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ABSTRACT: Cutaneous GVHD is histologically similar to eruptions induced by drugs containing a sulfhydryl group. The levels of interleukin-2 and interleukin-2 receptor were determined in a group of patients undergoing bone marrow transplantation (BMT) without graft-versus-host disease or any other complications and in a group with cutaneous graft-versus-host disease (GVHD) alone. In patients who only developed cutaneous GVHD, both interleukin-2 and inter-leukin-2 receptor levels were elevated when the disease was evident. As the elevation of these parameters became more marked, the grade of cutaneous graft versus-host disease also increased. In some patients, only one of the two parameters was elevated and the grade of graft-versus-host disease was low or no skin manifestations were seen. These findings suggest that interleukin-2 and interleukin-2 receptor act together in the development of cutaneous GVHD. This study also showed that the mechanism of cutaneous GVHD resembles that involved in the induction of eruptions by sulfhydryl-containing drugs.
Hematology 03/2002; 7(1):55-7. · 1.49 Impact Factor
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ABSTRACT: We investigated whether pretreatment with eicosapentaenoic acid, an inhibitor of leukotriene (LT) B4, could ameliorate acute colonic graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). Seventeen patients undergoing unrelated BMT were divided into two groups, with eight patients receiving eicosapentaenoic acid and nine not receiving it. The grade of GVHD after transplantation was compared with that estimated from the pretransplantation LTB4 level. The levels of LTB4 and several cytokines were also monitored. The actual grade of GVHD was lower than that estimated from LTB4 levels in three of the eight patients from the treated group, and there was a significant difference between the treated and untreated groups (p < 0.05, chi 2 test). The levels of LTB4, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were all significantly lower in the treated group (p < 0.05, Student's t-test). These findings suggest that eicosapentaenoic acid may ameliorate acute colonic GVHD when administered from before BMT.
Drugs under experimental and clinical research 01/2002; 28(4):121-5.
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ABSTRACT: Urinary trypsin inhibitor has attracted attention as an index of the systemic inflammatory response syndrome. In this study, the urine concentration of trypsin inhibitor was measured to compare the immunological insult of conventional chemotherapy and conditioning chemotherapy for bone marrow transplantation. We also investigated whether urinary trypsin inhibitor was a useful index of the complications and outcome of bone marrow transplantation. Urinary trypsin inhibitor concentration was determined before chemotherapy, on the day after finishing chemotherapy (day 0 of transplantation), and during recovery of the white cell count, in 17 patients (seven receiving conventional chemotherapy and 10 receiving conditioning for bone marrow transplantation). Urinary trypsin inhibitor concentrations were significantly higher after conditioning for bone marrow transplantation than after conventional chemotherapy (P < 0.001), indicating that conditioning was more invasive. After bone marrow transplantation, the incidence of severe complications and the mortality rate were higher in patients whose urinary trypsin inhibitor concentrations rose during recovery of the white cell count. Comparison of urinary trypsin inhibitor concentrations suggested that conditioning for bone marrow transplantation was more invasive than conventional chemotherapy. This study also suggested that the urine concentration of trypsin inhibitor could be useful for predicting the risk of complications and outcome of bone marrow transplantation.
Bone Marrow Transplantation 01/2001; 27(2):195-9. · 3.75 Impact Factor
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ABSTRACT: Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.
Bone Marrow Transplantation 01/2001; 26(12):1313-6. · 3.75 Impact Factor
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ABSTRACT: 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 < 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 < 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 08/2000; 26(4):419-26. · 3.75 Impact Factor
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ABSTRACT: Certain human leukocyte antigens may increase the risk of cytomegalovirus interstitial pneumonitis, an important complication of bone marrow transplantation. The prevalence of this pneumonitis was compared between patients possessing either HLA-B51 or HLA-B52 and patients without either antigen. The role of tumor necrosis factor-alpha in cytomegalovirus interstitial pneumonitis was also studied. Among 72 patients undergoing allogeneic bone marrow transplantation at our institution during the past 5 years, HLA-B51 or -B52 was detected in 29. Among these 29 patients, 13 (45%) developed cytomegalovirus interstitial pneumonitis, a significantly higher rate (P < 0.001) than among patients without these HLA types (4/43, 9%). In the pre-conditioning and stable phases, tumor necrosis factor-alpha levels were higher in patients with HLA-B51 or HLA-B52 than in patients without (P < 0.05; t-test). Throughout the period from pre-conditioning to around day 40, except on day 0, tumor necrosis factor-alpha levels were also significantly higher (P < 0.05 to P < 0.001) in patients developing cytomegalovirus infection than in those without it. These results suggest that HLA-B51 and HLA-B52 may be risk factors for cytomegalovirus interstitial pneumonitis after bone marrow transplantation, with an increase of tumor necrosis factor-alpha also being involved.
Bone Marrow Transplantation 04/2000; 25(8):861-5. · 3.75 Impact Factor
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T Okamoto,
Y Nishimura, S Yamada,
T Itoh,
A Mori,
K Saheki,
M Okada,
H Takatsuka,
H Wada,
A Tamura,
Y Fujimori,
E Kakishita
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ABSTRACT: It is known that the topoisomerase II inhibitors, MST-16 (sobuzoxane) and VP-16 (etoposide), are effective for the treatment of lymphoma. Five patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) were treated with a combination of oral MST-16 and VP-16 over a long period. Two patients had severely refractory NHL. The remaining 3 patients could not be treated with intensive chemotherapy because of severe organ dysfunction or a poor hematopoietic reserve. All 5 are alive and well after MST-16 and VP-16 treatment. MST-16 and VP-16 are effective for NHL when intensive chemotherapy is ineffective or contraindicated.
Acta Haematologica 02/2000; 104(2-3):128-30. · 1.35 Impact Factor
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H Takatsuka,
T Okamoto, S Yamada,
Y Fujimori,
S Tamura,
H Wada,
M Okada,
Y Takemoto,
H Nishimura,
H Tachibana,
A Kanamaru,
E Kakishita
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ABSTRACT: Central nervous system disorders are an important complication of bone marrow transplantation (BMT). We have recently performed cerebral angiography to examine central nervous system dysfunction in a 22-year-old woman with acute lymphoblastic leukaemia who had undergone BMT. Angiography demonstrated multiple stenoses and occlusions in the peripheral branches of the anterior and middle cerebral arteries, a pattern similar to that seen in vasculitis. She was thought to most likely have cytomegalovirus (CMV) vasculitis, but other forms of vasculitis, such as angiitis-like-syndrome-associated graft-versus-host disease could not be excluded. This case suggests that CMV vasculitis may cause central nervous system dysfunction after BMT and that imaging studies may provide useful information about central nervous system disorders in these patients.
Acta Haematologica 02/2000; 103(4):203-5. · 1.35 Impact Factor
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Y Fujimori,
K Saheki, S Yamada,
A Mori,
T Itoh,
M Okada,
H Takatsuka,
H Wada,
S Tamura,
T Okamoto,
Y Takemoto,
E Kakishita,
K Nagai
International Journal of Hematology 11/1999; 70(3):207-8. · 1.27 Impact Factor
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ABSTRACT: Acute graft-versus-host disease (GVHD) is the most important complication of allogeneic bone marrow transplantation. We investigated the possibility of predicting severe acute GVHD using plasma interleukin-10 levels in 31 patients who underwent allogeneic bone marrow transplantation. In patients with acute GVHD, the interleukin-10 (IL-10) level increased significantly from the aplastic phase through the leukocyte recovery phase after transplantation (P < 0.05, paired t-test). The ratio of the IL-10 level in the aplastic phase to that in the leukocyte recovery phase was significantly correlated with the severity of acute GVHD (P < 0. 05, t-test), and the incidence of grade III or IV disease was significantly increased (P < 0.0001). Since IL-10 antagonizes various other cytokines that induce acute GVHD, determination of the IL-10 level is equivalent to assessing the total production of cytokines promoting GVHD. The ratio of the IL-10 level in the aplastic phase to that in the recovery phase seems to be useful for predicting the subsequent risk of acute GVHD.
Bone Marrow Transplantation 11/1999; 24(9):1005-7. · 3.75 Impact Factor
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M Okada,
T Okamoto, S Yamada,
T Itoh,
A Mori,
K Saheki,
H Takatsuka,
H Wada,
Y Tamura A,
Y Fujimori,
Y Takemoto,
E Kakishita
Acta Haematologica 02/1999; 102(2):107-9. · 1.35 Impact Factor
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ABSTRACT: The expression of leukocyte alkaline phosphatase (LAP) in neutrophils is reduced in some patients with myelodysplastic syndrome (MDS). We quantitatively assayed for LAP in MDS leukocytes by a flow cytometry based method using a monoclonal antibody raised against human bone alkaline phosphatase. The LAP expression was assayed in blood samples from a group of 46 MDS patients, consisting of 39 patients with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 4 patients with RAEB in transformation. The percentage of LAP-positive cells was significantly higher in the MDS patients than in the normal subjects and also higher in RA than in RAEB and RAEB in transformation. To investigate the cause of the elevated LAP expression, we measured the serum concentrations of several cytokines. The granulocyte colony-stimulating factor (G-CSF) level was significantly elevated in MDS patients, and the serum G-CSF concentration clearly correlated with the percentage of LAP-positive cells. Thus, the LAP activity in RA is higher than in normal subjects, and G-CSF is thought to be one of the causes stimulating LAP expression in MDS neutrophils.
Acta Haematologica 02/1999; 102(2):89-93. · 1.35 Impact Factor
