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.

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SummaryBernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder, which is caused by deficiency or decrease of the platelet GPIb/IX/V complex. Analysis of two patients with BSS by How cytometry of the blood revealed different expression patterns of the components of the GPIb/IX/V complex. In case 1, GPIX was completely absent but residual amounts of GPIbα and GPV were detectable; in case 2, GPIbα was completely absent. We amplified the coding regions of GPIbα, GPIbß, GPV, and GPIX from the patients’ genomic DNA with the polymerase chain reaction (PCR) and sequenced the PCR products. In case 1, we identified a point mutation in the GPIX coding region that changes the codon for tryptophan-126 (TGG) to a nonsense codon (TGA). In case 2, we found a deletion of nucleotide within seven adenine repeats at the position of 1932 to 1938 in the coding region of GPIbα, which causes a frame shift that results in 58 altered amino acids and a premature stop codon. These genetic changes alter the transmembrane domain of GPIX or GPIbα and, therefore, would prevent proper insertion of the proteins in the plasma membrane. Thus, abnormality of a single component protein (GPIX or GPIbα) alters the assembly of the GPIb/IX/V complex and causes heterogenous surface expression of GPIbα, GPV and GPIX.

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