Clinical Implications Of Severe Isolated Hepatic Gvhd Post-DLI

Donor lymphocyte transfusion (DLI) may induce the graft-versus-leukemia (GVL) effect, but may also increase the risk of graft-versus-host disease (GVHD). Thus, the escalating-dose DLI and/or co-administration with short-term immunosuppressive agents are one of the clinical strategies to keep the balance between GVHD / GVL nowadays.

Here we review the clinical manifestation of GVHD post–DLI, and discuss its clinical implication.

In this retrospective study, 15 consecutive patients in high risk underwent 41 times DLI after the transplantation for acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, myelodysplastic syndrome and lymphoma since 2009 are studied. The median age of patients was 33 years (range 8 to 51 years). All patients have an HLA-identical sibling donor and achieved full donor chimerism soon after the myelosuppressive conditioning. DLI were used regularly in escalating-dose and co-administration with short-term immunosuppressive agents (low dose cyclosporine A and methylprednisolone). Except 1 case received DLI in combination with low-dose cytarabine for the treatment of relapsed AML, all the other cases were given pre-emptive DLI 4 months after the transplantation. All cases initially have no clinical signs of liver damage, acute and/or chronic GVHD, and severe infection. After viral hepatitis and recent drug exposure are excluded, the possible relationship between correlation between the liver dysfunction and the clinical features of GVHD are evaluated.

8 out of 15 cases developed GVHD post-DLI, of whom 3 had isolated liver involvement after the first infusion, and 5 had a limited skin rash and liver involvement after the second or third infusion. Liver function tests showed the elevated aminotransferases with hyperbilirubinemia in 3 cases with isolated liver involvement, but without hyperbilirubinemia in the other 5 cases. Serum gamma-glutamyltransferas(GGT) was persistently elevated in all these 8 cases, and the peak levels of which in all 3 cases with isolated liver involvement were 30-50 times of the normal upper limit, while a slight elevation in the other 5 cases. After the viral hepatitis and recent drug exposure were excluded, liver biopsy was then performed and revealed lymphocytic infiltration of the portal tracts and vacuolization of the biliary epithelial cells. There were also pictures of the loss of bile ducts and increased fibrosis, which was compatible with the diagnosis of GVHD of cholangiohepatitic type. 3 cases with severe hepatic GVHD were finally died of the progression of GVHD in 7 months (1 case) or disease relapse (2 cases) in 1-2 years. All the other 5 cases are still alive with the disease-free survival of 38 months.

The findings indicate that isolated hepatic GVHD might be a distinct clinical feature in DLI, which is different to the classic GVHD post transplantation. Persistent Elevation of GGT might serve as a marker of hepatic GvHD post-DLI. Furthermore, how to balance of GVHD and GVL is very complex, while the prevention of GVHD would be associated with the loss of immune reconstitution and GVL.

No relevant conflicts of interest to declare.