Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion.

Graft-versus-host disease (GVHD) of the liver is characterized by bile duct damage and portal lymphocytic infiltrate. We report acute hepatitislike presentation of GVHD after donor lymphocyte infusion (DLI). Between April 1998 and September 2001, 73 patients received 94 DLI treatments. Liver GVHD developed after DLI in 22 (30%) patients whose median age was 43 years (range, 21 to 61 years). Onset of liver dysfunction was at 35 days (range, 11 to 406 days) after DLI. Fifteen patients underwent liver biopsy, and the diagnosis of liver GVHD was confirmed in 13 (87%) patients. After viral hepatitis and recent drug exposure were excluded, 11 (50%) patients were given a diagnosis of a hepatitic variant of GVHD based on histologic evidence of lobular hepatitis (n = 5), elevation of maximum serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level more than 10 times the upper normal limit (n = 9), or both. There was a significant difference in maximum ALT (P =.002) and AST (P =.01) level between the hepatitic-variant and classical GVHD groups. GVHD progressed in 14 (64%) patients, and 10 patients died after a median follow-up of 221 days (range, 31-1284 days). These observations suggest that GVHD that occurs after DLI may have distinct clinical features. Hepatitic-variant GVHD should be considered in the differential diagnosis in DLI recipients with unexplained hepatitis.

[1]  T. Braun,et al.  Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  D. Green,et al.  Accumulation and Activation-Induced Release of Preformed Fas (CD95) Ligand During the Pathogenesis of Experimental Graft-Versus-Host Disease1 , 2001, The Journal of Immunology.

[3]  J. Gribben,et al.  T-cell--depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect. , 2001, Blood.

[4]  M. Ohtsuki,et al.  Therapeutic effect of novel anti-human Fas antibody HFE7a on graft-versus-host disease model. , 2001, Clinical immunology.

[5]  K. Takenaka,et al.  Hepatic graft-versus-host disease presenting as an acute hepatitis after allogeneic peripheral blood stem cell transplantation , 2001, Bone Marrow Transplantation.

[6]  M. Flowers,et al.  Chronic graft‐versus‐host disease of the liver: Presentation as an acute hepatitis , 2000, Hepatology.

[7]  J. Serody,et al.  T-lymphocyte production of macrophage inflammatory protein-1α is critical to the recruitment of CD8+ T cells to the liver, lung, and spleen during graft-versus-host disease , 2000 .

[8]  E. Ball,et al.  Hematopoietic Stem Cell Therapy , 2000 .

[9]  G. Hill,et al.  The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. , 2000, Blood.

[10]  K. Matsushima,et al.  Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease. , 1999, The Journal of clinical investigation.

[11]  K. Oshimi,et al.  Differential Effects of Anti-Fas Ligand and Anti-Tumor Necrosis Factor α Antibodies on Acute Graft-Versus-Host Disease Pathologies , 1998 .

[12]  G. Hill,et al.  The role of cytokines in acute graft-versus-host disease. , 1997, Cytokines, cellular & molecular therapy.

[13]  C. Howell,et al.  Contributions of donor CD4 and CD8 cells to liver injury during murine graft-versus-host disease. , 1996, Transplantation.

[14]  R. Storb,et al.  A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. , 1990, Blood.

[15]  W. Yasmineh,et al.  Serum 5'nucleotidase and alkaline phosphatase--highly predictive liver function tests for the diagnosis of graft-versus-host disease in bone marrow transplant recipients. , 1989, Transplantation.

[16]  Pankaj Sharma,et al.  A coded histologic study of hepatic graft‐versus‐host disease after human bone marrow transplantation , 1988, Hepatology.

[17]  K. Sullivan,et al.  Intestinal and hepatic complications of human bone marrow transplantation. Part I. , 1986, Gastroenterology.

[18]  J. Boitnott,et al.  Pathology of the liver with bone marrow transplantation. Effects of busulfan, carmustine, acute graft-versus-host disease, and cytomegalovirus infection. , 1980, The American journal of pathology.

[19]  J. Cavenagh,et al.  Myositis, polyserositis with a large pericardial effusion and constrictive pericarditis as manifestations of chronic graft-versus-host disease after non-myeloablative peripheral stem cell transplantation and subsequent donor lymphocyte infusion , 2001, Bone Marrow Transplantation.

[20]  William M. Lee,et al.  Chronic graft-versus-host disease after hematopoietic cell transplantation presenting as an acute hepatitis , 2001, American Journal of Gastroenterology.

[21]  M. Bonamino,et al.  Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease , 2001, Bone Marrow Transplantation.

[22]  J. Serody,et al.  T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease. , 2000, Blood.

[23]  K. Oshimi,et al.  Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies. , 1998, Blood.

[24]  K. Sullivan,et al.  A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. , 1990, Blood.

[25]  D. Snover,et al.  Hepatic Graft Versus Host Disease: A Study of the Predictive Value of Liver Biopsy in Diagnosis , 1984, Hepatology.