PMC9834550_01
Treatment course of hepatic veno-occlusive disease. Methylprednisolone was administrated at a dose of 1 mg/kg intravenously for 3 consecutive days and 1.5 mg/kg intravenously for 11 consecutive days. The effect was not and expected so that the dose of methylprednisolone gradually decreased to a maintenance dose of 12 mg per day. Tacrolimus was administrated at a dose of 0.5 mg twice daily. The dose was adjusted according to the trough concentration of tacrolimus. Azathioprine was used at a dose of 75 mg/m2 per day after 14 days of treatments of methylprednisolone. During the treatment, the level of total serum bilirubin further increased, and azathioprine was stopped after 12 days of treatment. Ruxolitinib at a dose of 5 mg per day and rituximab at a dose of 100 mg once a week were used for 2 weeks. However, the liver dysfunction and the symptoms of the patient aggravated during treatment. In order to exclude the possibility of drug toxicity, methylprednisolone, and tacrolimus were used as maintenance therapy and other drugs were stopped for 1 month. Unfortunately, the liver dysfunction of this patient continued to deteriorate. Therefore, methylprednisolone (1.5 mg/kg for 10 consecutive days and gradually decreased the dose to a maintenance dose of 12 mg), tacrolimus (0.5 mg twice daily, the dose was adjusted according to the trough concentration of tacrolimus), azathioprine (75 mg/m2 per day), rituximab (100 mg once a week), and ibrutinib (420 mg per day) were administrated. Mesenchymal stem cells (5.8 x 107/100 ml) were infused every 3 days for a total of three times. Plasma exchange (PE) was performed intermittently because of shortage of plasma. After HVOD was diagnosed, defibrotide was used at the dose of 6.25 mg/kg QID for 7 days. ALT, glutamic pyruvic transaminase; AST, glutamic oxaloacetic transaminase; BIL, bilirubin; TBIL, total serum bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin
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Consequently, deferasirox and treatments against cGVHD including methylprednisolone, tacrolimus, azathioprine, ruxolitinib, rituximab, ibrutinib, infusion of mesenchymal stem cells, and plasma exchange (PE) were performed (The details of treatment course are shown in Figure 1).
Magnetic resonance imaging scan (A,B). MRI sequence included T1WI, T2WI, and dynamic contrast-enhanced MR imaging. These patients presented heterogeneous signal of liver parenchyma in T1WI (Aa) and T2WI (Ab), hepatic vein and hepatic segmental interior vena cava narrowing (Aa,b), periportal edema (Ac) and ascites (Aa,c). After administration of the contrast agent (Ba,c), a diffuse heterogeneity in hepatic enhancement was observed. Early histology changes in hepatic sinusoidal obstruction syndrome (C). No infiltration of inflammation cells in the portal area of liver was found, and immunological injury of graft versus host reaction such as interlobular bile duct epitheliitis and vascular endothelitis was not observed, suggesting the exclusion of hepatic GVHD. The histology also showed partial dilatation and sinusoidal engorgement and extravasation of red blood cells through the space of Disse, associated with perivenular hepatocyte necrosis (at liver inflammation stages of G0, at liver fibrosis stages of S0) indicating pathological changes in the early stage of HVOD
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S1). She achieved complete remission (CR) after two chemotherapy courses with decitabine combined with CAG regimen (cytarabine 10 mg/m2 q12h, days 1-14; aclarubicin 14 mg/m2 qd, Days 1-4; granulocyte colony-stimulating factor 200ug/m2 qd, Days 1-14; (Figure S2). After administration of the contrast agent, during the portal phase, a diffuse heterogeneity in hepatic enhancement was observed (Figure 2A,B).