomide to clear viremia. Three (33.3%) patients experienced rejection within one month prior to or during treatment for CMV. Six (66.6%) experienced hematologic side effects. No patients died or experienced graft loss. CONCLUSION: This is the first study to assess the use of valganciclovir for the treatment of CMV in pITR. Based on these results, weight-based dosing of valganciclovir seems to be an appropriate option for the treatment of CMV in pITR. Given limited number of patients reviewed in this case series and the high incidence of hematologic side effects, further investigation is warranted.

Viral enteritis in intestinal transplant recipients.

Intestinal transplant recipients (ITR) are at high risk for infections due to the high level of immunosuppression required to prevent rejection. There are limited data regarding viral enteritis post-intestinal transplantation. We retrospectively reviewed ITR transplanted between January 2008 and December 2016. Descriptive statistics, including mean (standard deviation) and median (range), were performed. Sixty-one (43.9%) of the 139 transplanted patients had viral enteritis: 26% norovirus, 25% adenovirus, and 9% each rotavirus and sapovirus. The median age of pediatric patients was 1.6 years (0.4-16.9) and for adults 36.3 years (27.1-48.2). Fifty-seven (58%) of 99 pediatric ITR had viral enteritis compared to 4 (10%) of 40 adult ITR. Median time-to-clinical resolution of enteritis for all patients was 5 days (1-92). Standard of care therapies administered: anti-motility agents (10%), anti-emetics agents (14%), and intravenous fluids (42%). There was a higher incidence of viral enteritis in pediatric compared to adults ITR. The majority of viral enteritis episodes resolved within 1 week and were treated with supportive therapy.