Yoshinobu Maeda

Okayama University, Okayama, Okayama, Japan

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Publications (84)369.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-Mannan, a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. α-Mannan induced donor T cell polarization towards Th17 and lung specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of α-Mannan on GVHD depended on donor IL-17A production and host c-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection following allogeneic HSCT. Copyright © 2015 American Society of Hematology.
    Blood 03/2015; DOI:10.1182/blood-2014-12-615781 · 9.78 Impact Factor
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    ABSTRACT: Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation. Recently, in addition to Th2 cells, Th1 and Th17 cells have been shown to contribute to chronic GVHD progression. IL-12 induces Th1 cells and IL-23 plays a role in stabilizing and/or amplifying Th17 cells, as well as in inducing IFN-γ/IL-17 double-producing cells. Because mAb targeting the p40 subunit common to both IL-12 and IL-23 can inhibit both IL-12R and IL-23R-mediated signaling, we investigated the effects of anti-p40 mAb on a well-defined chronic GVHD mice model. Treatment of anti-p40 mAb in allogeneic recipients significantly reduced the severity of clinical and pathological chronic GVHD. Intracellular staining revealed that IFN-γ single-positive (IL-17(-)) and IFN-γ/IL-17 double-positive cells were suppressed in anti-p40 mAb-treated allogeneic recipients compared with control recipients. The cytokine levels of IFN-γ and IL-17 were also decreased in serum from anti-p40 mAb-treated allogeneic recipients. T-bet expression of donor IL-17(+) CD4(+) T cells was reduced significantly in anti-p40 mAb-treated recipients, and this reduction in T-bet expression was associated with IL-22 production by donor T cells. These results suggested that anti-p40 mAb attenuated chronic GVHD via suppression of IFN-γ/IL-17-producing cells, and that targeting the IL-12/IL-23 pathway may represent a promising therapeutic strategy for preventing and treating chronic GVHD. Copyright © 2014 by The American Association of Immunologists, Inc.
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    ABSTRACT: Although high-dose methotrexate and whole-brain radiation therapy (WBRT) is the current standard for primary central nervous system lymphoma (PCNSL), it has a limited response rate and produces radiation-induced neurotoxicity. We report the effect of a combined treatment of high-dose methotrexate, cyclophosphamide, doxorubicin, vincristine and prednisolone (M-CHOP) for immunocompetent patients with PCNSL.Methods We analyzed 24 patients who had received M-CHOP administered in 28-day cycles with or without WBRT. The response rate to M-CHOP, overall survival (OS), and recurrence-free survival (RFS) were analyzed.ResultsNine patients were treated with M-CHOP plus WBRT and 15 patients were treated with M-CHOP alone. Twenty-one patients achieved a complete response and three patients achieved a partial response to M-CHOP, for a 100% response rate. With a median follow-up of 70 months, the median OS and RFS were 33 and 13 months, respectively. The median OS for patients treated with M-CHOP plus WBRT and M-CHOP alone was 33 and 32 months, respectively. Of the 13 patients whose age was above 65 years, the median OS for the M-CHOP plus WBRT group (two patients) and the M-CHOP alone group (11 patients) was 14 and 32 months, respectively. Toxicities related to M-CHOP were mostly hematologic and generally mild to moderate. Two patients whose age was above 65 years in the M-CHOP plus WBRT group developed neurotoxicity.Conclusion Combined treatment with M-CHOP was well tolerated and produced a high response rate. Deferring WBRT was associated with reduced neurotoxicity without worsening the prognosis, especially in elderly patients.
    Clinical Neurology and Neurosurgery 10/2014; 127. DOI:10.1016/j.clineuro.2014.10.011 · 1.25 Impact Factor
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    ABSTRACT: The prognosis of patients with primary mediastinal large B-cell lymphoma has improved during recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow-up of 48 months, the overall survival at 4 years for patients treated with R-CHOP (N = 187), CHOP (N = 44), DA-EPOCH-R (N = 9), second- or third-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher IPI and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy [IPI: hazard ratio, 4.23; 95% confidence interval, 1.48-12.13; P = 0.007; effusion: hazard ratio , 4.93; 95% confidence interval , 1.37-17.69; P = 0.015]. Combined with IPI and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower IPI and the absence of the effusion comprised approximately one-half of these patients and could be identified as curable patients [overall survival at 4 years, 95%]. The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of IPI and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment.
    Haematologica 09/2014; 99(12). DOI:10.3324/haematol.2014.111203 · 5.87 Impact Factor
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    ABSTRACT: Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the role of the programmed death-1 (PD-1) pathway in chronic GVHD using a well-defined mouse model of B10.D2 (H-2(d)) donor to BALB/c (H-2(d)) recipients. PD-1 expression on allogeneic donor T cells was upregulated continuously in chronic GVHD development, whereas PD-L1 expression in host tissues was transiently upregulated and declined to basal levels in the late posttransplant period. Blockade of the PD-1 pathway by anti-PD-1, anti-PD-L1, or anti-PD-L2 mAbs exacerbated clinical and pathologic chronic GVHD. Chimeric mice revealed that PD-L1 expression in host tissues suppressed expansion of IL-17(+)IFN-γ(+) T cells, and that PD-L1 expression on hematopoietic cells plays a role in the development of regulatory T cells only during the early transplantation period but does not affect the severity of chronic GVHD. Administration of the synthetic retinoid Am80 overcame the IL-17(+)IFN-γ(+) T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1(-/-) recipients. Stimulation of the PD-1 pathway also alleviated chronic GVHD. These results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronic GVHD.
    The Journal of Immunology 07/2014; 193(5). DOI:10.4049/jimmunol.1400954 · 5.36 Impact Factor
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    ABSTRACT: Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42–89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus IgH/BCL-2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) (MYD88) L265P mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; immunoglobulin M and G paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and MYD88 L265P mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.
    Human pathology 07/2014; 45(7). DOI:10.1016/j.humpath.2014.02.010 · 2.81 Impact Factor
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    ABSTRACT: Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an aggressive lymphoma consisting of clonal proliferation of mature activated γδ T-cells of a cytotoxic phenotype. Because PCGD-TCL is a rare disease, there are few clinicopathological study reports. In addition, T-cell receptor (TCR) γδ cells are typically immunostained in frozen sections or determined by TCRβ negativity. We retrospectively analyzed 17 primary cutaneous T-cell lymphomas of the γδ phenotype (CTCL-γδ) in a clinicopathological and molecular study using paraffin-embedded sections. Eleven of 17 patients had CTCL-γδ without subcutaneous panniculitis-like T-cell lymphoma (SPTCL) features and 6 had CTCL-γδ with SPTCL features. Immunophenotypically, some significant differences were found in CD8 and CD56 positivity between our patient series of CTCL-γδ patients with SPTCL features and SPTCL-γδ patients described in the previous literature. The univariate analysis of 17 CTCL-γδ patients showed that more than 60 years old age, presence of visceral organ involvement, and small-to-medium cell size were poor prognostic factors. In addition, the 5-year overall survival rate was 42.4% for the CTCL-γδ patients without SPTCL features and 80.0% for those with SPTCL features. Consequently, there was a strikingly significant difference in overall survival among SPTCL, CTCL-γδ with SPTCL features and CTCL-γδ without SPTCL features (P = 0.0005). Our data suggests that indolent subgroup may exist in CTCL-γδ. Studies on more cases including multinational areas are warranted to delineate the clinicopathological features and the significance in these rare lymphomas.This article is protected by copyright. All rights reserved.
    Cancer Science 05/2014; DOI:10.1111/cas.12439 · 3.53 Impact Factor
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    ABSTRACT: Several high-risk HLA-allele mismatch combinations (HR-MMs) for severe acute GVHD have been identified by analyzing transplant outcomes in Japanese unrelated hematopoietic stem cell transplantation recipients. In this study, we reanalyzed the effects of HR-MMs in three transplantation time periods. We confirmed that the incidence of grade III-IV acute GVHD in the HR-MM group was significantly higher than that in the low-risk (LR) MM group (hazard ratio [HR] 2.74, p<0.0001) in the early time period (1993-2001). However, the difference in the incidence of grade III-IV acute GVHD between the HR-MM and LR-MM groups was not statistically significant (HR 1.06, p=0.85 and HR 0.40, p=0.21, respectively) in the mid (2002-2007) and late (2008-2011) time periods. Similarly, survival in the HR-MM group was significantly inferior to that in the LR-MM group (HR 1.46, p=0.019) in the early time period, whereas the difference in survival between the two groups was not statistically significant in the mid and late time periods (HR 1.06, p=0.75 and HR 0.82, p=0.58, respectively). In conclusion, the adverse impact of HR-MM has become less significant over time periods. Unrelated transplantation with a single HR-MM could be a viable option in the absence of a matched unrelated donor or an unrelated donor with a single LR-MM.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2014; DOI:10.1016/j.bbmt.2014.01.003 · 3.35 Impact Factor
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    ABSTRACT: Bronchiolitis obliterans (BO) is a devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively studied 465 patients who underwent HSCT in the Okayama BMT Group between 2000 and 2009, and describe the detailed clinical features of 13 patients with BO. The 5-year cumulative incidence of BO was 3.43 %. The median time from transplantation to onset of BO was 15 months. In seven of the 13 patients, the primary symptom was only cough, indicating that cough was an important initial symptom for early diagnosis. The median duration from the onset of BO to the requirement of O2 supplementation was 13 months and the main cause of death was respiratory failure. History of chronic graft-versus-host disease was a significant risk factor. Furthermore, female recipients were at greater risk of BO than male recipients; however, no other previously reported risk factors were detected. It is currently difficult to prevent BO on the basis of the reported risk factors. A novel strategy for the early diagnosis and treatment of BO is required.
    International journal of hematology 03/2014; 99(5). DOI:10.1007/s12185-014-1556-4 · 1.68 Impact Factor
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    ABSTRACT: Follicular lymphoma (FL) of the gastrointestinal tract, particularly duodenal follicular lymphoma (DFL), is a rare variant of FL with indolent clinical behavior, and this disease is included in 2008 WHO classifications. In contrast to nodal follicular lymphoma (NFL), DFL occurs most frequently in the second part of the duodenum, lacks follicular dendritic cell meshworks, and has memory B-cell characteristics. However, its molecular pathogenesis is still unclear. In the present study, we examined 10 DFL, 18 NFL, 10 gastric MALT lymphoma samples by gene expression analysis. Quantitative RT-PCR experiments and immunohistochemical analysis for 72 formalin-fixed, paraffin-embedded tissues from an independent series, including 32 DFL, 19 gastric MALT lymphoma, and 27 NFL samples were performed for validation of microarray data. Gene expression profiles of the 3 lymphoma types were compared using 2,918 differentially expressed genes (DEGs) and results suggested that DFL shares characteristics of MALT lymphoma. Among these DEGs, CCL20, and MAdCAM-1 were up-regulated in DFL and MALT but down-regulated in NFL. In contrast, protocadherin gamma subfamily genes were up-regulated in DFL and NFL. Quantitative RT-PCR and immunohistochemical studies demonstrated concordant results. Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT. We hypothesize that increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis. This article is protected by copyright. All rights reserved.
    Cancer Science 03/2014; DOI:10.1111/cas.12392 · 3.53 Impact Factor
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    ABSTRACT: We recently reported frequent detection of antibiotic-resistant bacteria on the oral mucosa during the period of hematopoietic cell transplantation (HCT) and suggested an association between oral mucositis and antibiotic-resistant bacterial infection. Methicillin-resistant Staphylococcus spp. were frequently detected, and the oral cavity may be a reservoir of the gene mediating methicillin resistance, mecA. Here, we examined the frequency of mecA carriers in patients undergoing HCT. Fifty-nine patients (male (M) = 37, female (F) = 22, 47.3 ± 11.0 years) receiving HCT were enrolled in this study. Buccal swab samples were obtained four times from day -7 to day +20 (once/week), and mecA was detected by PCR. Fifty-two subjects without systemic disease, who completed dental treatment, especially periodontal treatment (M = 21, F = 31, 55.4 ± 14.2 years), were also enrolled as controls and checked for mecA on the oral mucosa. Seventy-six percent (45/59) of the HCT patients carried mecA at least once in the study period (days -7 to +20), while no control subjects had mecA. The frequency of mecA carriers was 19.2 % from days -7 to -1, while it was significantly increased on days +7 to +13 and +14 to +20, with frequencies of 60.9 and 63.2 %, respectively (P < 0.01, ANOVA). mecA was detected in oral mucosa of patients undergoing HCT. The high detection frequency of staphylococci resistant to penicillin and beta-lactams in our recent report was supported.
    Supportive Care in Cancer 02/2014; 22(6). DOI:10.1007/s00520-014-2151-1 · 2.50 Impact Factor
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    ABSTRACT: The relative desirabilities of an unrelated donor with a bidirectional 1-locus mismatch (1MM-Bi), a 1-locus mismatch only in the graft-versus-host direction (1MM-GVH), or a 1-locus mismatch only in the host-versus-graft direction (1MM-HVG) are not yet clear. We analyzed adult patients with leukemia or myelodysplastic syndrome who received a first allogeneic stem cell transplant from an HLA-A, -B, -C, and -DRB1 matched or 1-allele mismatched unrelated donor in Japan. The effects of 1MM-Bi (n=1020), 1MM-GVH (n=83), and 1MM-HVG (n=83) compared with a zero mismatch (0MM) (n=2570) were analyzed after adjusting for other significant variables. The risk of grade 3-4 acute graft-versus-host disease (GVHD) was higher with marginal significance in the 1MM-GVH group than in the 0MM group (hazard ratio, 1.85; P=0.014). However, there was no significant difference in overall or non-relapse mortality between the 1MM-GVH and 0MM groups. There was no significant difference in acute GVHD or overall or non-relapse mortality between the 1MM-HVG and 0MM groups. The risks of acute GVHD and overall mortality were significantly higher in the 1MM-Bi group than in the 0MM group. These findings indicate that unrelated donors with 1MM-GVH and 1MM-HVG are both good candidates for patients without an HLA-matched unrelated donor in a Japanese cohort.
    Biology of Blood and Marrow Transplantation 02/2014; 20(2). DOI:10.1016/j.bbmt.2013.12.063 · 3.35 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2014; 20(2):S253. DOI:10.1016/j.bbmt.2013.12.426 · 3.35 Impact Factor
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    ABSTRACT: Pulmonary complications in patients with hematological malignancies are often caused by infection but are sometimes associated with an underlying disease such as organizing pneumonia (OP). Here, we report a case of life-threatening steroid-resistant OP associated with myelodysplastic syndrome (MDS) and successfully performed allogeneic hematopoietic cell transplantation (HSCT). A 33-year-old female with refractory anemia with excess blasts-1 that had progressed from refractory anemia with ringed sideroblasts and concomitant Sweet's syndrome was admitted. Multiple pulmonary infiltrates were revealed on a chest computed tomography scan, which progressively worsened even after chemotherapy and corticosteroid therapy. No evidence of infection was observed in bronchoalveolar lavage fluid. A histological examination of a transbronchial lung biopsy specimen showed lymphocyte invasion with fibrosis, indicating that the pulmonary infiltrates were OP associated with MDS. Before transplantation, she suffered from respiratory failure and required oxygen supplementation. She developed idiopathic pneumonitis syndrome on day 61 that responded well to corticosteroid therapy, and the OP pulmonary infiltrates improved gradually after HSCT, She was discharged on day 104 and is well without recurrence of OP or MDS 2 years after HSCT.
    SpringerPlus 01/2014; 3:3. DOI:10.1186/2193-1801-3-3
  • Pathology 01/2014; 46:S98. DOI:10.1097/01.PAT.0000454434.00016.90 · 2.62 Impact Factor
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    ABSTRACT: Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into C3H model and CD4+ T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell-derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplant period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with CSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4+ T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2013; DOI:10.1016/j.bbmt.2013.11.018 · 3.35 Impact Factor
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    ABSTRACT: ABSTRACT While the use of PCR-based clonality analysis of formalin-fixed paraffin embedded (FFPE) tissue has recently become widespread, the detection sensitivity for lymphoma subtypes using FFPE samples is not well known. Here, we analyzed T-cell receptor γ chain (TCRG) gene rearrangement clonality in 100 cases of T or NK/T cell lymphoma and examined detection sensitivity according to lymphoma subtypes. Clonality was detected in approximately 80% of the major T-cell lymphoma subtypes: peripheral T-cell lymphoma, not otherwise specified, 84% (21/25 cases); angioimmunoblastic T-cell lymphoma, 71% (15/21 cases); and adult T-cell leukemia/lymphoma, 80% (8/10 cases). The number of clonal peaks differed according to subtype. TCRG gene rearrangement was not detected in 63 cases of B-cell lymphoma or reactive lesions. Thus, clonality analysis can effectively and reliably detect TCRG gene rearrangement in T-cell lymphoma cases and could, therefore, be a useful diagnostic tool in routine practice.
    Leukemia & lymphoma 12/2013; 55(9). DOI:10.3109/10428194.2013.871634 · 2.61 Impact Factor
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    ABSTRACT: Graft-versus-host disease (GVHD) is a major concern in transplantation patients. Gut GVHD is accompanied by diarrhea, abdominal pain, and/or melena. Although oral treatment with corticosteroids (CSs) is effective in treating gut GVHD, it can cause adverse reactions that affect the entire body. Topical administration of CSs can be effective in treating diseases in which lesions are limited locally, because adverse reactions can then be alleviated. In this study, we examine and discuss an enteric-coated beclomethasone dipropionate (BDP) capsule (BDP-EC) formulated at Okayama University Hospital. The BDP-EC did not dissolve in solution 1 (pH1.2), and began disintegrating in solution 2 (pH6.8) after 5min, with a mean dissolution rate at 15min of 85%. We then used the capsule to treat a patient who developed gut GVHD after allogeneic hematopoietic stem cell transplantation. Clinically, the frequency of diarrhea decreased after BDP-EC administration. In addition, we were able to decrease the prednisolone equivalent dose. Symptoms associated with adverse reactions to BDP were not observed during the hospitalization period. These findings suggest that the administration of BDP-EC in the early stages of gut GVHD may allow a reduction in the initial doses of systemic CSs.
    Acta medica Okayama 10/2013; 67(5):319-24. · 0.75 Impact Factor
  • Yoshinobu Maeda
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    ABSTRACT: In addition to reduced-intensity conditioning, which has expanded the eligibility for hematopoietic cell transplantation (HCT) to older patients, increased availability of alternative donors, including HLA-mismatched unrelated donors, has increased access to allogeneic HCT for more patients. However, acute graft-versus-host disease (GVHD) remains a lethal complication, even in HLA-matched donor-recipient pairs. The pathophysiology of GVHD depends on aspects of adaptive immunity and interactions between donor T-cells and host dendritic cells (DCs). Recent work has revealed that the role of other immune cells and endothelial cells and components of the innate immune response are also important. Tissue damage caused by the conditioning regimen leads to the release of exogenous and endogenous "danger signals". Exogenous danger signals called pathogen-associated molecular patterns and endogenous noninfectious molecules known as damage-associated molecular patterns (DAMPs) are responsible for initiating or amplifying acute GVHD by enhancing DC maturation and alloreactive T-cell responses. A significant association of innate immune receptor polymorphisms with outcomes, including GVHD severity, was observed in patients receiving allogeneic HCT. Understanding of the role of innate immunity in acute GVHD might offer new therapeutic approaches.
    International journal of hematology 08/2013; 98(3). DOI:10.1007/s12185-013-1421-x · 1.68 Impact Factor
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    ABSTRACT: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD20 was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor γ chain and/or α-β chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered.
    Human pathology 05/2013; 44(9). DOI:10.1016/j.humpath.2013.03.002 · 2.81 Impact Factor

Publication Stats

1k Citations
369.47 Total Impact Points


  • 2002–2014
    • Okayama University
      • Department of Hematology, Oncology and Respiratory Medicine
      Okayama, Okayama, Japan
  • 2005–2013
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 2009
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2002–2008
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
  • 2002–2006
    • Ehime Prefectural Central Hospital
      Matuyama, Ehime, Japan