Summary:Bone marrow transplantation has been established as a useful treatment for various hematological disorders and is now performed widely, but the mortality rate is still high due to various complications. A clear therapeutic policy for such complications has not yet been established because of their complex nature. We investigated whether the major complications occurring after bone marrow transplantation could be classified as aspects of the systemic inflammatory response syndrome. Subjects were 10 patients who developed severe complications after bone marrow transplantation (graft-versus-host disease, thrombotic microangiopathy, respiratory disorders, and cytomegalovirus interstitial pneumonitis) and 16 patients without complications. Their symptoms, serum cytokines, and factors related to vascular endothelial damage were compared before and after transplantation. Whereas all 10 patients who developed complications had fever in the aplastic phase after transplantation, 15 of the 16 patients without complications remained afebrile (P Ͻ 0.001, t-test). When compared with the patients who did not develop complications, the patients with complications also showed significantly higher cytokine levels during the recovery phase after transplantation (P Ͻ 0.0001, t-test). Thus, the patients with complications developed fever in the aplastic phase and showed an increase of cytokines during the recovery phase, which triggered the occurrence of vascular endothelial damage shown by factors such as the thrombomodulin and plasminogen activator inhibitor type 1. This sequence of events corresponds with that occurring during systemic inflammatory response syndrome, so many of the complications of bone marrow transplantation can be considered as manifestations of this syndrome. Bone Marrow Transplantation (2000) 26, 419-426.

Summary:The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B 4 , thromboxane A 2 , and prostaglandin I 2 were significantly lower in patients receiving EPA than in those not receiving it (all P Ͻ 0.01). Cytokines such as tumor necrosis factor-␣, interferon-␥, and interleukin-10 were also significantly decreased by EPA (P Ͻ 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P Ͻ 0.05). The survival rate was significantly higher in the group given EPA (P Ͻ 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome. Bone Marrow Transplantation (2001) 28, 769-774.

Acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (BMT) is mediated by grafted T lymphocytes after their polarization into type 1 T cells. Interleukin (IL)-18, a novel immunoregulatory cytokine, strongly stimulates type 1 T cells, therefore we postulated that IL-18 may be involved in the pathogenesis of aGVHD. Using an enzyme-linked immunosorbent assay (ELISA), we serially measured serum levels of IL-18 in 37 patients with haematological malignancy before and after allogeneic BMT. Patients with aGVHD had high levels of IL-18 that strongly correlated with the severity of aGVHD. We also found that they showed reduced serum levels of IL-18 after appropriate treatment or at a state of resolution. IL-18 levels were not affected by the pretransplant regimen, engraftment or bacterial infection. Compared with circulating interferon (IFN)-gamma or IL-12 levels, serum levels of IL-18 showed a more sensitive and specific correlation with the disease status of aGVHD. These findings suggest that IL-18 may play important roles in the pathogenesis of aGVHD and that measurement of serum IL-18 levels can be useful indicator of aGVHD.

No abstract

Summary:Infection with cytomegalovirus (CMV) or human herpesvirus-6 (HHV-6) may have a role in vascular endothelial damage after bone marrow transplantation (BMT). In total, 41 patients who underwent BMT were classified into four groups (12, 10, 7, and 12 patients who were infected with both CMV and HHV-6, CMV alone, HHV-6, and neither virus, respectively). Levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were 7.571.7 FU/ml, 76.4724.1 ng/ml, and 9.5171.1 pmol/ ml, respectively, in the patients with both viruses, while the respective values were 2.970.67 FU/ml, 33.878.09 ng/ ml, and 2.9071.4 pmol/ml in patients infected with CMV alone, 4.870.96 FU/ml, 47.779.21 ng/ml, and 5.4870.55 pmol/ml in patients with HHV-6 alone, and 1.670.39, 17.577.88 ng/ml, and 0.4570.3 in those with neither virus. All three markers were significantly higher in the three groups with at least one virus than in the uninfected patients (Po0.05), and were also higher in patients with HHV-6 alone than in those with CMV alone (Po0.05). These results suggest that infection by CMV or HHV-6 causes vascular endothelial injury, with HHV-6 having a stronger effect than CMV, and combined infection having a stronger effect than either virus alone. Such viral infection may be a cause of thrombotic microangiopathy after BMT.