Mitsuru Tsudo

Osaka Red Cross Hospital, Ōsaka, Ōsaka, Japan

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Publications (109)372.55 Total impact

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    ABSTRACT: Multicentric Castleman's disease is a systemic inflammatory disorder characterized by lymphadenopathy and excessive interleukin-6 production. A unique clinicopathologic variant of multicentric Castleman's disease, TAFRO (i.e., thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly) syndrome, was recently proposed in Japan. Despite the successful use of anti-interleukin-6 therapy in some patients with TAFRO syndrome, not all patients achieve remission. The pathophysiological etiology of and suitable therapeutic strategies for this variant have not been established. Here, we present our experience of a unique case of TAFRO syndrome in a 78-year-old woman whose symptoms responded differently to several therapies. Tocilizumab, an anti-interleukin-6 receptor antibody, successfully induced remission of fever and lymphadenopathy. However, severe thrombocytopenia persisted and she developed anasarca, ascites, and pleural effusion shortly thereafter. Rituximab, an anti-CD20 antibody, and glucocorticoid therapy provided no symptom relief. In contrast, cyclosporine A, an immunosuppressive agent that blocks T cell function by inhibiting interleukin-2, yielded immediate improvements in systemic fluid retention and a gradual increase in platelet count, with complete resolution of disease symptoms. Excessive serum interleukin-2, when used as an anti-cancer agent, has been reported to cause side effects such as fluid retention, thrombocytopenia, and renal failure. Our case was unique because the anti-interleukin-2 therapy successfully improved symptoms that were not relieved with anti-interleukin-6 therapy. The present report therefore provides insight into the possible role of interleukin-2, in addition to interleukin-6, in TAFRO syndrome. This report will certainly help to clarify the pathogenesis of and optimal treatment strategies for TAFRO syndrome.
    Full-text · Article · Aug 2015 · The Tohoku Journal of Experimental Medicine
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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.
    No preview · Article · Apr 2015 · American Journal of Hematology
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    Goichi Tatsumi · Naoya Ukyo · Hirokazu Hirata · Mitsuru Tsudo
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    ABSTRACT: Primary hepatic lymphoma (PHL) has rarely been reported in patients with immunosuppression. We herein describe a case of Epstein-Barr virus- (EBV-) positive PHL in a 67-year-old Japanese woman receiving methotrexate (MTX) treatment for rheumatoid arthritis (RA). The patient, who had been receiving MTX therapy for more than 6 years, presented with low-grade fever and abdominal pain. Initial laboratory tests showed mildly elevated liver enzymes with normal levels of alpha-fetoprotein and carcinoembryonic antigen, and computed tomography scans revealed multiple hepatic tumors with no lymph-node swelling. Examination of liver specimens obtained via ultrasonography-guided needle biopsy indicated EBV-positive diffuse large B cell lymphoma; therefore, she was diagnosed with PHL. MTX was discontinued, and she was carefully monitored thereafter owing to the prolonged history of MTX administration for RA. Rapid progression of PHL was observed; therefore 10 days after the PHL diagnosis, she received 6 cycles of R-THP-COP (rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone) therapy and achieved complete remission for more than 1 year. Although MTX-associated lymphoproliferative disorders often show remission after withdrawal of MTX, early diagnosis and treatment are essential for PHL in patients with RA treated with MTX, because of the aggressive nature of the disease.
    Full-text · Article · Dec 2014
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    ABSTRACT: We retrospectively investigated the prognostic factor of lenalidomide plus low-dose dexamethasone (Rd) in Japanese patients with refractory or relapsed multiple myeloma (RRMM) registered in the Kansai Myeloma Forum from January 2006 to December 2013. A total of 140 patients were analyzed. The median age was 66 years. The overall response rate was 68.6 %, including 33.1 % with a better than very good partial response. At 13.0 months median follow-up, the median overall survival (OS) and progression-free survival (PFS) were 34.2 and 17.0 months, respectively. In univariate analyses, patients with one or two prior therapies had significantly longer OS (41.2 vs. 21.5 months; P = 0.002) and PFS (29.0 vs. 13.0 months; P = 0.006) than patients treated with three or more prior therapies. Prior use of thalidomide was associated with significantly shorter PFS (19.0 vs. 16.0 months; P = 0.045). The prior use of bortezomib or high-dose therapy with stem cell transplantation, and the International Staging System had no impact on long-term outcome. Multivariate analysis showed that only the number of prior therapies was a significant predictor of both OS and PFS. Our findings suggest that greater benefit may occur when Rd therapy is used at the first or second relapse in RRMM.
    Full-text · Article · Nov 2014 · International Journal of Hematology
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    ABSTRACT: The patient was a 70-year-old woman with lymphoplasmacytic lymphoma which showed a predominantly diffuse involvement of the bone marrow and kidney. Because atypical lymphocytes appeared in the cerebrospinal fluid, the intrathecal administration of methotrexate (MTX) and cytosine arabinoside (Ara-C) was repeated several times. The patient developed flaccid paraplegia 8 months after the beginning of intrathecal administration, and died 4 months later. Autopsy demonstrated extensive transverse necrosis involving the lower thoracic cord and marked vacuolar degeneration of the white matter of the cervical, upper thoracic and lumbo-sacral cord. Focal vacuolar degeneration of the white matter was also noted in the left parietal lobe. Although vacuolar degeneration of the white matter is a common feature in MTX myelopathy, extensive transverse necrosis is rare. In the present case, an overlapping of two mechanisms, that is, injury of vascular endothelial cells and the direct toxic effect of MTX and Ara-C on the white matter, probably played a crucial role in the pathogenesis of severe myelopathy. Because severe myelopathy occurs infrequently, considering the large number of patients receiving the intrathecal administration of MTX, it is possible that a constitutional predisposition or abnormal sensitivity to MTX was involved in the pathogenesis in the present patient.
    No preview · Article · Jul 2014 · Neuropathology
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    ABSTRACT: We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents.
    Full-text · Article · Apr 2014 · International Journal of Hematology
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    ABSTRACT: We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents.
    No preview · Article · Mar 2014 · International Journal of Hematology
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    ABSTRACT: Fibrosing mediastinitis is rare. One type of this disease is idiopathic fibrosing mediastinitis. It is necessary to rule out malignancy in order to accurately diagnose fibrosing mediastinitis. We herein report a case of anaplastic large cell lymphoma diagnosed three months after a preliminary diagnosis of fibrosing mediastinitis. Glucocorticoid therapy was not successful in controlling disease progression. Immediately after initiating chemotherapy for lymphoma, the patient's symptoms improved dramatically and the mediastinal lesion decreased in size. Although few similar cases have been reported, hidden malignancy may present as fibrosing mediastinitis. Therefore, physicians should consider the probability of malignancy in patients with fibrosing mediastinitis because treatments may vary accordingly.
    No preview · Article · Dec 2013 · Internal Medicine
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT), but not autologous HCT, can provide long-term remission in some adult T-cell leukemia-lymphoma (ATL) patients. We retrospectively analyzed the effects of acute graft-versus-host disease (GVHD) among the 616 ATL patients who survived at least 30 days after allogeneic HCT other than cord blood transplantation. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that grades 1-2 acute GVHD were associated with favorable overall survival (OS) (hazard ratio, 0.634; 95% confidence interval, 0.477-0.843) while grades 3-4 acute GVHD had a trend toward unfavorable OS (1.380; 0.988-1.927) compared with non-acute GVHD. Subsequent multivariate analyses of patients who survived at least 100 days after HCT (n=431) demonstrated that the presence of limited and extensive chronic GVHD, respectively, had a trend toward (0.597; 0.354-1.007) and a significant effect on (0.585; 0.389-0.880) favorable OS. There were no significant interactions between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) with OS even when acute GVHD was absent or present at grades 1-2 or grades 3-4 or when chronic GVHD was absent, limited, or extensive. The present study demonstrated the actual existence of graft-versus-ATL effects in the ATL patients whether MAC or RIC was used.
    Full-text · Article · Sep 2013 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: Background The epidemiology of human herpesvirus 6 (HHV-6) encephalitis after allogeneic hematopoietic cell transplantation (HCT) and its relationship with HHV-6 reactivation have not been sufficiently characterized.Methods This prospective, multicenter study of 230 allogeneic HCT recipients investigated the epidemiology of HHV-6 reactivation and HHV-6 encephalitis. Plasma HHV-6 DNA load was prospectively evaluated twice weekly until 70 days after HCT.ResultsCumulative incidence of positive HHV-6 DNA and high-level HHV-6 reactivation (plasma HHV-6 DNA ≥104 copies/mL) at day 70 after HCT was 72.2% and 37.0%, respectively. Multivariate analysis identified myeloablative conditioning (hazard ratio [HR], 1.9; P =. 004), umbilical cord blood transplantation (UCBT) (HR, 2.0; P =. 003), and male sex (HR, 1.6; P =. 04) as risk factors for displaying high-level HHV-6 reactivation. HHV-6 encephalitis occurred in 7 patients, and cumulative incidence at day 70 was 3.0%. None of the144 patients without high-level HHV-6 reactivation and 7 of 86 patients (8.1%) with high-level HHV-6 reactivation developed HHV-6 encephalitis (P =. 0009). Prevalence of HHV-6 encephalitis was significantly higher among patients receiving UCBT than in patients with other sources (cumulative incidence at day 70, 7.9% vs 1.2%, P =. 008). In each of 7 patients with HHV-6 encephalitis, central nervous system (CNS) symptoms developed concomitant with peak plasma HHV-6 DNA (range, 21 656-433 639 copies/mL).Conclusions High levels of plasma HHV-6 DNA are associated with higher risk of HHV-6 encephalitis. UCBT is a significant risk factor for HHV-6 encephalitis. HHV-6 encephalitis should be considered if CNS dysfunction develops concomitant to high-level plasma HHV-6 DNA after allogeneic HCT. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
    Preview · Article · May 2013 · Clinical Infectious Diseases

  • No preview · Article · Mar 2013 · Leukemia & lymphoma
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    ABSTRACT: Splenic abscess is a rare clinical condition with a high mortality rate. Multiple splenic abscesses, rather than a solitary abscess, are present in immunocompromised states including hematological malignancies. As symptoms of splenic abscesses, fever and abdominal pain, are non-specific, timely and adequate use of imaging studies is crucial for early diagnosis. We report the cases of 2 patients with myelodysplastic syndrome and multiple splenic abscesses. Notwithstanding the higher mortality rate of patients with multiple splenic abscesses as compared with those with a solitary splenic abscess, we successfully treated the 2 patients by using antibiotic therapy and fine needle aspiration.
    Full-text · Article · Jun 2012 · Internal Medicine
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    Hiroki Nishikawa · Mitsuru Tsudo · Yukio Osaki
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    ABSTRACT: Clinical outcome of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis C virus (HCV) infection in the rituximab era remains unclear. The aim of the present study was to compare the clinical outcome, treatment response and hepatotoxicity in DLBCL patients who received rituximab containing immunochemotherapy that had HCV infection and those that did not have HCV infection between January 2004 and October 2011. Of the 272 consecutive histopathologically diagnosed DLBCL patients in our department, a total of 248 were retrospectively analyzed in the present study. There were 28 DLBCL patients with HCV infection (the HCV group) and 220 DLBCL patients without HCV infection (the control group). We compared overall survival (OS), progression-free survival (PFS), treatment response and hepatotoxicity according to HCV infection. In terms of OS (P=0.525) and PFS (P=0.759), there were no significant differences between the HCV group and the control group. Objective response rates were 92.9% (26/28) in the HCV group and 95.9% (211/220) in the control group (P=0.619). In the HCV group, seven patients (25.0%) developed hepatotoxicity during immunochemotherapy. In the control group, 35 patients (15.9%) developed hepatotoxicity during chemotherapy. No patient required discontinuation of immunochemotherapy owing to hepatotoxicity in either group. In terms of hepatotoxicity, there was no significant difference between these two groups (P=0.281). In conclusion, our study results suggested that HCV infection might not influence the clinical course in DLBCL patients who receive rituximab-containing immunochemotherapy.
    Preview · Article · Jun 2012 · Oncology Reports
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    ABSTRACT: To evaluate the role of tumour-associated macrophages (TAMs) of the M1 and M2 types in the behaviour of diffuse large B-cell lymphoma (DLBCL). Double immunohistochemical staining of HLA-DR/CD68 (M1) or CD163/CD68 (M2) was performed in 101 cases of DLBCL. CD68+ cells represent the total number of TAMs. The average number of double-positive cells was counted, and the cut-off value was set at the mean number of counts, i.e. 30.7 and 27.0 for M1 TAMs and M2 TAMs, respectively. That for total TAMs was set at the 90th percentile number of total counts, i.e. 132.3. Cases were categorized into three pairs: high (34 cases) and low (67 cases) M1 TAM groups, high (39 cases) and low (62 cases) M2 TAM groups, and high (10 cases) and low (91 cases) total TAM groups. The difference in overall survival rates was statistically significant between the high and low M2 TAM groups (P < 0.01) and between the high and low total TAM groups (P < 0.05). Multivariate analysis revealed that the presence of a bulky mass and a higher number of M2 TAMs were significant factors for poor prognosis (P < 0.05). Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.
    No preview · Article · Jan 2012 · Histopathology
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    ABSTRACT: Lenalidomide is known to be effective in myelodysplastic syndromes (MDS) with del(5q) in improving anemia and suppressing del(5q) cells. MDS with del(5q) shows increase of nonlobulated megakaryocytes. However, histopathology of MDS with del(5q) treated with lenalidomide has not been fully studied. We investigated the morphologic changes in lenalidomide treated low- or intermediate-1-risk MDS with del(5q). All of evaluable patients showed high proportion of nonlobulated megakaryocytes. The nonlobulated megakaryocytes were markedly decreased in 6 patients during therapy in parallel with suppression of del(5q) cells. Our analysis suggests that single allele deletion of common deleted region inhibits nuclear lobulation of megakaryocytes.
    No preview · Article · Dec 2011 · Leukemia research
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    ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells only within the lumina of small vessels in various organs. IVLBCL is an intractable hematological disease, in particular, the high incidence of central nervous system (CNS) involvement is one of the causes of the poor prognosis of IVLBCL. Autologous stem cell transplantation (ASCT) is an effective therapeutic option for refractory or high-risk aggressive lymphoma. However, it is unknown whether ASCT is an effective treatment for CNS involvement of aggressive lymphoma including IVLBCL. We show a case of a 39-year-old woman with recurrent CNS involvement of IVLBCL receiving autologous peripheral blood stem cell transplantation (auto-PBSCT) preconditioned with high-dose thiotepa, busulfan, cyclophosphamide (TBC regimen). Culture-negative febrile neutropenia developed requiring antimicrobial therapy, but nonhematological adverse effects including stomatitis and neurotoxicity, with grade ≥ 3, were not observed. The patient achieved and has maintained complete remission (CR) for 24 months after TBC/auto-PBSCT and has survived for around 30 months from the diagnosis of the CNS recurrence. The clinical course of this case suggests that auto-PBSCT preconditioned with TBC could be one of the therapeutic options for the treatment of CNS involvement of IVLBCL.
    No preview · Article · Dec 2011 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: To evaluate roles of tumor-associated macrophages (TAMs) for prognosis of classical Hodgkin lymphoma (CHL). Expression of markers for TAMs, CD68, HLA-DR, CD163, HLA-DR/CD68 (M1), and CD163/CD68 (M2) was immunohistochemically examined in 82 cases with CHL. Positively stained cells were counted and correlation of number of TAMs and patients' survival time was analyzed. Number of CD163+ cells and M2 cells was significantly correlated with shorter overall survival (P < 0.05), while it was marginally significant for CD68+ cells (P = 0.0827). HLA-DR + cells and M1 cells showed no significant correlation with overall survival. When confined to mixed cellularity subtype, number of M1 cells was correlated with favorable prognosis (P < 0.05), while M2 did not (P = 0.7). Older age and male sex were unfavorable factors for prognosis. At multivariate analysis, number of CD163+ cells, M2+ cells, and age were independent factors for poor overall survival (P = 0.03, 0.02, and 0.01, respectively). CD163+ cells and M2 cells might work to be tumor promotive in CHL. M1 cells might be tumor suppressive in mixed cellularity type.
    No preview · Article · Aug 2011 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
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    ABSTRACT: Age-related EBV-associated B-cell lymphoproliferative disorder is a highly aggressive lymphoma, and a standard therapy for this disease has not yet been established. A 58-year-old male was admitted to our hospital because of fever and lymphadenopathy across the whole body. Neck lymph node biopsy showed hemorrhagic and geographic necrosis with Hodgkin-like large cells against a background of small lymphocytes. The large cells were positive for CD30 and EBER. The patient was diagnosed as having age-related EBV-associated B-cell lymphoproliferative disorder. Although there was no response to CHOP therapy, he obtained partial response after 3 courses of DeVIC therapy. Because his lymphoma was highly aggressive and chemotherapy-resistant, he underwent autologous stem cell transplantation with a conditioning regimen including ranimustine, etoposide, cytarabine, and melphalan. After stem cell transplantation and subsequent radiotherapy to the residual lesion, the patient achieved complete remission. This is the first report of successful autologous stem cell transplantation for a patient with age-related EBV-associated B-cell lymphoproliferative disorder.
    No preview · Article · Mar 2011 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: A 62-year-old female suffering from rheumatoid arthritis (RA) for 16 years was referred to our hospital with out of breath on slight exertion. She had been prescribed with methotrexate (MTX; 4 mg per week) and prednisolone for 10 years for the treatment of RA. Upon physical examination, tender liver and spleen that extended below the xiphoid were palpable with a protuberant abdomen. Computed tomography (CT) showed hepatosplenomegaly, bilateral pleural effusions and ascites in the absence of lung field abnormalities or lymphadenopathy. Bone marrow examination was performed to demonstrate an infiltration of clonal B cells confirmed by immunocytological analysis with flow cytometry. She was diagnosed as having MTXassociated lymphoproliferative disorder (LPD). The effusions in the body cavities and hepatosplenomegaly were dramatically improved only with the withdrawal of MTX. She had been asymptomatic for 2 years until the current hospitalization. She presented herself in the outpatient department with a complaint of headache, vertigo and loss of vision and then she was readmitted because of extensive fluid retention in the chest, abdomen and lower extremities. A CT scan showed recurrence of the massive effusions in the body cavities and hepatosplenomegaly (Fig. 1a). Histological analysis for the liver specimen obtained by an ultrasoundguided needle biopsy showed a typical relatively monotonous appearance of lymphocytes, plasmacytoid lymphocytes
    Full-text · Article · Feb 2011 · International journal of hematology
  • E Iguchi · T Minakata · M Tsudo
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    ABSTRACT: Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
    No preview · Article · Feb 2011 · Bone marrow transplantation

Publication Stats

3k Citations
372.55 Total Impact Points

Institutions

  • 2003-2015
    • Osaka Red Cross Hospital
      Ōsaka, Ōsaka, Japan
  • 2011
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 1992-1994
    • National Institutes of Health
      • • Branch of Metabolism
      • • Laboratory of Molecular Biology
      베서스다, Maryland, United States
  • 1990-1993
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
    • University of Leuven
      Louvain, Flemish, Belgium
    • University of Wisconsin, Madison
      • Department of Human Oncology
      Madison, MS, United States
  • 1991-1992
    • Unitika
      Ōsaka, Ōsaka, Japan
    • Tokyo Metropolitan Institute
      Edo, Tokyo, Japan
  • 1988
    • National Cancer Institute (USA)
      • Metabolism Branch
      Maryland, United States
  • 1982-1987
    • Kyoto University
      Kioto, Kyōto, Japan