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

Bone Marrow Transplantation volume 35, pages 523–524 (2005)Cite this article

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 × 106/kg CD34 cells and 1 × 107/kg CD3 cells were infused on day 0. Neutrophil engraftment (>0.5 × 109/l) occurred on day +12 and platelet engraftment (>20 × 109/l) on day +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 × 107/kg CD3. After 1 month, complete chimaerism was observed in bone marrow and peripheral blood. On day +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 × 107/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 +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, γ-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 +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 negative. The levels of gamma-globulin (IgG 2069 mg/dl, polyclonal) and anti-nuclear antibody (1:2560) increased. Echography and Doppler sonography showed ascites without any other alteration. Liver biopsy was repeated but it did not confirm or exclude liver GVHD because of the inadequate sample. Therapy with albumin and intravenous (i.v.) diuretics was started. Sclerodermatous changes in the forearms and lower legs became evident as the oedema diminished. CyA was given at a dose of 1–2 mg/kg/day orally. Liver function normalized in 3 weeks with resolution of ascites, oedema and pleural effusion. Scleroderma remained stable until day +145 after the second DLI, when it involved the arms, legs, thorax and abdomen. Diffuse joint contractures developed. Scleroderma with progression of joint contractures did not improve after an increase in CyA dose (3–5 mg/kg/day), addition of prednisone (1–2 mg/kg/day) and weekly i.v. methotrexate (10 mg/m2).

Table 1 Liver function, levels of IgG and anti-nuclear antibody, and scleroderma after second DLI
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  1. Bone Marrow Transplantation Unit, Department of Clinical and Morphological Research, Division of Haematology, University of Udine, Udine, Italy

    C Skert, F Patriarca, F Zaja, V Tomadini & R Fanin

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Skert, C., Patriarca, F., Zaja, F. et al. Acute hepatic failure as onset of progressive sclerodermatous chronic graft-versus-host disease after donor lymphocyte infusion. Bone Marrow Transplant 35, 523–524 (2005). https://doi.org/10.1038/sj.bmt.1704802

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