Fatal GvHD as a complication of liver transplantation for undetermined fulminant hepatic failure and associated aplastic anemia

Abstract

Fulminant hepatic failure of unknown origin is the most common cause of fulminant hepatitis with high incidence of aplastic anaemia. Furthermore, the association of liver failure and aplastic anaemia has an increased mortality rate. In this report we describe a 16-month-old boy who presented with aplastic anaemia preceding a non-A, non-B, non-C fulminant liver failure. He developed severe graft versus host disease (GvHD) after liver transplantation, proven by the presence of donor cells in the peripheral blood and in the skin biopsy. He received conventional therapy (steroids, mycophenolate, anti-IL-2 monoclonal antibodies, anti-thymocyte globulin) without success. In an attempt to obtain T cell depletion and reduce the GvHD, he was treated with Alemtuzumab, a first time use for this indication. Aplastic anaemia was extensively investigated, especially exploring the possibility of primary immunodeficiency and reticular dysgenesis which were excluded based on clinical history. However, another form of primary immunodeficiency could be the cause of the uncontrollable proliferation of the donor lymphocytes derived from the liver transplant. Despite aggressive treatment GvHD progressed and the patient died of multiorgan failure. The majority of authors mention aplastic anaemia as a secondary event post liver transplant, whereas in our view this might be a haematopoietic stem cell disorder preceding fulminant hepatic failure. These patients also need to be evaluated extensively in order to exclude a primary immunodeficiency. The underlying disease will determine the choice of immunosuppressive treatment, especially in case of development of GvHD caused by the transplanted lymphocytes inhabiting the donor liver.

Severe autoimmune hemolytic anemia in a liver transplanted child

“…HA is a rare but severe complication of bone marrow and solid organ transplantation (1–3). It can be the result of GVH disease due to mixed/partial chimerism, persistence of donor lymphocytes in the allograft (8), or immunosuppressive drugs (9, 10), causing a microangiopathic hemolytic process (7). In our case, GVH disease was excluded as our patient and the liver donor were HLA 6/6 identical (8, 9) and the liver biopsy showed no GVH findings.…”

“…It can be the result of GVH disease due to mixed/partial chimerism, persistence of donor lymphocytes in the allograft (8), or immunosuppressive drugs (9, 10), causing a microangiopathic hemolytic process (7). In our case, GVH disease was excluded as our patient and the liver donor were HLA 6/6 identical (8, 9) and the liver biopsy showed no GVH findings. Because of potential drug toxicity, tacrolimus was immediately replaced by cyclosporine (1, 2).…”

Graft‐versus‐host disease in paediatric solid organ transplantation: A review of the literature

“…A summary of individual cases detailed in both the case reports and the case series can be seen in Tables 1 and 2, respectively (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). The most common presenting symptom is a maculopapular rash, which was found in 87% of patients.…”

“…DZB has been used in two case reports without success . Infliximab, a TNF‐α receptor inhibitor, was used in four cases reports in combination with a number of other biologics and steroids.…”

“…While depletion of T cells is thought to increase the risk of infectious complications, a number of patients have been treated with ATG. There are three cases in the literature, of which two had uncontrolled disease and the third died following the development of septic shock .…”