Acute hepatic failure as onset of progressive sclerodermatous chronic graft-versus-host disease after donor lymphocyte infusion

Abstract

We report a patient who underwent allogeneic haematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI), and later developed acute hepatic failure followed by progressive chronic sclerodermatous graft-versus-host disease (GVHD).A 28-year-old man with acute myelogenous leukaemia (AML) underwent allogeneic HSCT from his HLA-identical brother in July 2002, in first complete remission. The conditioning regimen consisted of busulphan and cyclophosphamide. Cyclosporin A (CyA) and a short course of methotrexate were given for GVHD prophylaxis. Peripheral blood stem cells containing 4.4 Â 10 6 /kg CD34 cells and 1 Â 10 7 /kg CD3 cells were infused on day 0. Neutrophil engraftment (40.5 Â 10 9 /l) occurred on day þ 12 and platelet engraftment (420 Â 10 9 /l) on day þ 21. AML relapse occurred 5 months after HSCT, and CyA was discontinued. The disease was resistant to three courses of chemotherapy and only Ara-C by continuous infusion for 20 days was effective. At the beginning of May 2003, the patient received the first DLI at 2.5 Â 10 7 /kg CD3. After 1 month, complete chimaerism was observed in bone marrow and peripheral blood. On day þ 20 after DLI, the patient developed a grade III acute GVHD involving the skin and liver, which was treated with methylprednisolone, tapered after 3 weeks. A second DLI with 2.5 Â 10 7 /kg CD3 was given at the end of July 2003, when the patient did not show any sign of GVHD and was off immunosuppression. On day þ 41, chronic GVHD with mouth and liver involvement developed. This was confirmed by liver biopsy, which also showed grade IV haemosiderosis (Searle grading). Liver function tests showed ALP 312 IU/l, g-GTP 158 IU/l, AST 144 IU/l and ALT 198 IU/l. Total bilirubin, albumin, prothrombin time and cholinesterase were normal (Table 1). The IgG serum level was 1521 mg/dl, and hepatitis A, B and C markers were negative. CMV antigenaemia test and RT-PCR for serum HCV, HBV, EBV, HH6, VZV and HSV were negative. The titer of anti-nuclear antibody was 1:80. Other autoimmune markers were negative. Chronic GVHD involving the skin, with areas of hypo-and hyperpigmentation in the back and in the abdomen, developed on day þ 71 and was not treated. At 105 days after the second DLI, the patient developed oedema of the extremities, ascites and pleural effusion, with decreased levels of albumin (24 g/l) and cholinesterasis (2721 IU/l) and increased prothrombin time (40 s). Transaminases and cholestatic enzymes were stable, except for an increase of ALP (420 U/l); total bilirubin remained normal. RT-PCR for serum HCV, HBV, EBV, HH6, VZV and HSV, and CMV antigenaemia test were