Kidney transplant after hematopoietic cell transplant in pediatrics: Infectious and immunosuppressive considerations

Abstract

Pediatric patients requiring kidney transplant after hematopoietic cell transplant receive multiple courses of immunosuppression placing them at risk for infection. To elucidate potential risk factors for infection, we compared the immunosuppressive regimens and infectious complications of pediatric kidney transplant recipients at a single institution who had previously undergone hematopoietic cell transplant from different donors to similar patients reported in the literature. Among the initial four post-hematopoietic cell transplant kidney transplant patients reviewed, viremia episodes were universal, including BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from presumed BK virus encephalitis. No viremia was reported in five similar cases in the literature. Risk factors for increased infection include use of lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune reconstitution time between transplants, increased pre-KTx viral burden, and use of T-cell-depleting versus -suppressive induction immunosuppression for KTx. These findings suggest that pediatric post-HCT KTx recipients are at increased risk for viral infections, likely benefitting from thorough pre-KTx evaluation of immune reconstitution and preferential use of non-T-cell-depleting induction therapy for KTx. We applied these recommendations to one subsequent post-HCT patient requiring KTx at our institution with excellent outcomes one year post-KTx.

Sequential transplantation and implications for clinical management: OLT followed by HCT and consequent RT in a pediatric patient

“…Similar to studies in the post‐SOT population, there has been most notable decline of renal function in the first year post‐HCT, with relative stabilization of renal function following . If progression to ESRD is noted, average time between HCT and RT has been reported to be between 3.2 and 5 years . Significantly less data exists in regard to CNI‐sparing protocols in the post‐HCT time frame, although sirolimus use is incorporated into some protocols .…”

“…The most common complication following tandem transplantations has been viral reactivation and significant (sometimes lethal) viral disease from increased immunosuppression requirement . This patient did experience complications of adenoviremia that was identified quickly, preventing significant morbidity and mortality.…”

“…The incidence of CKD in HCT is variably reported, ranging up to a reported 20%‐ 50% range in children . While incidence of CKD is variably defined, the incidence of ESRD is even more poorly defined, due to rarity and reliance on case reports .…”

“…Advancements in graft manipulation, such as αβ T‐cell depletion may lead to accelerated immunologic recovery and decreasing needs for prolonged immunosuppression . There have been favorable outcomes noted in the adult population undergoing RT after HCT, but outcomes in pediatric recipients have not been well studied—though case reports of successful RT ation exist …”

“…Due to rarity of sequential transplants in the pediatric population, numerous questions remain in regard to management of immunosuppression throughout these processes. It is unclear how the process of immune reconstitution and development of tolerance after HCT could affect a past and future SOT . Little data are available on the HLA constitution and compatibility of prior solid organ graft donors with hematopoietic cell donors and potential for “graft vs graft disease” .…”