Yoshinobu Kanda

Jichi Medical University, Totigi, Tochigi, Japan

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Publications (342)1306.56 Total impact

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    ABSTRACT: Bloodstream infections (BSI) are still important complications following allogeneic hematopoietic stem cell transplantation (allo-SCT). Patients who are receiving corticosteroid therapy can develop BSI without fever. The usefulness of surveillance blood culture in these situations is controversial. We retrospectively analyzed 74 patients who received corticosteroid consisting of >= 0.5mg/kg prednisolone or equivalent following allo-SCT. In principle, we performed surveillance blood culture weekly for these patients. Sixteen patients (21.6%) developed definite BSI. In a multivariate analysis, a myeloablative conditioning regimen (MAC), high-risk disease status at allo-SCT and the presence of a central venous catheter (CVC) at the initiation of corticosteroid therapy were identified as independent significant risk factors for the development of definite BSI. At the first definite BSI episode, seven patients (46.7%) were afebrile and diagnosed by surveillance blood culture. However, 6 of these 7 afebrile patients showed various signs that could be attributable to infection at the time of positive blood culture. In conclusion, patients receiving corticosteroid therapy following allo-SCT frequently develop afebrile BSI. Although surveillance blood culture might be beneficial in these situations, it also seems important to not miss the signs of BSI even when patients are afebrile.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2015; DOI:10.1016/j.bbmt.2015.09.019 · 3.40 Impact Factor
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    ABSTRACT: The effects of intensive regimens and the roles of drugs used might differ between T- and B-lineage acute lymphoblastic leukemia (ALL). We performed a literature search for clinical studies published from January 1998 to March 2013. Studies were eligible for inclusion in the analyses if they included more than 80 patients with adult ALL who were treated with a uniform regimen and compared T- and B-lineage ALL. Studies that included only adolescent or elderly patients were excluded. We identified 11 clinical studies, which included a total of 381 and 1366 patients with T- and B-lineage ALL, respectively, and performed meta-analyses using the selected studies. Nine studies included patients with Philadelphia chromosome-positive (Ph+) ALL. A meta-analysis using the random-effect model demonstrated superior survival in patients with T-lineage ALL compared to those with B-lineage ALL (hazard ratio 1.78, 95 % confidence interval 1.50-2.11), though the inclusion of patients with Ph+ ALL in B-lineage ALL must have influenced this result strongly. We performed meta-regression analyses, adjusted according to whether or not patients with Ph+ ALL were included in each study. Use of dexamethasone (Dex), higher dose of methotrexate (MTX), and higher dose of L-asparaginase (L-asp) were associated with a significant trend toward a better outcome in T-lineage ALL. A meta-regression analysis including Dex and the dose of L-asp or MTX together as covariates showed that these factors were independently significant. In conclusion, the use of Dex and high-dose L-asp or MTX may improve the outcome of T-lineage ALL. This hypothesis should be tested in a prospective study including only patients with Ph-negative ALL.
    Annals of Hematology 09/2015; DOI:10.1007/s00277-015-2510-0 · 2.63 Impact Factor
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    ABSTRACT: Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients.Bone Marrow Transplantation advance online publication, 14 September 2015; doi:10.1038/bmt.2015.205.
    Bone marrow transplantation 09/2015; DOI:10.1038/bmt.2015.205 · 3.57 Impact Factor
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    ABSTRACT: Objective: The purpose of this study was to review the high-resolution computed tomography (CT) findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT), and to evaluate the relationship between CT findings and clinical outcomes. Patients and methods: We collected the clinical data in 96 consecutive patients who underwent CT scan for pulmonary complications after allogeneic HSCT and analyzed the relationships among these clinical characteristics, CT findings and clinical responses. Radiologists who were blinded to clinical information evaluated the CT findings. Results: In multivariate analyses, the presence of chronic graft-versus-host disease (GVHD) and non-segmental multiple consolidations were significantly associated with a poor response to antimicrobial therapies, and the disease risk was significantly associated with a poor corticosteroid response. In addition, the existence of cavity formation and pleural effusion were significantly associated with a fatal prognosis. Twenty-five patients underwent bronchoscopic examination and 4 of them also underwent transbronchial lung biopsy (TBLB), but diagnostic information was not obtained in 15 patients. There was no significant association between specific CT findings and the diagnosis based on bronchoscopic examination. Conclusions: No specific CT finding was identified as a predictor for either an antimicrobial response or for a corticosteroid response in this study. The presence of cavity formation and pleural effusion may predict a poor prognosis.
    European journal of radiology 09/2015; DOI:10.1016/j.ejrad.2015.08.020 · 2.37 Impact Factor
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    ABSTRACT: Objectives The D-index and the L-index, calculated as the area over the neutrophil and lymphocyte curves, respectively, reflect both the intensity and duration of cytopenia. We, retrospectively, investigated the impact of these indexes on pulmonary infection (PI) in induction chemotherapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods We included 92 patients (ALL 83, LBL 9) from two institutions. We calculated the D-index and cumulative D-index until the development of PI (c-D-index), which enables real-time risk assessment for infection. We also calculated the L-index (35), defined as the area over the lymphocyte curve during lymphopenia (<700/µl) until day 35 and the cumulative-L-index until the development of PI (c-L-index). Results Eight patients developed PI on day 20 (median). Two patients were strongly suspected to have bacterial pneumonia, and the others were suspected to have pulmonary fungal infection. The D-index and the L-index (35) in patients with PI were higher than those in patients without PI (7230 ± 4734 vs. 4519 ± 3416, P = 0.041 and 15 458 ± 5243 vs. 8920 ± 5901, P = 0.018), while the c-D-index and the c-L-index were not significantly different. Although the c-L-index did not have predictive value for PI, c-D-index, when treated as a dichotomous variable with a cutoff value of 5589 as determined by a receiver operating characteristic curve analysis, showed a significant difference between two groups (P = 0.045). This association became clearer when we focused on suspected pulmonary fungal infection. Discussion and conclusion In induction chemotherapy for ALL/LBL, c-D-index with a cutoff value of 5589 might have predictive value for the development of PI.
    Hematology (Amsterdam, Netherlands) 09/2015; DOI:10.1179/1607845415Y.0000000051 · 1.25 Impact Factor
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    ABSTRACT: Addition of high-dose cytarabine (HDCA) to the conventional cyclophosphamide/total-body irradiation (CY/TBI) regimen significantly improved prognosis after cord blood transplantation (CBT) for adult acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The efficacy of HDCA in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), however, has not yet been elucidated. We conducted a cohort study to compare the prognosis of HDCA/CY/TBI (N = 435) and CY/TBI (N = 1667) in BMT/PBSCT for AML/MDS using a Japanese transplant registry database. The median age was 38 years, and 86.0 % of the patients had AML. Unrelated donors comprised 54.6 %, and 63.9 % of donors were human leukocyte antigen (HLA)-matched. Overall survival (OS) was not improved in the HDCA/CY/TBI group (adjusted hazard ratio (HR), 1.14; p = 0.13). Neutrophil engraftment was inferior (HR, 0.80; p < 0.01), and the incidence of hemorrhagic cystitis and thrombotic microangiopathy increased in HDCA/CY/TBI (HR, 1.47 and 1.60; p = 0.06 and 0.04, respectively), leading to significantly higher non-relapse mortality (NRM; HR, 1.48; p < 0.01). Post-transplant relapse and tumor-related mortality were not suppressed by the addition of HDCA. This study indicated the inefficacy of HDCA/CY/TBI in BMT/PBSCT for AML/MDS. Our results should be validated in large-scale prospective studies.
    Journal of Hematology & Oncology 09/2015; 8(1):102. DOI:10.1186/s13045-015-0201-x · 4.81 Impact Factor
  • Yukie Tanaka · Yoshinobu Kanda
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    ABSTRACT: ATL is an aggressive T-cell malignancy caused by HTLV-1 virus infection. Tax, which is the most important regulatory protein of HTLV-1, is associated with aggressive proliferation of host cells and is also a major target antigen for CD8(+) cytotoxic T-cells (CTLs). Recently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven effective for ATL, and donor-derived Tax-specific CTL might contribute to graft-versus-ATL effects in some recipients who maintained complete remission after allo-HSCT. We, for the first time, analyzed the Tax-specific T-cell receptor (TCR) repertoire, phenotypes and functions of Tax-specific CTLs at single-cell levels in HLA-A24(+) ATL patients who underwent allo-HSCT. We found that 1) a particular amino acid sequence motif (PDR) in the CDR3 region of TCR-β was conserved in different patients and also within the same patient before and after allo-HSCT, and 2) the PDR(+) Tax-specific CTL clone selectively expanded in ATL long-term survivors as less-differentiated effector memory CTLs. Actually, the PDR(+) CTL showed not only strong binding activity for the Tax-tetramer but also strong killing activity against patients' HTLV-1-infected T-cells without any reaction against normal cells. We are presently evaluating the killing activities of PDR(+)TCR-transduced T-cells against Tax in immunodeficient mice, with the aim of developing a new immunotherapy for ATL.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 08/2015; 56(7):815-24. DOI:10.11406/rinketsu.56.815
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    ABSTRACT: Tyrosine kinase inhibitor (TKI) treatment has dramatically improved the outcome of chronic myelogenous leukemia in the chronic phase (CML-CP). However, one study has reported a less favorable treatment outcome with TKIs in adolescents and young adults (AYA) when compared with older patients. In the present study, we retrospectively reviewed the response to TKIs in a Japanese population of 133 CML-CP patients divided into an AYA group (n = 19) and an older group (n = 114). At diagnosis, AYA patients presented with higher white blood cell counts and lower percentage of basophils, and with lower Hasford scores, but no difference was observed in EUTOS score. Probability of achieving complete cytogenetic response was not statistically different between the groups. However, the probabilities of achieving major and complete molecular responses were significantly lower in the AYA group compared to the older group (61 vs 87 % and 17 vs. 33 % at 24 months, respectively; P < 0.05). In addition, a 7-year event-free survival was significantly lower in the AYA compared to the older adults (58 vs. 80 %, P < 0.05). These results suggest that AYA Japanese patients with CML-CP tend to have an unfavorable outcome on treatment with TKI.
    International journal of hematology 07/2015; 102(3). DOI:10.1007/s12185-015-1840-y · 1.92 Impact Factor
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    ABSTRACT: Allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with relapsed follicular lymphoma (FL). Prospective studies of reduced-intensity conditioning (RIC) have revealed that chemosensitivity at allo-SCT is the most reliable predictor of outcome; however, limited data are available for progressive/refractory disease. We report here a retrospective analysis of RIC allo-SCT for patients with FL. The purpose of this study was to elucidate the role of allo-SCT for patients with relapsed/refractory FL. We analyzed 46 patients-11 (24%) transplanted in CR, 6 (13%) transplanted in PR and 29 (63%) with progressive/refractory disease. The estimated 5-year overall survival rate was 71.6% (95% confidence interval (CI), 51.5-84.5%). According to the disease status at transplantation, the 5-year survival rate was 80.7% (95% CI, 37.7-95.4%) in the patients with CR or PR and 66.1% (95% CI, 41.5-82.3%) in those with progressive/refractory disease (P=0.29). There were no differences in relapse/progression and non-relapse mortality between the patients with chemosensitive disease and progressive/refractory disease. Allo-SCT may be a valuable treatment option, even for patients with progressive/refractory FL.Bone Marrow Transplantation advance online publication, 13 July 2015; doi:10.1038/bmt.2015.158.
    Bone marrow transplantation 07/2015; DOI:10.1038/bmt.2015.158 · 3.57 Impact Factor
  • Kazuo Tamura · Nobu Akiyama · Yoshinobu Kanda · Masahiro Saito
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    ABSTRACT: Tazobactam/piperacillin (4.5 g for adults and 90 mg/kg body weight for children, every 6 h) was administered to Japanese patients with febrile neutropenia to evaluate its defervescence and clinical efficacy and safety. The pharmacokinetics in children were also examined. Defervescence efficacy at day 4 of the treatment was achieved in 50.0% of 94 adult and 62.5% of 8 pediatric patients, respectively. The defervescence efficacy rate in relation to the neutrophil count in adults was 37.5% for the patients with a neutrophil count of less than 100/μL and 62.5% for that between 100 and 500/μL. The clinical efficacy rate at day 7 and at the end or discontinuation of the treatment was 79.6% and 59.1% in adult patients, respectively, and 57.1% and 75.0% in pediatric patients, respectively. Fifteen strains of causative bacteria were isolated in 13 adult patients at baseline. All strains were eradicated within 4 days of the treatment. The side effects that occurred in adult and pediatric patients during the treatment were all known and not specific to febrile neutropenia patients. The pharmacokinetics profiles of tazobactam/piperacillin in children with febrile neutropenia are unlikely to be different from those in children with a common bacterial infection and without any immunosuppressive conditions. The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults. As for pediatric patients, given the limited number of cases studied, further investigation is needed (Clinical trial number: Japic CTI-121728). Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Journal of Infection and Chemotherapy 06/2015; 21(9). DOI:10.1016/j.jiac.2015.05.009 · 1.49 Impact Factor
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    ABSTRACT: Limited data are available on prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) disease following autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively reviewed the clinical charts of 105 consecutive patients who underwent their first auto-HCT at our institution between September 2007 and June 2014. Before August 2009, 30 patients received oral acyclovir at 1000 mg/day until engraftment, whereas after September 2009, 69 patients received oral acyclovir at 200 mg/day. After engraftment, acyclovir was continued at 200 mg/day at the discretion of the attending physicians in both groups. The cumulative incidence of HSV disease at 1 year after auto-HCT was 7.7 and 4.5 % in patients who received oral acyclovir at 1000 and 200 mg/day, respectively (P = 0.75). Patients were next divided into three groups according to the timing at which acyclovir prophylaxis was stopped after auto-HCT; at engraftment, between engraftment and 1 year after auto-HCT, and later than 1 year. The cumulative incidence of VZV disease was 25.8, 7.7, and 0.0 % at 1 year, respectively. This study suggests that low-dose acyclovir prophylaxis may be effective for preventing HSV and VZV disease after auto-HCT. Our findings support the recommendation of acyclovir prophylaxis within the first year after auto-HCT.
    International journal of hematology 05/2015; 102(2). DOI:10.1007/s12185-015-1810-4 · 1.92 Impact Factor
  • Physiotherapy 05/2015; 101:e1015-e1016. DOI:10.1016/j.physio.2015.03.1883 · 1.91 Impact Factor
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    ABSTRACT: This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical RIST using a low dose of ATG and steroid was conducted in 5 institutes in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic SCT. The conditioning regimen consisted of fludarabine, busulfan and anti-T-lymphocyte globulin (Fresenius, 8 mg/kg), and GVHD prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except one (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > 0.5 x 10(9)/l on day 11 and platelets > 20 x 10(9)/l on day 17.5. Treatment was started for ≥ grade I GVHD, and the cumulative incidence of acute grade I and grade II-IV GVHDs was 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after the transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with CR/CP (n=8) and non-CR (n=26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (p=0.0424), which tended to have a lower survival rate (p=0.0524). This transplant protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse but not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or DLI may be desirable for patients with non-CR status. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2015; 21(8). DOI:10.1016/j.bbmt.2015.04.012 · 3.40 Impact Factor
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    ABSTRACT: The relative importance of the resolution level of HLA typing has not been fully defined for related donor transplantation. To address this question, we retrospectively evaluated patients who underwent a first related hematopoietic stem cell transplantation (HSCT) from 2000 to 2011 from an HLA high-resolution matched (MRD, n=2244), high-resolution 1 locus-mismatched (HR-MMRD, n=116), or low-resolution 1 locus-mismatched related donor (LR-MMRD, n=396) in the graft-versus-host direction at 3 loci (HLA A, B and DRB1) using the database of the Japan Society for Hematopoietic Cell Transplantation. The median age was 40 years (0-74). The median follow-up duration of surviving patients was 950 days. Although the cumulative incidences of grade III-IV acute graft-versus-host disease (GVHD) in the HR-MMRD and LR-MMRD groups were significantly higher than those in the MRD group (HR-MMRD 19.8%, LR-MMRD 20.4%, and MRD 9.5%), there was no statistically significant difference between the HR-MMRD and LR-MMRD groups (P=0.65). Although both HR-MMRD and LR-MMRD were significantly associated with an increased risk of non-relapse mortality and a worse overall survival, there was no statistically significant difference between the HR-MMRD and LR-MMRD groups. In conclusion, LR-MM and HR-MM have a similar adverse impact on the outcome in related HSCT. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    American Journal of Hematology 04/2015; 90(7). DOI:10.1002/ajh.24028 · 3.80 Impact Factor
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    ABSTRACT: We evaluated the incidence of and risk factors for false-positive Aspergillus galactomannan (GM) antigenemia in allogeneic hematopoietic stem cell transplantation (HSCT). We also focused on the GM index value and its kinetics. Patients who underwent their first allogeneic HSCT at our center between June 2007 and December 2012 were included (n=172). Episodes of positive GM tests were classified as either "true-positive", which fulfilled the EORTC criteria for proven or probable invasive aspergillosis (IA), or "false-positive", which was not accompanied by clinical findings. The remaining cases were regarded as "inconclusive". The one-year cumulative incidences of IA and positive GM tests were 10.1% and 48.1%, respectively. Among 148 episodes of positive GM tests, 97(65.5%), 23(15.5%), and 28(19.0%) were classified as false-positive, true-positive and inconclusive, respectively. In the first episodes of positive GM tests in each patient (false-positive=67, others=30), an increase in the GM value in the first two measurements, neutropenia, and use of anti-mold agents at positive GM episode were associated with a significantly lower possibility of false-positive results according to a multivariate analysis. A false-positive GM test was frequently seen after allogeneic HSCT. An increase in the GM value may increase its positive predictive value. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
    Journal of Infection 03/2015; 70(5). DOI:10.1016/j.jinf.2015.02.012 · 4.44 Impact Factor
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    ABSTRACT: This prospective study aimed to investigate the influence of pretransplant serum ferritin levels on the outcomes of allogeneic hematopoietic SCT (HSCT). In total, 190 patients with acute leukemia or myelodysplastic syndrome were consecutively enrolled. The patients were divided into two groups: low-ferritin group (<1000 ng/mL) and high-ferritin group (⩾1000 ng/mL). The primary end point was the cumulative incidence of infection within 100 days after HSCT, which was similar between the two groups: bloodstream infection, 35 vs 38%, P=0.65; bacterial infection, 44 vs 41%, P=0.68; and fungal infection, 6 vs 8%, P=0.71. The 1-year adjusted probability of OS of the high-ferritin group was significantly lower than that of the low-ferritin group (76 vs 63%, P=0.017). Using receiver operating characteristic curve, the threshold of pretransplant serum ferritin levels for bloodstream infection was 1400 ng/mL; the threshold for OS, EFS and non-relapse mortality was 1349 ng/mL. In conclusion, pretransplant serum ferritin levels of ⩾1000 ng/mL did not influence the incidence of infection but adversely affected OS after HSCT. A higher threshold of pretransplant serum ferritin levels may predict HSCT outcomes.Bone Marrow Transplantation advance online publication, 2 March 2015; doi:10.1038/bmt.2015.17.
    Bone Marrow Transplantation 03/2015; 50(5). DOI:10.1038/bmt.2015.17 · 3.57 Impact Factor
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    ABSTRACT: Cord blood has been investigated as an alternative source for hematopoietic stem cell transplantation, but information about its use for multiple myeloma is limited. The purpose of this study was to evaluate the feasibility of cord blood transplantation (CBT) for patients with multiple myeloma. Eighty-six patients with multiple myeloma who underwent a first CBT between 2001 and 2011 were included in this retrospective study. Sixty-two of them had received other types of stem cell transplantation before CBT. The cumulative incidences of neutrophil engraftment at day 50, grade II-IV acute GVHD, and chronic GVHD were 81.4%, 39.0%, and 19.5%, respectively. The incidence of non-relapse mortality (NRM) at 2 years was 39.0%, but it was only 6.2% in patients who underwent planned tandem autologous/reduced-intensity conditioning CBT (auto/RIC-CBT). Progression-free survival (PFS) and overall survival (OS) at 6 years were 13.0% and 15.2%, respectively. Less than a partial response before CBT and lack of prior transplantation were independent significant adverse factors for PFS, whereas the presence of prior transplantation and planned tandem transplantation were associated with better OS. OS at 6 years in patients who underwent auto/RIC-CBT was 45.9%. In addition, the development of chronic GVHD was associated with superior PFS. In conclusion, we demonstrated that cord blood is feasible as an alternative graft source for myeloma patients. Although CBT provided long-term survival for a fraction of patients, optimal use of this graft requires further clinical studies. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2015; 21(7). DOI:10.1016/j.bbmt.2015.02.015 · 3.40 Impact Factor
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    ABSTRACT: In Japan, intravenous busulfan (ivBu) is usually given four times per day as an infusion at 0.8 mg/kg over 2 h. However, as this requires a midnight administration, a once-daily infusion of ivBu at 3.2 mg/kg over 3 h has been investigated as a more convenient and safer method. In this study, 20 Japanese patients received once-daily ivBu in conditioning regimens before allogeneic hematopoietic stem cell transplantation (HSCT), and blood samples were obtained just before, and 3, 3.5, 5, 7, 10, and 24 h after the initiation of ivBu infusion. The outcomes of HSCT were evaluated prospectively. The median area under the plasma concentration versus time curve (AUC) of Bu was 5272 μmol × min/L (range 3491-6284 μmol × min/L), and was similar to those in previous once-daily ivBu studies and to the estimated daily AUC in previous 4-times-daily ivBu studies. All of the patients but two, who died early due to infection, achieved neutrophil engraftment at a median of 25 days after transplantation. No patient was diagnosed with veno-occlusive disease according to the criteria established by Jones. No regimen-related toxicity was significantly associated with AUC. In conclusion, once-daily administration of ivBu has a stable pharmacokinetic profile, and was safely performed in Japanese patients.
    International Journal of Hematology 02/2015; 101(5). DOI:10.1007/s12185-015-1756-6 · 1.92 Impact Factor
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    ABSTRACT: The relative desirability 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) is 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 grades III to IV 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=.014). However, there was no significant difference in overall or nonrelapse mortality between the 1MM-GVH and 0MM groups. There was no significant difference in acute GVHD or overall or nonrelapse 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: journal of the American Society for Blood and Marrow Transplantation 02/2015; 21(2):305-311. DOI:10.1016/j.bbmt.2014.10.015 · 3.40 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S159-S160. DOI:10.1016/j.bbmt.2014.11.229 · 3.40 Impact Factor

Publication Stats

5k Citations
1,306.56 Total Impact Points


  • 2008–2015
    • Jichi Medical University
      • Division of Hematology
      Totigi, Tochigi, Japan
  • 2014
    • Saitama Medical University
      • Department of Hematology and Oncology
      Saitama, Saitama, Japan
  • 1995–2011
    • The University of Tokyo
      • • Department of Hematology and Oncology
      • • Department of Cell Therapy and Transplantation Medicine
      • • Division of Internal Medicine
      Edo, Tōkyō, Japan
  • 2000–2008
    • Tokyo Medical University
      • Division of Hematology
      Edo, Tōkyō, Japan
    • National Institute for Basic Biology
      Okazaki, Aichi, Japan
  • 2007
    • Yokohama City University
      • Department of Hematology
      Yokohama, Kanagawa, Japan
  • 1999–2007
    • High Energy Accelerator Research Organization
      • Radiation Science Research Center
      Tsukuba, Ibaraki, Japan
  • 2006
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka, Ōsaka, Japan
  • 2001–2006
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 2004
    • Nagasaki University
      Nagasaki, Nagasaki, Japan
  • 2001–2003
    • National Cancer Center, Japan
      • Endoscopy Division
      Edo, Tōkyō, Japan
  • 2000–2001
    • Toranomon Hospital
      Edo, Tōkyō, Japan
  • 1998–2000
    • Meikai University
      • Department of Dental Pharmacology
      Саитама, Saitama, Japan
  • 1997–1999
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan