Child ; Female ; Hepatic Veno-Occlusive Disease ; diagnosis ; pathology ; therapy ; Humans ; Liver ; pathology

Adult ; Hepatic Veno-Occlusive Disease ; diagnosis ; therapy ; Humans ; Male ; Middle Aged

China ; Consensus ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatic Veno-Occlusive Disease/therapy* ; Humans ; Transplantation Conditioning

OBJECTIVETo improve the treatment of drug related childhood hepatic veno-occlusive disease (HVOD), clinical characteristics of 6 children with hematologic neoplasm from 2 hospitals of China Children's Leukemia Group (CCLG) treated with 6-thioguanine (6-TG) complicated with HVOD were analyzed.

METHODAll the drug related HVOD patients were treated with CCLG acute lymphoblastic leukemia (ALL)-2008 protocol. They were from Children's Hospital of Fudan University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from April 2008 to April 2009. The diagnosis was made according to the modified Seattle criteria and Baltimore criteria, including 2 or 3 of the following clinical features: hepatomegaly and upper right abdominal pain, jaundice (bilirubin ≥ 35 µmol/L), ascites or confirmed by pathology. The 6 HVOD patients' clinical manifestations, laboratory finding, imageologic and pathologic data were collected and analyzed.

RESULTOf the 6 patients, 2 were males and 4 females. Mean age of the 6 patients was 3.89 years (range from 3 years 1 month to 4 years 11 months). The original disease was acute lymphoblastic leukemia. HVOD occurred during chemotherapy protocols of CAM (CTX + Ara-C + 6-TG) or maintenance period (MTX + 6-TG). Most of 6 HVOD patients presented with pain in liver area, hepatomegaly on imaging, elevated aminotransferase and bilirubin (often ≥ 35 µmol/L), hydroperitonia was common, one with pleural fluid, illegible hepatic veins. All the patients recovered after being treated with hepatoprotective, jaundice-relieving and supportive therapeutics, some patients were treated with low molecular weight heparin. The prognoses were good.

CONCLUSIONHVOD was a serious complication of chemotherapy with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight heparin could improve the prognosis.

Antineoplastic Agents ; therapeutic use ; Child, Preschool ; Female ; Hepatic Veno-Occlusive Disease ; drug therapy ; Humans ; Leukemia ; therapy ; Male ; Thioguanine ; therapeutic use

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.
Child* ; Cyclophosphamide* ; Drug Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Hepatic Veno-Occlusive Disease* ; Humans ; Liver ; Rhabdomyosarcoma* ; Vincristine*

OBJECTIVETo summarize the clinical experiences in the diagnosis and managements of hepatic veno-occlusive disease (HVOD).

METHODSThe clinical and pathologic data of 17 patients with hepatic veno-occlusive disease were analyzed retrospectively.

RESULTSAccording to the results of imaging examination, clinical data and pathological data, 17 patients HVOD were divided into acute progressive HVOD and chronic HVOD. 2 cases out of the 11 acute progressive cases got improved, 2 cases died after medical treatment and 2 cases died after shunt operation. The 6 chronic HVOD, including 1 case with medical treatment and 5 cases with shunt operation, were cured.

CONCLUSIONLiver biopsy was an efficient method for the diagnosis of hepatic veno-occlusive disease. Acute progressive cases of hepatic veno-occlusive disease should be managed with medical treatment and the chronic cases could be treated with shunt surgery if medical treatment were inefficient.

Adult ; Aged ; Female ; Hepatic Veins ; pathology ; Hepatic Veno-Occlusive Disease ; diagnosis ; pathology ; therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.
Colorectal Neoplasms* ; Disease-Free Survival ; DNA ; Drug Therapy ; Fluorouracil ; Hepatic Veno-Occlusive Disease ; Humans ; Leucovorin ; Platelet Count ; Polymorphism, Genetic* ; Spleen ; Splenomegaly* ; Thrombocytopenia ; Treatment Outcome*

OBJECTIVETo summarize the clinical features of sinusoidal obstruction syndrome (SOS) and to improve the understanding of this disease.

METHODSA retrospective study was performed on the clinical data of 12 children with SOS including clinical manifestations, laboratory results, imaging findings, treatment, and prognosis.

RESULTSOf the 12 cases, 8 were secondary to acute lymphoblastic leukemia, and 4 had undergone hematopoietic stem cell transplantation. Manifestations mainly included abdominal distention (4 cases), hepatomegaly with tenderness (9 cases), splenomegaly (6 cases), and weight increase (10 cases). Biochemical tests revealed varying degrees of liver damage in all cases. In the coagulation function test, the activated partial thromboplastin time (APTT) was prolonged in 7 cases. Out of the 7 patients who underwent serum D-dimer test, 4 showed elevated serum level of D-dimer. In routine blood tests, 4 cases showed decreases in both white blood cells and neutrophils. In addition, varying degrees of thrombocytopenia were observed in 9 cases. Eight patients were subjected to color Doppler ultrasound examination, and diffuse hepatomegaly, inhomogeneous liver parenchyma, unclear or thinner hepatic veins, hydrothorax/ascites, or splenomegaly was observed. Sinusoidal dilatation or hepatic cell infiltration was observed in 2 patients who underwent liver biopsy. Treatments were basically symptomatic and supportive therapies, and the prognosis was good in all patients.

CONCLUSIONSSOS should be considered in children who present with hepatomegaly, sudden weight gain, liver dysfunction and coagulation dysfunction after they have received chemotherapy for leukemia and hematopoietic stem cell transplantation.

Child ; Child, Preschool ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Hepatic Veno-Occlusive Disease ; blood ; therapy ; Humans ; Male ; Retrospective Studies ; Tomography, X-Ray Computed

BACKGROUND: The unpredictable intestinal absorption and bioavailability of oral busulfan (BU) has limited the drug's use in high-dose pretransplant conditioning therapy. To overcome these problems, several trials for the evaluation of pharmacokinetics and clinical usefulness of an intravenous BU (IVBU) formulation have been reported. Here we present clinical and pharmacokinetic data on patients receiving IVBU as a component of conditioning regimens for allogeneic stem cell transplantation (SCT) in our center. METHODS: A total of 6 adult patients were entered onto this study. All patients were treated with IVBU (0.8mg/kg every 6 hours x 8~16)-containing conditioning regimen followed by HLA-identical allogeneic SCT. We also investigated the pharmacokinetics of IVBU using high-performance liquid chromatography in two cases. RESULTS: All patients achieved successful engraftment. No patient experienced hepatic veno-occlusive disease or neurologic toxicity. Five of 6 patients still alive in complete remission have been followed for 8~12 months after SCT. The measured maximum concentration for the first dose was 1,175ng/mL and 951ng/mL, and the half-life was 2.25h and 3.09h, respectively. The area under the plasma concentration-time curve was 4,596ng h/ mL and 3,067ng h/mL, respectively. There was no significant difference between the first and last dose pharmacokinetic parameters. CONCLUSION: We suggest that IVBU should be considered as appropriate replacement for oral BU in pretransplant conditioning therapy prior to SCT in Korea. Further studies with sizable patients are needed to define the role of IVBU in SCT setting.
Adult ; Behavior Therapy ; Biological Availability ; Busulfan* ; Chromatography, Liquid ; Half-Life ; Hepatic Veno-Occlusive Disease ; Humans ; Intestinal Absorption ; Korea ; Pharmacokinetics* ; Plasma ; Stem Cell Transplantation* ; Stem Cells*

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.
Animals ; Bile ; Bile Acids and Salts ; Endothelial Cells/metabolism* ; Hepatic Veno-Occlusive Disease/pathology* ; Inflammation/pathology* ; Liver Cirrhosis/drug therapy* ; Mice ; Powders ; Pyrrolizidine Alkaloids/adverse effects* ; Ursidae