The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation Following Liver Transplantation in Children with Immunodeficiencies

Background: Case reports of allogeneic hematopoietic stem cell transplantation (HSCT) following liver transplantation in children with immunodeficiencies have been published in the past and have described correction of the underlying disease.

The objective of this study is to report the clinical outcomes of a series of pediatric recipients of allogeneic hematopoietic stem cell transplantation following previous liver transplantation.

Method: Retrospective analysis of 8 patients who underwent HSCT following previous liver transplantation between 2003-2012 at a single institution.

Results: Seven patients (4 males and 3 females) underwent orthotopic whole liver transplantation for fulminant or chronic liver disease of unknown etiology; 1 male patient received segmental liver transplantation for alpha-1 antitrypsin deficiency. Six of 8 patients underwent reduced intensity conditioning while 2/8 received myeloablative conditioning prior to allogeneic hematopoietic stem cell transplantation. Seven patients received unrelated donor HSCT and 1 patient had a matched sibling donor. Seven patients were later diagnosed with hemophagocytic lymphohistiocytosis (HLH), 5/7 with negative genetic studies for known genes of HLH, including one with Epstein Barr Virus-induced HLH, 1 patient with X-linked inhibitor of apoptosis deficiency-induced HLH, 1 patient with combined immune deficiency. All patients engrafted. Two patients died before day 100, 1 patient has been lost of follow up more than 2 years after HSCT, 4 patients are alive for +3 years with good life quality, and one patient has recently been transplanted. Two patients with mild or no transaminitis still receive low dose of immune suppressive drugs for liver transplant as directed by their surgeons.

Conclusion: HLH may present with fulminant or cryptogenic liver failure requiring correction with orthotopic liver transplantation prior bone marrow transplantation. Orthotopic liver transplantation followed by unrelated donor HSCT using reduced intensity conditioning can lead to relevant immune reconstitution with stably improved quality of life and resolution of HLH.