Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance

Abstract

A 2-year-old boy underwent liver transplantation for fulminant hepatic failure of unknown cause. Four months later the child developed severe aplastic anemia. Allogeneic bone marrow transplantation (BMT) was performed using marrow from his 14-month-old HLA-identical sister. Severe aplastic anemia recurred 2.5 months later. After reconditioning a second BMT was performed using the same donor. Tapering of immunosuppression 2 years after BMT led to biopsy-confirmed rejection of the liver. Therapy with high-dose corticosteroids and an increase in cyclosporine A medication readily reversed rejection and a low-dose immunosuppression reflected by cyclosporine trough levels less than 50 ng/ml has been maintained since. Eight years later the boy is in excellent health with both bone marrow and liver functioning perfectly. In summary, this case demonstrates that even recurrent severe aplastic anemia after OLT can be cured by BMT, and that a transplanted liver can tolerate a double conditioning regimen without problems. Tolerance towards the liver through BMT did not develop.

Acute graft versus host disease after orthotopic liver transplantation

“…This infusion of immunocompetent cells and pluripotent progenitors, in conjunction with the immunosuppression used for the liver transplant, resembles the circumstances of an immunosuppressed patient receiving a hematopoietic stem cell transplant. In fact, donor lymphocytes can be routinely found within three weeks and even up to 100 days after OLT in the peripheral blood and bone marrow [12,13], and detectable chimerism is associated with a decreased risk of liver rejection. In most cases, over time the immune system of the patient rejects the donor’s lymphocytes and full host chimerism is re-established.…”

Tolerance to liver allograft after allogeneic hematopoietic cell transplantation for severe aplastic anemia from the same HLA-matched sibling donor

“…One patient developed acute GVHD and mild liver rejection while on CYA and prednisone, 4 another developed rejection during IST tapering. 8 Our case is unique in its use of the same donor for LT and HCT for SAA, which permitted successful IST withdrawal and donorspecific tolerance through the induction of hematopoietic chimerism. In the non-SAA setting, there have been two case reports of allograft tolerance following living-related LT and HCT from the same donor: a 4-month-old girl underwent LT followed by haploidentical HCT from her mother for familial hemophagocytic lymphohistiocytosis, 13 and a 41-year-old man received an HCT for ALL followed by a LT from the same matched sibling donor for cholangiocarcinoma.…”

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

“…The association between non‐A‐E fulminant hepatitis and SAA was first noted in 1955, with more recent investigations noting an incidence of SAA complicating 33% of hepatic transplants for this indication . SAA associated with hepatitis has a high mortality rate and is felt to be likely secondary to abnormal immunological activation.…”