Yoshinobu Kanda

Jichi Medical University, Totigi, Tochigi, Japan

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Publications (325)1218.52 Total impact

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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; DOI:10.1016/j.bbmt.2015.04.012 · 3.35 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; DOI:10.1002/ajh.24028 · 3.48 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 · 4.02 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 · 3.47 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; DOI:10.1016/j.bbmt.2015.02.015 · 3.35 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 · 1.68 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S159-S160. DOI:10.1016/j.bbmt.2014.11.229 · 3.35 Impact Factor
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    ABSTRACT: Adult mixed phenotype acute leukemia (MPAL) patients have a poor prognosis, and the therapeutic role of allogeneic stem cell transplantation (allo-SCT) for MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of allo-SCT for MPAL. Eighteen patients with MPAL were identified from the transplant outcome database of KSGCT. We also selected 215 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method. The 5-year overall survival (OS) rate of patients with MPAL was 48.1%, and patients in remission at the time of transplant showed significantly better survival than those not in remission (5-year OS: 71.8% vs. 0%, p = 0.001). No significant differences were seen in OS when stratifying patients according to immunophenotype, cytogenetic abnormalities, or the type of induction therapy. The 5-year OS rate of MPAL patients was not significantly different compared with AML control patients (48.1% vs. 48.1%; p = 0.855) or ALL control patients (48.1% vs. 37.8%; p = 0.426). These results suggested that allo-SCT is an effective treatment for MPAL, especially early in the disease course, and innovative transplant approaches are warranted to improve the transplant outcome of MPAL patients who are not in remission. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 01/2015; DOI:10.1111/ejh.12516 · 2.41 Impact Factor
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    ABSTRACT: Background Bloodstream infections (BSI) are frequently observed after allogeneic hematopoietic stem cell transplant (HSCT), and could cause morbidity and mortality.Methods We retrospectively evaluated the incidence, characteristics of, and risk factors for BSI at both pre- and post-engraftment in 209 adult HSCT patients at our institute between June 2006 and December 2013. The median age at transplantation was 45 years (range, 15–65). A total of 122 patients received bone marrow, 68 received peripheral blood stem cells, and 19 received umbilical cord blood.ResultsThe cumulative incidences of pre- and post-engraftment BSI were 38.9% and 17.2%, respectively. Nine patients had both pre- and post-engraftment BSI. In the pre- and post-engraftment periods, respectively, 67.4% and 84.1% of isolates were gram-positive bacteria (GPB), 28.3% and 11.4% were gram-negative bacteria (GNB), and 4.3% and 4.5% were fungi. Coagulase-negative staphylococci were the most commonly isolated GPB, while Stenotrophomonas maltophilia and Pseudomonas aeruginosa were the most commonly isolated GNB. Pre-engraftment BSI was associated with an increased risk of death. Overall survival at day 180 for patients with or without pre-engraftment BSI was 70.0% and 82.7%, respectively (P = 0.02).Conclusions Risk factors for BSI in the pre-engraftment period were the interval between diagnosis and transplantation (261 days or more), engraftment failure, and high-risk disease status at HSCT in a multivariate analysis. No significant risk factor for BSI in the post-engraftment period was identified by a univariate analysis. These findings may be useful for deciding upon empiric antibacterial treatment for HSCT recipients.
    Transplant Infectious Disease 01/2015; 17(1). DOI:10.1111/tid.12345 · 1.98 Impact Factor
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    ABSTRACT: We compared the expected medical costs of empirical and preemptive treatment strategies for invasive fungal infection in neutropenic patients with hematological diseases. Based on the results of two clinical trials with different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350-355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051; PREVERT study], we developed a decision tree model that represented the outcomes of empirical and preemptive treatment strategies, and estimated the expected medical costs of medications and examinations in the two strategies. We assumed that micafungin was started in the empirical group at 5 days after fever had developed, while voriconazole was started in the preemptive group only when certain criteria, such as positive test results of imaging studies and/or serum markers, were fulfilled. When we used an incidence of positive test results of 6.7 % based on the Oshima study, the expected medical costs of the empirical and preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of the PREVERT study, in which the incidence of positive test results was 32.9 %, the expected medical costs in the empirical and preemptive groups were 291,871 and 284,944 yen, respectively. A sensitivity analysis indicated that the expected medical costs in the preemptive group would exceed those in the empirical group when the incidence of positive test results in the former was over 34.4 %. These results suggest that a preemptive treatment strategy can be expected to reduce medical costs compared with empirical therapy in most clinical settings.
    European Journal of Clinical Microbiology 01/2015; 34(5). DOI:10.1007/s10096-014-2311-8 · 2.54 Impact Factor
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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 12/2014; 4:e263. DOI:10.1038/bcj.2014.85 · 2.88 Impact Factor
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    ABSTRACT: Objectives Limited data are available on the effect of how cyclophosphamide (CY) and total body irradiation (TBI) are administered. We analyzed the effect of the interval from TBI to hematopoietic stem cell transplantation (HSCT) on the outcome of HSCT. Methods Adult patients who underwent HSCT using myeloablative conditioning consisting of TBI and CY were retrospectively analyzed. They were divided into three groups according to the duration between the start of TBI and HSCT (Group A: 2-4 days, Group B: 5-8 days, Group C: 9-10 days). Results Seventy-five adult patients were included. The 3-year overall survival rate was 56, 47, and 77% in Groups A, B, and C, respectively (P = 0.14). Similarly, there was no significant difference among the three groups with respect to progression-free survival (57, 47, and 72%, P = 0.17), relapse rate (32, 37, and 16%, P = 0.29), or non-relapse mortality (8, 14, and 12%, P = 0.81). In addition, we observed no significant difference among the three groups with respect to the incidence of grade II-IV acute graft-versus-host disease (GVHD) (31, 47, and 32%, respectively, P = 0.56) and that of chronic GVHD (23, 23, and 22%, respectively, P = 0.97). Discussion and conclusion Although recipient immune system at HSCT might be affected by the timing of TBI, the duration between the start of TBI and HSCT did not influence the outcome of HSCT using myeloablative conditioning with TBI and CY.
    Hematology (Amsterdam, Netherlands) 12/2014; DOI:10.1179/1607845414Y.0000000217 · 1.19 Impact Factor
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    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; DOI:10.1111/tid.12318 · 1.98 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 11/2014; 20(11). DOI:10.1016/j.bbmt.2014.07.010 · 3.35 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; 27(2):1973947814Y0000000219. DOI:10.1179/1973947814Y.0000000219 · 1.07 Impact Factor
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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 10/2014; DOI:10.1016/j.bbmt.2014.06.005 · 3.35 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; DOI:10.1111/tid.12304 · 1.98 Impact Factor
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    ABSTRACT: Recently, elevated peripheral blood monocyte counts at diagnosis have been shown to be an independent marker associated with poor prognosis in patients with both non-Hodgkin and Hodgkin lymphoma. In this study, we retrospectively analyzed the data from a total of 550 patients with diffuse large B-cell lymphoma and evaluated the relationship between central nervous system relapse and the absolute monocyte counts at diagnosis. Twenty-six patients developed central nervous system relapse. The central nervous system relapse-free survival was significantly lower in patients with the absolute monocyte counts ≥0.51 109/L (87.8% vs. 96.4%, P<0.001). It was independently significant after adjusting for other significant factors, including systemic relapse as a time-dependent covariate by multivariate analysis (hazard ratio 2.46, 95% confidence intervals 1.05-5.75, P=0.039). These results suggested the absolute monocyte counts at diagnosis is an independent significant risk factor for central nervous system relapse in patients with diffuse large B-cell lymphoma.
    Haematologica 09/2014; DOI:10.3324/haematol.2014.114934 · 5.87 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; DOI:10.1007/s12185-014-1650-7 · 1.68 Impact Factor
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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; 49(9). DOI:10.1038/bmt.2014.141 · 3.47 Impact Factor

Publication Stats

5k Citations
1,218.52 Total Impact Points

Institutions

  • 2008–2015
    • Jichi Medical University
      • Division of Hematology
      Totigi, Tochigi, Japan
  • 2014
    • Saitama Medical University
      • Department of Hematology and Oncology
      Saitama, Saitama, Japan
  • 2012
    • Duke University Medical Center
      • Division of Cellular Therapy
      Durham, North Carolina, United States
  • 2011
    • Tokyo Metropolitan Ohtsuka Hospital
      Edo, Tōkyō, 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
  • 2000–2009
    • Toranomon Hospital
      Edo, Tōkyō, Japan
    • National Institute for Basic Biology
      Okazaki, Aichi, Japan
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 2000–2008
    • Tokyo Medical University
      • Division of Hematology
      Edo, Tōkyō, 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
  • 2005
    • Dokkyo University
      Edo, Tōkyō, Japan
  • 2004
    • Nagasaki University
      Nagasaki, Nagasaki, Japan
  • 2003
    • Keio University
      Edo, Tōkyō, Japan
    • Kagoshima University
      • Department of Pediatrics
      Kagosima, Kagoshima, Japan
  • 2002–2003
    • National Cancer Center, Japan
      • Endoscopy Division
      Edo, Tōkyō, Japan
  • 1999–2001
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan