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Mahito Misawa

Publications and source records attributed to Mahito Misawa.

11 recordsLinked to original sources
PubMed2006

Heparin cofactor II as a predictor of thrombotic microangiopathy after bone marrow transplantation.

The pathogenesis of thrombotic microangiopathy (TMA) after allogeneic bone marrow transplantation (BMT) remains unclear since ADAMTS13, which is implicated in primary thrombotic thrombocytopenic purpura (TTP), has been shown to have no role in this condition. We investigated whether the onset of TMA after BMT could be predicted by measuring heparin-cofactor II (HC II), a marker for thrombosis of unknown etiology. In 30 consecutive BMT patients, the serum HC II level was measured before conditioning and one week after recovery from leukopenia. Four of the 30 patients developed TMA, and 26 did not. Before conditioning, the mean serum HC II level was 1.748 +/- 0.37 U/mL in the TMA group and 0.889 +/- 0.25 U/mL, in the non-TMA group, being higher in the former group (p < 0.01, t-test). After recovery from leukopenia, the two groups showed no significant difference of serum HC II. The HC II level at the onset of TMA was above the upper limit of normal in only one out of four patients. These results suggest that vascular endothelial damage due to chemotherapy before BMT increases the risk of TMA, and that HC II is useful for predicting the occurrence of TMA after BMT.

Adolescent↗
PubMed2006

Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow.

Reduced-intensity (RI) conditioning followed by cord blood transplantation (CBT) is a new treatment modality, but failure to engraft is a major concern. We describe 12 patients with advanced hematologic malignancies who underwent RI conditioning and CBT with a conditioning regimen consisting of 200 mg/m(2) fludarabine (Flu), 50 mg/kg cyclophosphamide (CY), and 3 Gy total body irradiation (TBI). Cyclosporin A and/or methotrexate were used for graft-versus-host disease prophylaxis. Cord blood grafts were not mismatched for more than 2 serologically defined HLA alleles but were later found by high-resolution DNA typing to be mismatched for 2 to 4 alleles in most cases. Short tandem repeat analysis of bone marrow cells at day 14 showed complete donor chimerism in 6 of the patients and mixed chimerism in 5, indicating rapid engraftment in the bone marrow, whereas the remaining patient experienced graft rejection. Neutrophil recovery was achieved at a median of day 17 (range, days 11-24) in 10 of the 11 patients with marrow chimerism at day 14. Of these 10 patients, however, transplantation-related mortality within 100 days occurred in 4 patients who showed failed platelet recovery and a lack of durable engraftment. Overall survival and disease-free survival rates were 41.7% and 33.3%, respectively. These results show that CB mismatched at 2 to 4 HLA alleles and transplanted with the Flu/CY/3 Gy TBI regimen is able to engraft in the bone marrow as early as day 14.

Adult↗
PubMed2005

Serum elastase and antithrombin-3 in patients with acute graft-vs.-host disease after bone marrow transplantation.

The mechanism by which inflammatory cytokines are involved in acute graft-vs.-host disease (GVHD) after hematopoietic stem cell transplantation has only been studied recently. We focused on the changes of serum elastase and antithrombin-3 (AT-3) from before pre-treatment until the leukocyte recovery period after transplantation. We examined the correlation between these two parameters and the grade of acute GVHD, as well as the mechanism of onset. We measured the serum elastase and AT-3 levels before pre-treatment and during the leukocyte recovery period in 49 consecutive patients receiving bone marrow transplantation. The severity of acute GVHD was divided into five grades (0-4). No significant differences of pre-transplantation elastase levels were observed among the GVHD grades, but the elastase level during the leukocyte recovery period showed a significant correlation with the grade of GVHD (p < 0.01). A significant inverse correlation was also observed (p < 0.05) between the pre-transplantation level of AT-3 and the grade of GVHD, as well as a significant correlation at the time of leukocyte recovery (p < 0.0001). Furthermore, a significant correlation (p < 0.0001) was observed between the elastase and AT-3 levels during the leukocyte recovery period. These results suggest that elastase levels during the leukocyte recovery period are related to the grade of acute GVHD and the mechanism appears to include vascular endothelial injury mediated via AT-3.

Acute Disease↗
PubMed2005

Heparin-induced thrombocytopenia antibody and the pathogenesis of thrombotic microangiopathy after stem cell transplantation.

Thrombotic microangiopathy (TMA) that occurs after stem cell transplantation (SCT) is generally regarded as being different from thrombotic thrombocytopenic purpura (TTP), because it is reportedly not associated with deficiency of von Willebrand factor-cleaving protease, whereas this enzyme is deficient in TTP. However, better understanding of the pathogenesis of this condition is still required. Accordingly, we investigated the relationship between TMA occurring after SCT and heparin-induced thrombocytopenia (HIT), a condition related to low-dosed heparin therapy that features thrombocytopenia and generalized thrombotic disorders. Thirty-nine consecutive patients who underwent bone marrow transplantation were divided into a TMA group and a non-microangiopathy group (10 and 29 patients, respectively). Before SCT, the serum platelet factor 4 (PF4) levels of the TMA and non-microangiopathy groups were 0.123 +/- 0.023 and 0.132 +/- 0.025, respectively (p = NS). One week after recovery of the white blood cell count following transplantation, the TMA group (0.2902 +/- 0.0678) had a significantly higher PF4 level than the non-microangiopathy group (0.1548 +/- 0.0312) (p < 0.001, t-test). Thus, PF4 increased after engraftment of the transplanted stem cells in the patients who developed TMA. In patients who developed TMA, there was a significant correlation between the PF4 level and the grade of angiopathy according to the Zeigler grading system (p < 0.01 by linear regression analysis). These results suggest that a HIT antibody produced by donor cells may be involved in the development of TMA after SCT.

Adolescent↗
PubMed2005

Relationships between hematological recovery and overall survival in older adults undergoing allogeneic bone marrow transplantation.

OBJECTIVE: The advancement of hematopoietic stem cell transplantation techniques and the increase in frequency of hematological malignancy in older patients are expected to expand the indications to include more elderly patients. We investigated the problem of allogeneic bone marrow transplantation (allo-BMT) in patients over 40 years old. PATIENTS AND METHODS: We retrospectively analyzed 21 consecutive patients (13 males and 8 females) over 40 years old who underwent allo-BMT at our center during the past 12 years. RESULTS: The patients had a median age of 46 years, and 5 patients were over 50 years old. There were 8 cases of acute myelogenous leukemia (AML), 5 cases of acute lymphocytic leukemia (ALL), 6 cases of chronic myelogenous leukemia (CML) and 2 cases of myelodysplastic syndrome (MDS). The 3-year overall survival rate was 43.0%. Overall survival was associated with recovery of platelets in less than 30 days and recovery of neutrophil counts in less than 15 days. We did not observe any severe graft-versus-host disease (GVHD) or regimen-related toxicities. Twelve patients died of transplantation-related diseases. CONCLUSION: A faster recovery of the neutrophil and platelet counts was significantly associated with overall survival. Decreasing transplantation-related death, particularly by infection control, in allo-BMT in patients over age 40 is an important problem.

Adult↗
PubMed2005

Usefulness of sequential automated analysis of fragmented red blood cells for the differential diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic hematopoietic cell transplantation.

Differentiating thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) from other complications following allogeneic hematopoietic cell transplantation (HPCT) requires objective, reliable markers. To this purpose, we assessed the clinical usefulness of sequential quantified analysis of fragmented red blood cells (FRC) with the Sysmex XE-2100 automated hematology analyzer. The correlation between manual and automated counting was significant (r = 0.917; P < .0001). Of 25 cases, the peak FRC percentage (FRC%) exceeded 1.3% after allogeneic HPCT in 11 cases, and lactate dehydrogenase levels were elevated in 5 of these 11 cases. Two patients received diagnoses of TTP-HUS following allogeneic HPCT, and both had initial diagnoses of acute graft-versus-host disease. In both cases, the sharp increase in the FRC% to >3% simultaneously with clinical exacerbation was helpful for differentiating TTP-HUS following allogeneic HPCT from other complications. We conclude that FRC% data sequentially obtained by an automated count seem to be useful as an objective marker of TTP-HUS following allogeneic HPCT.

Acute Disease↗
PubMed2004

Association of Helicobacter pylori with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation.

Thrombotic microangiopathy (TMA) has attracted attention as a complication of bone marrow transplantation (BMT). The association of Helicobacter pylori (H. pylori) with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS) after BMT was studied. Among 74 consecutive patients undergoing transplantation, six developed TTP/HUS (the TTP/HUS group) and 68 did not (controls). These six patients were compared with the other 68 patients to investigate differences of the IL-12 and 8 levels, H. pylori and various clinical characteristics. The patients who developed TTP/HUS seemed not apparently different from those who did not in background characteristics, except that they had a significantly higher H. pylori-positive rate (p < 0.05). In the TTP/HUS group, however, the levels of interleukin-12 and interleukin-8 increased significantly during the leukocyte recovery after BMT and at the onset of TTP/HUS, respectively, to 45.8 +/- 57.6 pg/mL and 274.8 +/- 65.9 pg/mL (p < 0.05 for both), when compared with their levels of 5.0 pg/mL in the control group. Thus, H. pylori may play a role in the pathogenesis of TTP/HUS after BMT, with cytokines (interleukin-8 and interleukin-12) also being involved.

Adolescent↗
PubMed2003

Analysis of natural killer (NK) cell activity and adhesion molecules on NK cells from umbilical cord blood.

The activity of natural killer (NK) cells in human umbilical cord blood (CB) has been reported to be low, compared with that in adult peripheral blood (PB) in vitro. To examine the cause of this, after dividing the CD56+/CD3- cells in CB and PB into CD56bright and CD56dim NK cells, the NK cell activities and the expression of various surface antigens were assayed for each fraction. The NK cell activity of CD56dim NK cells in CB was significantly lower than that in PB (P = 0.0003), whereas, there was no significant difference between the NK cell activity of CD56bright NK cells in PB and CB. The expression levels of adhesion molecules (CD2, CD11a, CD18, DNAX accessory molecule-1), CD16, and CD57 for CD56dim NK cells in CB were significantly lower than those in PB, and approximately one-third of CB CD56dim NK cells were capable of forming conjugates with K562 cells, compared with PB CD56dim NK cells. Furthermore, the inhibition of both the NK cell activities and binding of CD56dim NK cells in PB and CB by monoclonal antibody against each of these adhesion molecules suggests that they play an important role in NK cell activity. These findings show that the low NK cell activity in CB is caused by the low NK cell activity of CD56dim NK cells and that the low expression level of adhesion molecules on CB CD56dim NK cells may contribute to this low NK cell activity.

Antibodies, Monoclonal↗
PubMed2003

[New three-dimensional compensating filter for TBI using compu-former associated with RT LAN].

To shorten the TBI process, we developed a new device for making the three-dimensional (3D) compensating filter that improves dose distribution. The dose distributions in the phantom and manufacturing time were compared between the new device and the previous one. Clinical evaluations included dose distribution in patients and the clinical rate of interstitial pneumonitis (IP). Our 3D compensating filter is made of polystyrene resin and gypsum. The filter was made after performing two procedures as follows. Patient data were measured by CT, and the 3D dose-distribution data and 3D compensating-filter data were obtained from the CT data by the 3D radiation planning system. We were able to produce the new 3D compensating filter within about 4 hours, including all procedures. The average dose distribution to each site when the 3D compensating filter was used was 92.7% to the head, 102.1% to the thorax, 106.4% to the pelvis, 90.2% to the knee, and 93.8% to the ankle joint, when the scheduled dose was taken as 100%. Dose distribution was improved. IP occurred in 6 of 32 patients (18.8%). There was no significant difference between the TBI and non-TBI groups in the frequency of IP (p = 0.27).

Adolescent↗
PubMedDate not supplied

Changes of clotting factors (7, 9 and 10) and hepatocyte growth factor in patients with thrombotic microangiopathy after bone marrow transplantation.

To investigate risk factors for thrombotic microangiopathy (TMA) after bone marrow transplantation (BMT), the levels of three clotting factors (7, 9 and 10) and hepatocyte growth factor (HGF) were measured. Among 46 consecutive patients who underwent BMT, six developed TMA and 40 did not. The levels of the clotting factors and HGF did not differ significantly between the six patients with TMA and the 40 patients without it. In two patients who developed TMA during the earlyperiod after BMT, however, the levels of the three clotting factors were significantly decreased even before BMT, along with a significant increase of HGF. These findings suggest that patients with severe hepatic dysfunction before BMT, especially those with impaired protein synthesis, had an increased risk of developing TMA soon after BMT. It was also suggested that measurement of clotting factors (7, 9 and 10) and HGF may be useful to predict the occurrence of TMA in the early period after BMT.

Adult↗