Yoshinobu Kanda

Saitama Medical University, Saitama, Saitama, Japan

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Publications (311)1184.92 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytomegalovirus (CMV)-specific CD8(+) cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear. Using a single-cell T-cell receptor repertoire analysis, we monitored clones and chimerism of CMV-CTLs in 3 CMV-seropositive alloHCT recipients from CMV-seronegative donors, with or without CMV reactivation. Nearly all of the CMV-CTLs during follow-up were CD45RA(-) CCR7(-) effector memory/CD45RA(+) CCR7(-) effector T cells, and were highly matured. In each case, the use of BV gene families was restricted, especially in BV5, 7, 28, and 29. Although no common predominant CMV-CTL clones were found, several shared motifs of complementarity-determining region-3 were identified among the 3 cases; QGA in all, TGE and TDT in Case 1 and Case 2, and RDRG in Case 2 and Case 3. In all cases, CMV-CTL clones that were detected for the first time after alloHCT persisted as the dominant clones. In Case 1, without CMV reactivation, recipient-derived CMV-CTLs exclusively persisted as a dominant clone, while all CMV-CTLs in the other 2 cases, with CMV reactivation, were donor derived. Clone monitoring and chimerism analyses should help to further clarify novel aspects of immuno-reconstitution after alloHCT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Transplant Infectious Disease 11/2014; · 1.98 Impact Factor
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    ABSTRACT: Elderly patients with non-Hodgkin lymphoma (NHL) have a poor prognosis. Owing to treatment-related toxicities, there is no standard chemotherapy for the elderly patients, especially those aged 70 years or older. In this study, we retrospectively evaluated the efficacy and toxicity of reduced-dose (two-thirds) R-CHOP chemotherapy as an initial chemotherapy for 45 patients aged 70 years or older with B-cell NHL. The WHO classification of NHL included diffuse large B-cell lymphoma (DLBCL) (31), mantle cell lymphoma (5), follicular lymphoma (4), extranodal marginal zone lymphoma (1), Burkitt lymphoma (1), and B-cell lymphoma whose further types were unclassified (3). The incidences of grade 4 neutropenia and febrile neutropenia (FN) were 51·1 and 15·6%, respectively. Efficacy was evaluated in patients with DLBCL. The overall and complete response (CR) rates were 96·7 and 90·0%, respectively. Two-year event-free survival (EFS) and overall survival (OS) were 84·4 and 89·2%, respectively. There was no treatment-related mortality. In conclusion, two-thirds R-CHOP chemotherapy is a promising treatment for elderly patients with B-cell NHL in terms of its efficacy and toxicity.
    Journal of chemotherapy (Florence, Italy) 10/2014; · 0.83 Impact Factor
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    ABSTRACT: Background Cytomegalovirus (CMV) reactivation still remains a major problem following allogeneic hematopoietic stem cell transplantation (HSCT).Patients and methodsIn this study, we analyzed an immunoglobulin allotype, IgG1m(f), in CMV-seropositive HSCT recipients and their donors to distinguish donor-derived antibody from recipient-derived antibody. Eight donor-recipient pairs were informative regarding the appearance of donor-derived immunoglobulin-G (IgG), as the recipients were homozygous null for the IgG1m(f) allotype and the donors were IgG1m(f) positive. In these patients, total IgG, IgM, and allotype-specific IgG against CMV were measured by enzyme-linked immunosorbent assay. All subjects were monitored for at least 9 months after HSCT with (n = 5) or without (n = 3) CMV reactivation.ResultsDonor-derived CMV IgG tended to be elevated earlier in patients with CMV-seropositive donors than in those with CMV-seronegative donors. In 1 patient with a CMV-negative donor, donor-derived CMV IgG was not detected until late CMV reactivation. In 3 patients without CMV reactivation, donor-derived CMV IgG was also elevated within 1–6 months after HSCT.Conclusion In conclusion, the CMV serostatus of the donor may be related to the timing of the appearance of donor-derived CMV IgG and the reconstitution of humoral immunity against CMV, regardless of the CMV antigenemia level after HSCT.
    Transplant Infectious Disease 10/2014; · 1.98 Impact Factor
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    ABSTRACT: We report a case of severe oral infection with a high fever due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia. The patient did not improve on treatment with meropenem, clindamycin, or vancomycin until neutrophil recovery. Since L. rhamnosus GG is used in dairy products, and the patient ingested dairy products daily before starting chemotherapy, we suspected an association between the ingestion of dairy products and the development of infection. Pulsed-field gel electrophoresis using two different restriction enzymes showed that the strain isolated from the patient was identical to the L. rhamnosus GG strain isolated from dairy products and ATCC #53103. This was confirmed by a PCR assay with species-specific L. rhamnosus GG primers. Since Lactobacillus infection, particularly L. rhamnosus infection, can be fatal in immunocompromised hosts, we should consider Lactobacillus as a causative organism when Gram-positive rods are detected during treatment with broad-spectrum antibiotics and vancomycin. The causal association between the ingestion of dairy products containing Lactobacillus and Lactobacillus infection in immunocompromised hosts warrants further study.
    International journal of hematology. 08/2014;
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    ABSTRACT: In unrelated hematopoietic SCT (HSCT), HLA allele mismatch has been shown to have a significant role. To clarify the importance of HLA allele mismatch in the GVH direction in related HSCT, we retrospectively evaluated 2377 patients who received stem cells from an HLA serologically matched related donor in the GVH direction using the database of the Japan Society for Hematopoietic Cell Transplantation. The cumulative incidences of grade II-IV and grade III-IV acute GVHD in patients with an HLA allele-mismatched donor (n=133, 5.6%) were significantly higher than those in patients with an HLA allele-matched donor. Multivariate analyses showed that the presence of HLA allele mismatch was associated with increased risks of grade II-IV and grade III-IV acute GVHD. In particular, HLA-B mismatch and multiple allele mismatches were associated with an increased risk of acute GVHD. The presence of HLA allele mismatch was associated with an inferior OS owing to an increased risk of non-relapse mortality (NRM). In conclusion, the presence of HLA allele mismatch in the GVH direction in related HSCT was associated with increased risks of GVHD and NRM, which led to an inferior OS. HLA allele typing is recommended in related HSCT.Bone Marrow Transplantation advance online publication, 7 July 2014; doi:10.1038/bmt.2014.141.
    Bone marrow transplantation. 07/2014;
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    ABSTRACT: Background Previous studies have shown that most patients lose immunity to measles, mumps, and rubella (MMR) during long-term follow-up after allogeneic hematopoietic stem cell transplantation (HSCT), and immunizations against them have been investigated. However, these previous studies mainly targeted pediatric patients and information in adult patients is still insufficient. Methods We evaluated the immunity to MMR in 45 adult allogeneic HSCT patients. None of these patients received vaccination after HSCT. Results The seropositive rates at six years after allogeneic HSCT were estimated to be less than 44% for measles, less than 10% for mumps, and less than 36% for rubella. Thirteen of the 16 female patients who were 16-39 years old were negative or equivocal for rubella. Patients who developed grade II-IV acute graft-versus-host disease tended to become seronegative for measles and rubella at two years after HSCT, although the difference was not statistically significant. Conclusions This study showed that most adult patients lost immunity to MMR after allogeneic HSCT. Although we did not evaluate the safety and efficacy of vaccination in this study, most HSCT guidelines recommend vaccination for HSCT recipients without active chronic graft-versus-host disease or ongoing immunosuppressive therapy at 24 months after HSCT. Immunization against rubella is especially important for female patients of reproductive age. Further studies will be necessary to evaluate the effect of vaccination on the antibody response in adult allogeneic HSCT recipients.
    Hematology (Amsterdam, Netherlands) 07/2014; · 1.33 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). · 3.94 Impact Factor
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    ABSTRACT: Conditioning regimens consisting of reduced-dose cyclophosphamide (CY) and fludarabine (FDR) have been investigated for use in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia to reduce the toxicities associated with CY. However, the ideal dose of CY has not been identified. In addition, little information is available regarding donor cell chimerism after allo-HSCT with these regimens. Therefore, we retrospectively analyzed 13 patients who underwent allo-HSCT with half-dose CY (100 mg/kg in total), FDR, and anti-thymocyte globulin at total doses of 2.5-10 mg/kg at our center. All the patients except one, who died due to encephalopathy on day 20, achieved neutrophil engraftment a median of 18.5 days after HSCT with complete donor-type chimerism. Two patients who received a graft from an HLA-matched donor subsequently developed mixed chimerism (MC) associated with transfusion-dependent cytopenia. One became transfusion-independent after donor lymphocyte infusion, but continues to exhibit MC. The other regained complete donor-type chimerism after the cessation of cyclosporine, but remains transfusion-dependent. These findings suggest that a conditioning regimen with half-dose CY and FDR is effective for achieving neutrophil engraftment and complete donor-type chimerism. However, subsequent MC may be observed, especially after HLA-matched HSCT.
    International journal of hematology 02/2014; · 1.17 Impact Factor
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    ABSTRACT: We previously reported that the baseline C-reactive protein level did not predict infectious events after hematopoietic cell transplantation (HCT). Procalcitonin (PCT) has recently emerged as a powerful biomarker for the early diagnosis of bacterial infection. We evaluated the ability of the baseline PCT level to predict early infectious events after HCT in 79 recipients who received HCT between 2008 and 2012. The high-PCT group (0.07 ng/mL, n=27) frequently experienced documented infection (DI) (21.2% vs 44.4% at day 30, P=0.038) and bloodstream infection (BSI) (15.4% vs 37.0% at day 30, P=0.035). In a multivariate analysis, however, the baseline PCT level was not significantly associated with DI (HR 2.01, P=0.089) or BSI (HR 2.28, P=0.084). Localized infection, such as anal canal problems, before the start of conditioning was seen in 26 patients. When we stratified the patients according to the presence of elevated PCT and localized infection, the group with elevated PCT and localized infection (n=17) was significantly associated with increased DI (HR 3.40, P=0.0074) and BSI (HR 3.59 P=0.0078) after HCT. A larger prospective observation is warranted to confirm the impact of the baseline PCT level and clinical features on the outcome of HCT.Bone Marrow Transplantation advance online publication, 13 January 2014; doi:10.1038/bmt.2013.217.
    Bone marrow transplantation 01/2014; · 3.00 Impact Factor
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    ABSTRACT: Adiponectin has been shown to play a critical role in immunity. Recently, we reported that the adiponectin levels after allogeneic stem cell transplantation (SCT) were higher in recipients with chronic graft-versus-host disease (cGVHD). However, the effects of adiponectin on extracellular matrix (ECM) and regulatory factors in dermal fibroblasts remain unclear. We compared the mRNA levels of collagen type1 (COL1A), fibronectin 1 (FN1), MMP1, -3, TIMP1, -3, TGF-β, and TGF-β receptor2 (TGF-βR2) in human normal dermal fibroblasts cultured with and without adiponectin, and assessed the degree of synthesis of ECMs by immunofluorescent microscopy. Furthermore, we also assessed these mRNA levels after blocking of TGF-βR2. Adiponectin induced higher mRNA levels of FN1, MMP1,-3, TIMP1,-3, and TGF-βR2 in a dose-dependent manner, but did not significantly affect COL1A orTGF-β. In addition, adiponectin was shown to up-regulate FN1, MMPs, and TIMPs after blocking of TGF-βR2. Immunofluorescent microscopy revealed that adiponectin promoted a greater synthesis of ECMs than in the control in vitro. The finding that adiponectin up-regulated ECM-associated factors might mean that high levels of adiponectin could modulate dermal fibrosis observed in recipients with cGVHD. A further basic investigation is warranted to elucidate whether the adiponectin-pathway could be a target for the treatment of sclerotic cGVHD.
    Experimental hematology 01/2014; · 3.11 Impact Factor
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    ABSTRACT: Adult T cell leukemia/lymphoma (ATL) is an aggressive mature T cell malignancy that is causally associated with human T cell lymphotropic virus type 1 (HTLV-1) infection. The HTLV-1 regulatory protein Tax aggressively accelerates the proliferation of host cells and is also an important target antigen for CD8(+) cytotoxic T cells (CTLs). We previously reported that several predominant HLA-A*24:02-restricted HTLV-1 Tax301-309-specific CTL clones commonly expressed a particular amino acid sequence motif (P-D-R) in complementarity-determining region 3 of T-cell receptor (TCR)-β chain among unrelated ATL patients who underwent allogeneic stem cell transplantation (allo-HSCT). Furthermore, a PDR-motif(+) CTL clone persistently existed in a long-term survivor as a central CTL clone with strong CTL activities after HSCT. Although a larger analysis of the relationship between PDR-motif(+) CTLs and the clinical course is required, the expression of PDR-motif(+) TCR on CD8(+) T cells may play a critical role in the management of anti-HTLV-1 activities for HLA-A24:02(+) ATL patients. Therefore, in this study, we prepared an HTLV-1 Tax301-309 peptide-specific CTL clone (HT-9) expressing PDR-motif(+) TCR isolated from a long-term survivor after HSCT, and evaluated its CTL activity against a variety of HTLV-1-infected T-cells from HLA-A*24:02(+) ATL patients. Before the assay of CTL function, we confirmed that HT-9 expressed less-differentiated effector-memory phenotypes (CD45RA(-)CCR7(-)CD27(+)CD28(+/-)CD57(+/-)) and T-cell exhaustion marker PD-1(+). In assays of CTL function, HT-9 recognized HTLV-1 Tax in an HLA-restricted fashion and demonstrated strong CTL activities against a variety of HTLV-1-infected T-cells from HLA-A*24:02(+) ATL patients regardless of whether the sources were autologous or allogeneic, but not normal cells. These data indicate that PDR-motif(+) TCR could be an important TCR candidate for TCR-gene immunotherapy for HLA-A24:02(+) ATL patients, provided that the CTL activities against HTLV-1 are reproduced in in vivo experiments using mouse models.
    Immunology letters 01/2014; · 2.91 Impact Factor
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    ABSTRACT: Because the efficacy of donor lymphocyte infusion (DLI) for acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains uncertain, especially in the Asian population, a nationwide registry study was retrospectively performed by the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) to identify the factors affecting the patient survival after DLI. Among 143 adult AML patients who received DLI for the treatment of the first hematological relapse after HSCT, the overall survival (OS) rates at one year, two years and five years were 32% ± 4%, 17% ± 3% and 7% ± 3% respectively. Complete remission (CR) at the time of DLI, which was obtained in 8% of the patients, was the strongest predictive factor for survival after DLI. Therefore, long-term survival after DLI was achieved almost exclusively in patients who successfully achieved a CR prior to DLI, indicating the limited efficacy of DLI in a minority of patients.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 01/2014;
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    ABSTRACT: Recent advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) have led to increasing use of this modality in older patients who tend to have been more heavily pretreated, and have more comorbidities. Thus, the evaluation of comorbidity is of increasing importance to more precisely assess the benefits and risks of the transplant procedure. Researchers from Seattle have developed the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) that was associated with the risk of mortality in several retrospective studies. However, its clinical utility has not been extensively documented in prospective studies. The aim of the present study was to evaluate the utility of the HCT-CI prospectively in a multicenter setting. Overall survival (OS) and non-relapse mortality (NRM) at 2 years was 59% and 20%, respectively (n=243). We found that the HCT-CI in its original scale failed to predict OS and NRM in this set of patients. Thus, we applied a flexible HCT-CI risk scoring system (re-stratified low-risk, defined as score 0-3, and a high-risk score: 4 or higher). The flexible HCT-CI was found to predict 2-year NRM and OS better than the original HCT-CI (NRM: p=0.01, OS: p=0.003). In subgroup analysis, we evaluated the usefulness of the original HCT-CI with patients excluding cord blood (n=186). Both 2y-OS and 2y-NRM were not significantly different according to the original HCT-CI (p=0.304, p=0.996), but with the flexible HCT-CI, there were significant differences in 2y-OS and 2y–NRM (p=0.005, p=0.005). Multivariate analysis identified age >50, performance status (PS) <90, donor type (HLA-mismatched/unrelated donor), and the flexible HCT-CI ≥4 as significant predictors for worse OS at 2 years. However, the flexible HCT-CI did not remain a significant predictor for NRM at 2 years in multivariate analysis, whereas age, PS and donor type did. The HCT-CI did not consistently predict both NRM and OS, but it still can be a useful tool in combination with other factors such as PS and age. Furthermore, the HCT-CI, although potentially useful for capturing pre-transplant comorbidity and risk-assessment, may need further validation prior to its adoption for routine clinical use.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 01/2014;
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    ABSTRACT: Risk of relapse during the unrelated donor coordination period biases comparisons between allogeneic hematopoietic stem cell transplantation from an HLA 8 of 8 allele-matched unrelated donor (8/8 MUD) and that from a related donor with an HLA-1 antigen mismatch in the graft-versus-host (GVH) direction (RD/1AGMM-GVH). To reduce this bias, we performed a decision analysis focusing on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The primary outcome measure was 5-year survival probability with or without quality-of-life (QOL) adjustment. A baseline analysis showed that the decision to perform MUD transplantation was superior to that to perform RD/1AGMM-GVH transplantation for patients with AML or ALL. However, in the ALL cohort, the direction of superiority was reversed when the interval between CR1 and 8/8 MUD transplantation was >5.5 months (without QOL adjustment) or >6 months (after QOL adjustment) or when overall survival of RD/1AGMM-GVH transplantation improved by 1.3% without QOL adjustment and 2.1% after QOL adjustment. In conclusion, 8/8 MUD should be prioritized in transplantation for AML and ALL in CR1. However, the MUD coordination period and improvements in RD/1AGMM-GVH transplantation might change the donor selection priority in transplantation for ALL in CR1.Blood Cancer Journal (2014) 4, e263; doi:10.1038/bcj.2014.85.
    Blood Cancer Journal 01/2014; 4:e263. · 1.40 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 01/2014; · 3.15 Impact Factor
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    ABSTRACT: Objectives We performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients. Methods We collected reports from PubMed, the Cochrane Library, EMBASE, CINAHL, and Web of Science, along with references cited therein. We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. Results Seventeen trials with 1453 autologous and allogeneic HSCT recipients were included. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotics in two trials. Systemic antibiotics other than fluoroquinolones were evaluated in five of these 12 trials. Four trials evaluated the effect of the addition of antibiotics for gram-positive bacteria to fluoroquinolones. One trial compared two different systemic antibiotic regimens: fluoroquinolones versus trimethoprim-sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95%CI 0.09-0.30), clinically or microbiologically documented infection (OR 0.38; 95%CI 0.22-0.63) and bacteremia (OR 0.31; 95% CI 0.16-0.59) without significantly affecting all-cause mortality or infection-related mortality. Conclusions Systemic antibiotic prophylaxis successfully reduced the incidence of infection. However, there was no significant impact on mortality. The clinical benefits of prophylaxis with fluoroquinolones were inconclusive because of the small number of clinical trials evaluated.
    The Journal of infection 01/2014; · 4.13 Impact Factor
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    ABSTRACT: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated 141 patients who were planned to receive acyclovir at 200mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 11/2013; · 2.17 Impact Factor
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    ABSTRACT: Severe adverse events (SAE) and late hematological malignancies have been reported after PBSC donation. No prospective data on incidence and risk factors have been available for family donors so far. The Japan Society for Hematopoietic Cell Transplantation (JSHCT) introduced therefore in 2000 a mandatory registration system. It defined standards for donor eligibility and asked harvest centers to report any SAE immediately. All donors were examined at day 30 and were to be contacted once each year for a period of 5 years. Acute SAEs within day 30 were reported from 47/3264 donations (1.44%) with 14 events considered as unexpected and severe (0.58%). No donor died within 30 days. Late SAEs were reported from 39/1708 donors (2.3%). The incidence of acute SAEs was significantly higher among donors not matching the JSHCT standards (P=0.0023). Late hematological malignancies in PBSC donors were not different compared with a retrospective cohort of BM donors (N:1/1708 vs N:2/5921; P=0.53). In conclusion, acute and late SAEs do occur in PBSC donors at relatively low frequency but risk factors can be defined.Bone Marrow Transplantation advance online publication, 30 September 2013; doi:10.1038/bmt.2013.147.
    Bone marrow transplantation 09/2013; · 3.00 Impact Factor
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    ABSTRACT: Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.
    Clinical Transplantation 08/2013; · 1.63 Impact Factor
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    ABSTRACT: Cellular immunity is important for the control of CMV infection after allogeneic hematopoietic cell transplantation (Allo-HCT). However, the actual in vivo dynamics of CMV-specific cytotoxic T cell (CMV-CTL) clones are still unclear. We conducted clone monitoring of tetramer(+) CMV-CTLs in HLA-A*2402-positive donor-patient pairs, using a direct single-cell analysis that enabled the simultaneous identification and quantification of CTL clones. Clone dynamics were assessed in three cases with or without CMV reactivation. In Case-1 without CMV reactivation, despite the long-term use of systemic steroid, dominant clones of Donor-1 persisted and remained dominant. The CMV-CTLs at 1 year after Allo-HCT included a high proportion of CD45RA(+)CCR7(-) effector and CD27(-)CD57(+)mature T cells. On the other hand, in Cases-2 and -3 with CMV reactivation, novel clones appeared and became dominant during the follow-up. Their CMV-CTLs included more CD27(+) immature T cells at 1 year after Allo-HCT. With regard to clonotypes, HLA-A*2402-restricted CMV-CTLs tended to select BV7 and BJ1-1 genes for complementarity-determining region 3 (CDR3) of T-cell receptor (TCR)-β. Specific amino-acid sequences of CDR3 of TCR-β were found in each case. Patterns of clone reconstitution and phenotype would be different according to CMV reactivation. In vivo clone monitoring of CMV-CTLs could provide insight into the mechanism of immunological reconstitution following Allo-HCT.Bone Marrow Transplantation advance online publication, 12 August 2013; doi:10.1038/bmt.2013.122.
    Bone marrow transplantation 08/2013; · 3.00 Impact Factor

Publication Stats

4k Citations
1,184.92 Total Impact Points


  • 2014
    • Saitama Medical University
      • Department of Hematology and Oncology
      Saitama, Saitama, Japan
  • 2008–2014
    • Jichi Medical University
      • Division of Hematology
      Totigi, Tochigi, Japan
  • 2013
    • Tokyo Women's Medical University
      Edo, Tōkyō, Japan
  • 2004–2012
    • Keio University
      • School of Medicine
      Tokyo, Tokyo-to, Japan
  • 2011
    • Chiba Kaihin Municipal Hospital
      Tiba, Chiba, Japan
    • Chiba University
      • Department of Hematology
      Chiba-shi, Chiba-ken, Japan
    • Cincinnati Children's Hospital Medical Center
      Cincinnati, Ohio, United States
    • Tokyo Metropolitan Ohtsuka Hospital
      Edo, Tōkyō, Japan
  • 2001–2011
    • National Cancer Center, Japan
      • Endoscopy Division
      Edo, Tōkyō, Japan
  • 2000–2011
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
    • National Institute for Basic Biology
      Okazaki, Aichi, Japan
  • 2010
    • Kurume University
      Куруме, Fukuoka, Japan
  • 1995–2010
    • The University of Tokyo
      • • Department of Hematology and Oncology
      • • Department of Internal Medicine
      • • Faculty & Graduate School of Medicine
      • • Department of Cell Therapy and Transplantation Medicine
      • • Division of Internal Medicine
      Edo, Tōkyō, Japan
  • 2000–2009
    • Toranomon Hospital
      Edo, Tōkyō, Japan
  • 2000–2008
    • Tokyo Medical University
      • • Division of Hematology
      • • Division of Radiology
      Edo, Tōkyō, Japan
  • 2007
    • Yokohama City University
      • Department of Hematology
      Yokohama, Kanagawa, Japan
    • University of Michigan
      • Division of Hematology and Oncology
      Ann Arbor, MI, United States
  • 1999–2007
    • High Energy Accelerator Research Organization
      • Radiation Science Research Center
      Tsukuba, Ibaraki, Japan
  • 2005
    • Kyushu University
      • Division of Internal Medicine
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2001–2003
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 1996–2002
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan