Shigeki Kosugi

St. Marianna University School of Medicine, Kawasaki Si, Kanagawa, Japan

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Publications (8)13.19 Total impact

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    ABSTRACT: We report a rare case of non-Hodgkin lymphoma with mass lesions of skull vault and ileocecum. The patient was an 82-year-old Japanese woman who exhibited a painless subcutaneous scalp tumor in the right parietal region associated with no neurological abnormalities. Magnetic resonance imaging of the head demonstrated a mass in the skull vault with iso- to hypointense signals on both T1- and T2-weighted imaging. Biopsy of the mass revealed that the tumor comprised large cells that were immunoreactive for CD20 (L-26) and CD79a. Diffuse large B-cell lymphoma (DLBCL) was therefore diagnosed. Further investigation could not identify any other evidence of systemic lymphoma other than ileocecal lesions. She was treated by irradiation (45 Gy) of the mass on the parietal bone and with rituximab, pirarubicin, cyclophosphamide, and vincristine. The patient achieved complete remission after 3 cycles of systemic chemotherapy. As of 30 months after presentation, no signs of lymphoma have been found. [J Clin Exp Hematop 53(3) : 215-219, 2013].
    Journal of Clinical and Experimental Hematopathology 12/2013; 53(3):215-9. DOI:10.3960/jslrt.53.215
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    ABSTRACT: ABSTRACT High mobility group box 1 (HMGB1) mediates inflammation. We investigated the role of serum HMGB1 in 54 patients with hematological malignancies with and without systemic inflammatory response syndrome (SIRS). There was no difference between group1 (complete remission of hematological disease: n = 13) and 2 (no remission:n = 16) in serum HMGB1 levels. However, those of group 3 (complicated with SIRS: n = 25) were significantly higher (vs. group 1: p < 0.001 and vs. group 2: p=0.008, respectively). Seventeen patients in group 3 also developed DIC and received recombinant human thrombomodulin (rhTM). Thirteen of those with SIRS improved and serum HMGB1 levels significantly decreased (p = 0.047). Seven patients in group 3 who died within 28 days of SIRS onset had significantly higher serum HMGB1 levels than the survivors (p = 0.016). The anti-HMGB1 properties of rhTM might be useful therapy if serum HMGB1 is associated with the development of SIRS in the presence of hematological malignancies.
    Leukemia & lymphoma 01/2013; 54(9). DOI:10.3109/10428194.2012.752081 · 2.89 Impact Factor
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    ABSTRACT: Twice-daily administration of cyclosporine A (CyA) has often been used for prophylaxis of acute graft versus host disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT). But there have not been any reports that calculated the conversion ratio of the switch from twice-daily intravenous infusion to oral administration of CyA in adult patients. To establish the conversion ratio and the best strategy of twice-daily administration of CyA, the authors investigated the serial changes in the blood CyA concentration during the switch from twice-daily intravenous infusion to oral administration while maintaining high-peak concentration (over 1000 ng/mL) and calculated the bioavailability of Neoral, a micro emulsion cyclosporine, in 11 patients. All the patients underwent allo-HSCT with graft versus host disease prophylaxis consisting of CyA at a high-peak concentration of twice-daily infusion with short-term methotrexate and oral administration. Neoral was started at an oral dose, 2 times daily, at twice the latest dose of intravenous dose according to the bioavailability of healthy volunteers. Micafungin, a mild inhibitor of CYP3A4, was administered for prophylaxis against fungal infection. The total area under the concentration-time curve during oral administration (AUCpo) was nearly the same as AUC during intravenous infusion (AUCiv) (mean ± SD, 7206 ± 1557 ng·h·mL and 7783 ± 897.7 ng·h·mL, respectively). The bioavailability of Neoral, defined as F = AUCpo × DOSEiv/AUCiv × DOSEpo was 0.58 ± 0.15 (mean ± SD, range: 0.41-0.94). When patients were switched from twice-daily infusion to oral administration, the dose conversion ratio of 1:2 seemed to be appropriate. At that time, the target trough level of Neoral was nearly the same as that of the infusion.
    American journal of therapeutics 09/2012; 21(5). DOI:10.1097/MJT.0b013e318256ed25 · 1.13 Impact Factor
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    ABSTRACT: Objectives: The aim of this study was to assess the drug interaction between high doses of micafungin and cyclosporine A (CyA) in allo-HSCT patients. Methods: We assigned 15 patients to Groups 1, 2, or 3. We investigated the serial changes in the blood concentration/dose (C/dose) of intravenous CyA during micafungin coadministration in 5 patients during the switch from the prophylactic dose (150 mg/body) to the therapeutic dose (300 mg/body) of micafungin (Group 1), and compared each of the 5 patients in Group 1 with those who continued to receive the prophylactic doses of 150 mg or 50 mg/body of micafungin (Groups 2 and 3). We collected blood samples from patients in Group 1 receiving CyA at 0 h (C0) and (C3) 3 h on the 7th day after allo-HSCT, and on the 3rd and 10th days after escalation of the dose of micafungin to 300 mg. Results: In Group 1, no significant difference was observed between C0/dose (2.11 ± 0.14) and C3/dose ratios of CyA (11.1 ± 5.34, p > 0.05) under 150 mg; the C0/dose and C3/dose ratios of CyA were 2.40 ± 0.60 and 10.8 ± 4.72 on the 3rd day and 2.23 ± 0.41 and 11.8 ± 3.06 on the 10th day, respectively, after dose escalation of micafungin to 300 mg. No significant differences were observed in those ratios between Groups 1 and 2 and between Groups 1 and 3. Conclusion: Thus, high dose of micafungin seems to be safe and does not significantly interact with CyA in allo-HSCT.
    International journal of clinical pharmacology and therapeutics 09/2012; 50(11):831-7. DOI:10.5414/CP201738 · 1.22 Impact Factor
  • Thrombosis Research 06/2011; 127(6):603-4. DOI:10.1016/j.thromres.2010.12.023 · 2.45 Impact Factor
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    ABSTRACT: The most appropriate immunosuppressive strategy with calcineurin inhibitors for the prevention of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) has not yet been established. To estimate the safety and efficacy of a new strategy, we investigated the pharmacokinetics of cyclosporine A (CyA) delivered by twice-daily infusion and oral administration maintained with a peak level above 1000 ng/mL to keep 24 h area under the concentration-time curve (AUC0-24) higher than 10 000 ng·h/mL in 12 patients. Cyclosporine A was started as a twice-daily infusion at 1·5 mg/kg and then orally administered at twice the infusion dose to maintain the trough blood concentration between 200 and 500 ng/mL, and with a peak level above 1000 ng/mL. Serial blood samples were collected at 0, 1, 2, 3, 5, 8 and 12 h after CyA dosing (C0, C1, C2, C3, C5, C8 and C12) on days 14-21 after transplantation and on days 7-14 after switching to oral administration, and the AUC was calculated. In all patients, the AUC0-24 for both twice-daily infusion and oral administration was higher than 10 000 ng·h/mL. Two close relationships were observed between AUC0-12 and the C3 for infusion and between AUC0-12 and the C8 for oral administration. None of the patients had grades 3-4 aGVHD or other serious complications. This strategy was well tolerated, and the C3 for twice-daily infusion and the C8 for oral administration were the optimal points for monitoring of CyA concentration in the early phase of transplantation.
    Journal of Clinical Pharmacy and Therapeutics 11/2010; 36(4):518-24. DOI:10.1111/j.1365-2710.2010.01199.x · 1.67 Impact Factor
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    ABSTRACT: A 43-year-old Japanese woman underwent unrelated cord blood transplantation (CBT) during remission for acute lymphoblastic leukemia with t(4; 11)(q21;q23). Tacrolimus was given for prophylaxis of graft-versus-host disease. The posttransplantation clinical course was mostly uneventful, and the leukemia remained in remission. Fourteen months after CBT, the patient developed pancytopenia and hepatic dysfunction with persistent high-grade fever. The bone marrow was hypocellular with increased numbers of macrophages and hemophagocytes. The numbers of Epstein-Barr virus (EBV) copies in peripheral blood samples were remarkably high. Although the patient showed complete donor-type hematopoiesis, the titer of viral capsid antigen immunoglobulin G was low, and the results of a test for EBV nuclear antigen were negative. There was no clinical response to the reduction of immunosuppressive therapy or to the administration of high-dose methylprednisolone, human immunoglobulin, or acyclovir. The patient died 466 days after CBT of massive gastrointestinal hemorrhage due to bone marrow and hepatic failures. This case demonstrates that fatal EBV-associated hemophagocytic syndrome (HPS) can occur more than 1 year after CBT. This report is the first of a case of late-onset EBV-associated HPS following CBT.
    International Journal of Hematology 01/2007; 84(5):445-8. DOI:10.1532/IJH97.06101 · 1.92 Impact Factor
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    ABSTRACT: A 60-year-old Japanese man with myelodysplastic syndrome (MDS) and effort angina was referred to our clinic for treatment of MDS. The patient was transfusion-dependent and displayed coronary artery disease (CAD) with 99% obstruction of the left anterior descending coronary artery. Treatment comprised reduced-intensity hematopoietic stem cell transplantation with administration of fludarabine phosphate (180 mg/m(2)) and busulfan (8 mg/kg), followed by allogeneic peripheral blood stem cell transplantation from an HLA-matched sister. The regimen was well tolerated, and engraftment occurred rapidly without any therapy-related complications, including cardiovascular attack. Sex chromosome analysis by fluorescence in situ hybridization revealed complete donor chimerism on day 29 for bone marrow cells and on day 59 for peripheral blood leukocytes. The patient became transfusion-independent on posttransplantation day 8. As of 22 months postoperatively, he remains well, with 100% Karnofsky performance status, a limited type of chronic graft-versus-host disease, and no recurrence of disease. The clinical course of the patient suggests that this preparative regimen allows safe allogeneic stem cell transplantation for MDS patients with severe CAD.
    International Journal of Hematology 03/2006; 83(2):156-8. DOI:10.1532/IJH97.05057 · 1.92 Impact Factor