Living-Donor Liver Transplantation for Chronic Hepatic Graft-versus-Host Disease
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In 2002, a four-year-old boy who had been diagnosed with acute lymphoblastic leukemia in 1999 received a bone marrow transplant from his mother, who had three HLA-antigen mismatches and an incompatible blood type. After engraftment, an erythematous rash, diarrhea, and hepatomegaly, accompanied by elevated liver-enzyme levels, developed in the boy. The findings were indicative of acute graft-versus-host disease (GVHD) and led to intensified immunosuppressive therapy with mycophenolate mofetil and corticosteroids. Although the gut and skin GVHD improved, the hepatic GVHD persisted and was confirmed as chronic hepatic GVHD on liver biopsy (Figure 1A and Figure 1B). The chronic GVHD was managed with low-dose corticosteroids, because of persistent hyperbilirubinemia, elevated liver-enzyme levels, thrombocytopenia, and coagulopathy. After transplantation, the patient showed complete engraftment of the transplanted bone marrow (99 percent). Bone marrow biopsy and other investigations showed no evidence of the relapse of leukemia. In March 2005, the boy underwent living-donor liver transplantation from his mother, because no other donor candidate was available.1 The left-lobe graft weighed 270 g, and the graft-to-recipient weight ratio was 1.0 percent. Both the portal vein and hepatic artery of the graft were flushed with muromonab-CD3 (Orthoclone OKT3, Ortho Pharmaceutical) that was contained in a histidine–tryptophan–ketoglutarate solution to wash out and eliminate donor lymphocytes. Histopathological examination of the boy's explanted liver revealed the presence of ductopenia with foam-cell arteriopathy, which was consistent with chronic hepatic GVHD (Figure 1C and Figure 1D).
Figure 1. Liver-Biopsy Specimens from a Patient with Chronic Graft-versus-Host Disease (GVHD).
Panels A and B show ductopenia and hepatocanalicular cholestasis (hematoxylin and eosin), Panel C shows ductopenia (hematoxylin and eosin), and Panel D shows foam-cell arteriopathy (Masson trichrome). In Panel E, the hepatocytes in the post–transplantation-protocol biopsy appear to be almost normal, without evidence of either rejection or GVHD (hematoxylin and eosin).
Postoperative immunosuppression consisted of low-dose tacrolimus and corticosteroids to prevent GVHD. The patient was discharged on postoperative day 31 without complications. Protocol liver biopsy on postoperative day 60 revealed no evidence of rejection or GVHD (Figure 1E). During eight months of follow-up, the patient has been doing well with normal liver function.
GVHD, a major cause of liver dysfunction after bone marrow transplantation, occurs in 60 to 80 percent of patients when marrow from a partially HLA-matched family donor or unrelated donor is used.2 Because the patient showed no involvement of gut or skin in the GVHD and GVHD treatment had failed, he was considered a candidate for replacement of the liver. Given host immunosuppression related to bone marrow transplantation, the risk for passenger lymphocyte–associated GVHD may be an additional complication.3,4 Additional measures were required to avoid allogeneic reactions arising from passenger lymphocytes in the graft. We used a left-lobe graft, which provided the minimum graft-to-recipient weight ratio (1.0 percent) needed to sustain metabolic demand in the recipient5 and muromonab-CD3 to reduce the number of donor-derived passenger lymphocytes. This case offers evidence that a living-donor liver transplant can be harvested from the same donor who provided bone marrow for transplantation and that the recipient can be successfully treated with surgical and immunologic innovations.
Tetsunosuke Shimizu, M.D.
Mureo Kasahara, M.D.
Koichi Tanaka, M.D.
Kyoto University
Kyoto 606-8507, Japan
sur116@poh.osaka-med.ac.jp
References
Andreoni KA, Lin JI, Groben PA. Liver transplantation 27 years after bone marrow transplantation from the same living donor. N Engl J Med 2004;350:2624-2625.
Figuera A, Tomas JF, Otero MJ, Moreno E, Garcia I, Fernandez-Ranada JM. Orthotopic liver transplantation for acute grade IV hepatic graft-versus-host disease following bone marrow transplantation. Am J Hematol 1996;52:68-69.
Mackinnon S, Papadopoulos EB, Carabisi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 1995;86:1261-1268.
Schlitt HJ, Raddatz G, Steinhoff G, Wonigeit K, Pichlmayr R. Passenger lymphocytes in human liver allografts and their potential role after transplantation. Transplantation 1993;56:951-955.
Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999;67:321-327.
Figure 1. Liver-Biopsy Specimens from a Patient with Chronic Graft-versus-Host Disease (GVHD).
Panels A and B show ductopenia and hepatocanalicular cholestasis (hematoxylin and eosin), Panel C shows ductopenia (hematoxylin and eosin), and Panel D shows foam-cell arteriopathy (Masson trichrome). In Panel E, the hepatocytes in the post–transplantation-protocol biopsy appear to be almost normal, without evidence of either rejection or GVHD (hematoxylin and eosin).
Postoperative immunosuppression consisted of low-dose tacrolimus and corticosteroids to prevent GVHD. The patient was discharged on postoperative day 31 without complications. Protocol liver biopsy on postoperative day 60 revealed no evidence of rejection or GVHD (Figure 1E). During eight months of follow-up, the patient has been doing well with normal liver function.
GVHD, a major cause of liver dysfunction after bone marrow transplantation, occurs in 60 to 80 percent of patients when marrow from a partially HLA-matched family donor or unrelated donor is used.2 Because the patient showed no involvement of gut or skin in the GVHD and GVHD treatment had failed, he was considered a candidate for replacement of the liver. Given host immunosuppression related to bone marrow transplantation, the risk for passenger lymphocyte–associated GVHD may be an additional complication.3,4 Additional measures were required to avoid allogeneic reactions arising from passenger lymphocytes in the graft. We used a left-lobe graft, which provided the minimum graft-to-recipient weight ratio (1.0 percent) needed to sustain metabolic demand in the recipient5 and muromonab-CD3 to reduce the number of donor-derived passenger lymphocytes. This case offers evidence that a living-donor liver transplant can be harvested from the same donor who provided bone marrow for transplantation and that the recipient can be successfully treated with surgical and immunologic innovations.
Tetsunosuke Shimizu, M.D.
Mureo Kasahara, M.D.
Koichi Tanaka, M.D.
Kyoto University
Kyoto 606-8507, Japan
sur116@poh.osaka-med.ac.jp
References
Andreoni KA, Lin JI, Groben PA. Liver transplantation 27 years after bone marrow transplantation from the same living donor. N Engl J Med 2004;350:2624-2625.
Figuera A, Tomas JF, Otero MJ, Moreno E, Garcia I, Fernandez-Ranada JM. Orthotopic liver transplantation for acute grade IV hepatic graft-versus-host disease following bone marrow transplantation. Am J Hematol 1996;52:68-69.
Mackinnon S, Papadopoulos EB, Carabisi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 1995;86:1261-1268.
Schlitt HJ, Raddatz G, Steinhoff G, Wonigeit K, Pichlmayr R. Passenger lymphocytes in human liver allografts and their potential role after transplantation. Transplantation 1993;56:951-955.
Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999;67:321-327.