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Tetsuya Eto,
Ken Takase,
Toshihiro Miyamoto,
Yuju Ohno,
Tomohiko Kamimura,
Koji Nagafuji,
Yasushi Takamatsu,
Takanori Teshima,
Hisashi Gondo,
Shuichi Taniguchi,
Koichi Akashi, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: We retrospectively analyzed the outcomes of 81 patients with non-M3 acute myelogenous leukemia (AML) in first complete remission (CR1) who were treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (Auto-PBSCT) by the Fukuoka Blood and Marrow Transplantation Group between 1989 and 2005. Cytogenetically, 16 patients were defined as good risk, 56 as intermediate risk, and nine as poor risk, following the Southwest Oncology Group criteria. The pre-transplant conditioning regimen consisted of high-dose busulfan, etoposide, and cytarabine (BEA regimen), combined with priming by granulocyte colony-stimulating factor (G-CSF). Disease-free survival (DFS) and overall survival at 5 years were 64.0 % (95 % CI 52.5-73.4) and 66.4 % (95 % CI 54.9-75.6) after Auto-PBSCT at a median follow-up time of 103 months (range 3-240 months), respectively. Two patients died of transplant-related pulmonary complications 6 months after Auto-PBSCT without relapse. The 5-year DFS rates of patients in the genetically good-, intermediate-, and poor-risk groups were 80.8, 64.3, and 33.3 %, respectively, but there was no significant difference statistically among the risk groups (log-rank p = 0.0579). These observations suggest that HDCT supported by Auto-PBSCT with the BEA regimen combined with G-CSF priming is a therapeutic option for postremission therapy of AML in CR1.
International journal of hematology 06/2013; · 1.17 Impact Factor
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Koji Nagafuji,
Toshihiro Miyamoto,
Tetsuya Eto,
Tomohiko Kamimura,
Shuichi Taniguchi,
Takashi Okamura,
Eiichi Ohtsuka,
Takashi Yoshida,
Masakazu Higuchi,
Goichi Yoshimoto,
Tomoaki Fujisaki,
Yasunobu Abe,
Yasushi Takamatsu,
Shouhei Yokota,
Koichi Akashi, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) for patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is much more intensive than multi-agent combined chemotherapy, although allogeneic HSCT is associated with increased morbidity and mortality when compared with such chemotherapy. Minimal residual disease (MRD) status has been proven to be a strong prognostic factor for adult patients with Ph-negative ALL. METHODS: We investigated whether MRD status in adult patients with ALL is useful to decide clinical indications for allogeneic HSCT. We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL. RESULTS: Of 110 adult ALL patients enrolled between July 2002 and August 2008, 101 were eligible, including 59 Ph-negative patients. MRD status was assessed in 43 patients by the detection of major rearrangements in TCR and Ig and the presence of chimeric mRNA. Thirty-nine patients achieved CR1, and their probabilities of 3-year overall survival and disease-free survival (DFS) were 74% and 56%, respectively. Patients who were MRD-negative after induction therapy (n = 26) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 13; 69% vs. 31%, p = 0.004). All of 3 patients who were MRD-positive following consolidation chemotherapy and did not undergo allogeneic HSCT, relapsed and died within 3 years after CR. CONCLUSIONS: These results indicate that MRD monitoring is useful for determining the clinical indications for allogeneic HSCT in the treatment of ALL in CR1.
Journal of Hematology & Oncology 02/2013; 6(1):14. · 3.99 Impact Factor
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Mitsuhiro Fukata,
Fumihiko Ishikawa,
Yuho Najima,
Takuji Yamauchi,
Yoriko Saito,
Katsuto Takenaka,
Kohta Miyawaki,
Hideki Shimazu,
Kazuya Shimoda,
Takaaki Kanemaru,
Kei-Ichiro Nakamura,
Keita Odashiro,
Koji Nagafuji, Mine Harada,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Definite identification of the cell types and the mechanism relevant to cardiomyogenesis is essential for effective cardiac regenerative medicine. We aimed to identify the cell populations that can generate cardiomyocytes and to clarify whether generation of donor-marker(+) cardiomyocytes requires cell fusion between BM-derived cells and recipient cardiomyocytes. METHODOLOGYPRINCIPAL FINDINGS: Purified BM stem/progenitor cells from green fluorescence protein (GFP) mice were transplanted into C57BL/6 mice or cyan fluorescence protein (CFP)-transgenic mice. Purified human hematopoietic stem cells (HSCs) from cord blood were transplanted into immune-compromised NOD/SCID/IL2rγ(null) mice. GFP(+) cells in the cardiac tissue were analyzed for the antigenecity of a cardiomyocyte by confocal microscopy following immunofluorescence staining. GFP(+) donor-derived cells, GFP(+)CFP(+) fused cells, and CFP(+) recipient-derived cells were distinguished by linear unmixing analysis. Hearts of xenogeneic recipients were evaluated for the expression of human cardiomyocyte genes by real-time quantitative polymerase chain reaction. In C57BL/6 recipients, Lin(-/low)CD45(+) hematopoietic cells generated greater number of GFP(+) cardiomyocytes than Lin(-/low)CD45(-) mesenchymal cells (37.0+/-23.9 vs 0.00+/-0.00 GFP(+) cardiomyocytes per a recipient, P = 0.0095). The number of transplanted purified HSCs (Lin(-/low)Sca-1(+) or Lin(-)Sca-1(+)c-Kit(+) or CD34(-)Lin(-)Sca-1(+)c-Kit(+)) showed correlation to the number of GFP(+) cardiomyocytes (P<0.05 in each cell fraction), and the incidence of GFP(+) cardiomyocytes per injected cell dose was greatest in CD34(-)Lin(-)Sca-1(+)c-Kit(+) recipients. Of the hematopoietic progenitors, total myeloid progenitors generated greater number of GFP(+) cardiomyocytes than common lymphoid progenitors (12.8+/-10.7 vs 0.67+/-1.00 GFP(+) cardiomyocytes per a recipient, P = 0.0021). In CFP recipients, all GFP(+) cardiomyocytes examined coexpressed CFP. Human troponin C and myosin heavy chain 6 transcripts were detected in the cardiac tissue of some of the xenogeneic recipients. CONCLUSIONSSIGNIFICANCE: Our results indicate that HSCs resulted in the generation of cardiomyocytes via myeloid intermediates by fusion-dependent mechanism. The use of myeloid derivatives as donor cells could potentially allow more effective cell-based therapy for cardiac repair.
PLoS ONE 01/2013; 8(5):e62506. · 4.09 Impact Factor
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Hiromitsu Daisaki,
Ukihide Tateishi,
Takashi Terauchi,
Mitsuaki Tatsumi,
Kazufumi Suzuki,
Naoki Shimada,
Hiroyuki Nishida,
Akihiko Numata,
Koji Kato,
Koichi Akashi, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: A multicenter trial is currently underway using FDG-PET/CT to evaluate diffuse large B cell lymphoma in Japan (JSCT NHL10). Standardization of the image quality between the participating centers is a fundamental aspect of the study. Within the framework of JSCT NHL10, standardization of the image quality was attempted by optimizing the acquisition and reconstruction conditions using mid-therapy FDG-PET/CT for diffuse large B cell lymphoma. This report describes the procedures and results of this attempt. METHODS: The acquisition protocols and imaging quality were initially determined at each center and again after modification. The image quality was based on performance with an (18)F-filled National Electrical Manufacturers Association standards body phantom. We determined that the acquisition duration and reconstruction parameters of each scanner evaluated were in compliance with the Japanese guideline for the oncology FDG-PET/CT data acquisition protocol: synopsis of Version 1.0 (the Guideline) based on the results of the phantom experiments performed by the Core Laboratory. RESULTS: A total of 18 centers (19 scanners) participated in this trial. The center's default protocol was unchanged for 9 scanners (47.4 %) and changed for 10 scanners (52.6 %). Both acquisition duration and reconstruction parameters were changed in 3 (15.8 %) of 10 scanners and the acquisition duration alone was changed in 7 (36.8 %) scanners. Also, the accuracy of the standardized uptake value (SUV) was evaluated with the acceptable level 1.0 ± 0.1, resulting in readjustment and recalibration in 2 scanners (10.5 %), which were confirmed to attain the acceptable accuracy after the required readjustment. As of August 2012, 21 patients have undergone an FDG-PET/CT examination under the acquisition protocols determined by the Core Laboratory. Evaluation of the image quality using several physical parameters confirmed that the accumulated data were of sufficient quality. CONCLUSIONS: Optimization of the acquisition protocol, in compliance with the guideline, was successfully achieved by the Core Laboratory in the framework of JSCT NHL10 to accumulate equivalent quality data across multiple centers. The progress of the trial was greatly facilitated by support from the Japan Society of Nuclear Medicine Working Group for Investigation of Response Evaluation Criteria in Malignant Tumors Using Standardized PET/CT (Principal Investigator: Ukihide Tateishi, MD., PhD).
Annals of Nuclear Medicine 12/2012; · 1.50 Impact Factor
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Makio Furukawa,
Chikako Kiyohara,
Takahiko Horiuchi,
Hiroshi Tsukamoto,
Hiroki Mitoma,
Yasutaka Kimoto,
Ayumi Uchino,
Misato Nakagawa,
Kensuke Oryoji,
Terufumi Shimoda, Mine Harada,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: We examined the prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus (SLE). METHODS: We performed lateral radiographs of the thoracic and lumbar spine and bone mineral density (BMD) measurements and collected demographic, lifestyle, clinical, and treatment characteristics of 52 SLE patients. Vertebral fractures were defined as a >20 % reduction of vertebral body height. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were computed to assess the strength of associations between vertebral fractures and selected factors among SLE patients. RESULTS: At least one vertebral fracture was detected in 50 % of SLE patients. A history of previous bone fracture was significantly associated with an increased risk of vertebral fractures among SLE patients (adjusted OR = 14.8, 95 % CI = 1.62-134; P = 0.017). Daily use of tea or coffee was marginally associated with a decreased risk of vertebral fractures among SLE patients (adjusted OR = 0.11, 95 % CI = 0.01-1.01; P = 0.051). CONCLUSION: The high prevalence of vertebral fracture in SLE patients (50 %) indicates that we need to assess the lateral spine radiograph in more female Japanese SLE patients regardless of BMD and use of corticosteroids, although additional studies are warranted to confirm the findings suggested in this study.
Modern Rheumatology 08/2012; · 1.58 Impact Factor
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[show abstract]
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ABSTRACT: In order to study human acute B-lymphoblastic leukemia (B-ALL) in vivo, a novel xenotransplant model was established by using neonatal NOD/SCID/IL2 receptor γ chain(null) mouse. The CD34(+)CD19(+) bone marrow (BM) cells were sorted from the CD3(-)CD4(-)CD8(-) fraction of B-ALL patients by fluorescence-activated cell sorting (FACS), and injected into 100 cGy irradiated neonatal NOD/SCID/IL2rγ(null) mice through facial vein. The engraftment and proliferation of human B-ALL cells were monitored by the presence of human CD45(+)CD19(+) cells in peripheral blood (PB). Human hematopoietic chimerism in PB, BM and spleen of the recipients was examined by multiparameter flow cytometry. Morphological analyses of FACS-sorted murine marrow cells were performed by using May-Grunwald-Giemsa staining. Furthermore, leukemia cell infiltration in the organs was evaluated by hematoxylin-eosin staining. The results indicated that the sorted CD34(+)CD19(+) cells were able to initiate human B-ALL in vivo. The percentages of human CD45(+)CD19(+) cells in PB, BM and spleen of the recipient mice were (83.36 ± 10.05)%, (93.88 ± 5.05)% and (88.31 ± 5.01)%, respectively. Furthermore, the phenotype and morphology of the engrafted human cells were resemble to the original B-ALL cells from the patients. Similar to the clinical features, transplanted leukemic cells infiltrated into the organs, such as liver, lung, kidney and brain in the recipients. It is concluded that neonatal NOD/SCID/IL2rγ(null) mice can support efficient engraftment of the sorted CD34(+)CD19(+) cells from human B-ALL for a long-term period. Human-mouse xenotransplant model using neonatal NOD/SCID/IL2rγ(null) mouse may provide an important system to study the biology of human B-ALL in vivo.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 06/2012; 20(3):762-8.
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Toshio Noguchi,
Kazuma Ikeda,
Kazuhiko Yamamoto,
Atsuko Ashiba,
Isao Yoshida,
Mitsuru Munemasa,
Katsuto Takenaka,
Katsuji Shinagawa,
Fumihiko Ishimaru,
Tadashi Yoshino,
Kenji Niiya, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: Bleeding is reportedly one of the major causes of death in patients with chronic neutrophilic leukemia (CNL), but thrombocytopenia,
abnormal platelet functions, or coagulopathy has been confirmed to be the cause of the bleeding tendency in only a small proportion
of the patients. We report the case of a 49-year-old woman with CNL who experienced episodes of cutaneous and recurrent multiple
cerebral hemorrhages without severe thrombocytopenia,detectable abnormal platelet functions, or coagulating dysfunction. Histological
examination of specimens obtained at autopsy showed extensive infiltration and destruction of vascular walls by leukemic cells,
which could explain her severe bleeding tendency.This study is the first to clearly show that the infiltration and destruction
of vascular walls by leukemic cells can cause fatal bleeding episodes without warning from laboratory findings. Further studies
are needed to elucidate the mechanism of the infiltration and destruction of blood vessels by CNL cells and to develop effective
measures to control the growth and infiltration of CNL cells.
International Journal of Hematology 04/2012; 74(4):437-441. · 1.27 Impact Factor
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ABSTRACT: Acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia (AML), results from the arrest of the maturation of hematopoietic progenitors at the promyelocyte stage. It has been shown that APL is associated with a reciprocal chromosomal translocation, involving chromosomes 15 and 17, which fuses the gene encoding the retinoic acid receptor α (RARα) and the promyelocytic leukemia (PML) gene. The resultant PML-RARα fusion protein plays a critical role in the pathogenesis of APL. Although there are many subtypes of AML, all are typically managed using a standard chemotherapy regimen of an anthracycline plus cytarabine arabinoside (CA). Despite high rates of complete remission following standard chemotherapy, most patients relapse and long-term disease-free survival is only 30-40%. The introduction of drugs such as all-trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML-RARα fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. The purposes of the present review are to provide the latest results and future directions of clinical research into APL and to illustrate how new therapies, such as ATRA plus anthracycline-based induction and consolidation therapy, risk-adapted therapy, salvage therapy containing arsenic trioxide-based regimens, and hematopoietic stem cell transplantation, have improved the treatment outcomes for APL patients.
Cancer Science 07/2011; 102(11):1929-37. · 3.33 Impact Factor
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Hidetake Yabuuchi,
Yoshio Matsuo,
Hiroshi Tsukamoto,
Shunya Sunami,
Takeshi Kamitani,
Shuji Sakai,
Masamitsu Hatakenaka,
Koji Nagafuji,
Takahiko Horiuchi, Mine Harada,
Koichi Akashi,
Hiroshi Honda
[show abstract]
[hide abstract]
ABSTRACT: To evaluate what is useful among various parameters including CT findings, laboratory parameters (%VC, %DLco, KL-6), patients related data (age, sex, duration of disease) to discriminate between responder and non-responder in patients who received autologous peripheral blood stem cell transplantation (auto-PBSCT) for interstitial pneumonia (IP) with systemic sclerosis (SSc).
Auto-PBSCT and follow-up of at least one year by chest CT, serum KL-6, %VC, and %DLco were performed in 15 patients for IP with SSc. Analyzed CT findings included extent of ground-glass opacity (GGO), intralobular reticular opacity, number of segments that showed traction bronchiectasis, and presence of honeycombing. We regarded the therapeutic response of patients as responders when TLC or VC increase over 10% or DLco increase more than 15%, otherwise we have classified as non-responder. We applied univariate and multivariate analyses to find the significant indicators to discriminate responders from non-responders. P<0.05 was considered statistically significant.
Univariate and multivariate analyses showed that the significant parameter to discriminate responders from non-responders were pretreatment KL-6, presence of honeycombing, extent of GGO, and early change in extent of GGO. Among them, extent of GGO and early change in extent of GGO were the strongest discriminators between responders and non-responders (P=0.001, 0.001, respectively).
Several CT findings and pretreatment KL-6 may be useful to discriminate between responder and non-responder in patients who received auto-PBSCT for IP with SSc.
European journal of radiology 04/2011; 79(2):e74-9. · 2.65 Impact Factor
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Hiroshi Tsukamoto,
Koji Nagafuji,
Takahiko Horiuchi,
Hiroki Mitoma,
Hiroaki Niiro,
Yojiro Arinobu,
Yasushi Inoue,
Kentaro To,
Toshihiro Miyamoto,
Hiromi Iwasaki,
Takanori Teshima, Mine Harada,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc.
Eleven patients (three males and eight females) with SSc were enrolled. Blood mononuclear cells were harvested after mobilization treatment with CYC and G-CSF. CD34+ haematopoietic stem/progenitor cell fractions were purified and cryopreserved. Patients were transplanted with > 2 × 10(6)/kg autologous CD34+ cells after high-dose CYC (50 mg/kg for 4 days) conditioning. Immune reconstitution was evaluated serially by analysing lymphocyte subpopulations for 36 months.
Progressive improvement of skin sclerosis has been observed for 3 years in most of the patients. The serum level of anti-Scl-70, an auto-antibody specific to SSc, was progressively decreased after ASCT. Improvement of skin sclerosis was significantly associated with the change in the serum anti-Scl-70 level after ASCT at 36 months. Serum levels of KL-6 and surfactant protein D, indicators for interstitial pneumonia activity, were also significantly decreased. The number of CD8+ T cells immediately recovered within a month after ASCT, while the number of CD4+ T cells remained low for >36 months post-transplant. The majority of CD4+ cells were memory but not naïve T cells, and regulatory CD4+ T cells were not recovered. Th1/Th2 ratio was significantly increased after ASCT.
ASCT with purified CD34+ cells was effective in controlling the disease activity of SSc. Th1/Th2 ratio was significantly increased for at least 3 years after ASCT.
Rheumatology (Oxford, England) 12/2010; 50(5):944-52. · 4.24 Impact Factor
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Koji Nagafuji,
Keitaro Matsuo,
Takanori Teshima,
Shin-ichiro Mori,
Hisashi Sakamaki,
Michihiro Hidaka,
Hiroyasu Ogawa,
Yoshihisa Kodera,
Yoshinobu Kanda,
Atsuo Maruta, [......],
Tatsuo Ichinohe,
Masanobu Kasai,
Yoshifusa Takatsuka,
Kohmei Kubo,
Hiroshi Sao,
Yoshiko Atsuta,
Ritsuro Suzuki,
Takashi Yoshida,
Masahiro Tsuchida, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: We retrospectively analyzed the results of 707 adult patients who underwent myeloablative peripheral blood stem cell transplantation (PBSCT) (n = 365) and myeloablative bone marrow transplantation (BMT) (n = 342) for leukemia from HLA-identical sibling donors between 2000 and 2005 using the propensity score method. The results were obtained from the Japan Society for Hematopoietic Cell Transplantation registry. Multivariate Cox analysis showed that PBSCT was associated with lower overall survival (OS) in standard-risk patients [adjusted hazard ratio (aHR) = 1.83; 95% confidence interval (CI) 1.04-3.23; P = 0.036], but not in high-risk patients (aHR = 1.11; 95% CI 0.76-1.61; P = 0.599). Hematopoietic recovery was significantly faster after PBSCT. The risk of acquiring grade III-IV acute graft-versus-host disease (GVHD) (aHR = 2.23; P = 0.040) and extensive chronic GVHD (aHR = 1.93; P = 0.001) were significantly higher after PBSCT. PBSCT was associated with higher non-relapse mortality in standard-risk patients (aHR = 2.30; 95% CI 1.08-4.88; P = 0.030), but not in high-risk patients (aHR = 1.29; 95% CI 0.65-2.54; P = 0.468). Relapse after transplantation did not differ between PBSCT and BMT either in standard-risk group or in high-risk group (aHR = 1.17; 95% CI 0.55-2.52; P = 0.684 and aHR = 0.81; 95% CI 0.52-1.28; P = 0.370, respectively). In this retrospective analysis, OS was significantly lower after PBSCT in standard-risk patients, but not in high-risk patients. PBSCT was associated with significant risks of grade III-IV acute GVHD and extensive chronic GVHD.
International journal of hematology 06/2010; 91(5):855-64. · 1.17 Impact Factor
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Yasutaka Kimoto,
Takahiko Horiuchi,
Hiroshi Tsukamoto,
Chikako Kiyohara,
Hiroki Mitoma,
Ayumi Uchino,
Isao Furugo,
Seiji Yoshizawa,
Akira Ueda,
Shinichi Harashima,
Takuya Sawabe,
Tomoko Tahira,
Kenshi Hayashi,
Shigeru Yoshizawa,
Terufumi Shimoda,
Koichi Akashi, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: Identification of the association of killer cell immunoglobulin-like receptor (KIR) genes with SLE and accompanying infections.
Presence or absence of all 14 KIR genes was studied for association with SLE by case-control studies. A total of 417 SLE cases, 72 RA cases and 256 controls, all of Japanese descent, were enrolled.
The carrier frequency of KIR2DL5 was significantly decreased in SLE patients compared with healthy controls [39.3 vs 50.4%; odds ratio (OR) = 0.64; 95% CI 0.36, 0.92; P = 0.005). When the prevalence of severe infections was analysed in 184 SLE patients, whose medical records were available, KIR2DL5 carriers were at an increased risk of overall infection and viral infection (crude OR = 2.66; 95% CI 1.43, 4.92; P = 0.017 and crude OR = 2.31; 95% CI 1.15, 4.62; P = 0.017, respectively). After adjusting for methylprednisolone pulse and/or cyclophosphamide pulse therapy, KIR2DL5 carriers were at significantly greater risk of infectious events overall (adjusted OR = 2.45; 95% CI 1.24, 4.81; P = 0.0095). However, KIR2DL5 carriers were marginally associated with an increased risk of viral infectious events (adjusted OR = 2.03; 95% CI 0.94, 4.41; P = 0.0718).
KIR2DL5 was significantly associated with a decreased risk of SLE as well as an increased risk of infectious events overall in SLE patients. Our data suggest a further role of KIRs in the pathogenesis of autoimmune diseases and infection.
Rheumatology (Oxford, England) 04/2010; 49(7):1346-53. · 4.24 Impact Factor
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Makio Furukawa,
Chikako Kiyohara,
Hiroshi Tsukamoto,
Hiroki Mitoma,
Yasutaka Kimoto,
Ayumi Uchino,
Misato Nakagawa,
Kensuke Oryoji,
Terufumi Shimoda,
Koichi Akashi, Mine Harada,
Takahiko Horiuchi
[show abstract]
[hide abstract]
ABSTRACT: To examine the prevalence of and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in Japanese female patients with systemic lupus erythematosus (SLE). We performed BMD measurements by dual X-ray absorptiometry at the lumbar spine and the hip and collected basic and lifestyle-related, clinical and treatment characteristics among 58 SLE patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were assessed for associations between low BMD and selected factors among SLE patients. The mean BMD ± SD was 0.90 ± 0.17 g/cm(2) at the lumbar spine and 0.76 ± 0.17 g/cm(2) at the hip. The prevalence of osteopenia (2.5 SD < T score < 1 SD) was 50.0% and that of osteoporosis (T score < 2.5 SD) was 13.8% in our SLE patients. After adjustment for age and disease duration, we found the number of deliveries (OR = 5.58, 95% CI = 1.31-26.06; P = 0.02) to be a risk factor for overall low BMD (T score < 1 SD) and a maximal dosage of >50 mg/day of oral corticosteroids (OR = 0.25, 95% CI = 0.07-0.91; P = 0.035) as a preventive factor for low BMD at the lumbar spine. Reduced BMD, especially in spinal trabecular bone, was pronounced in Japanese female patients with SLE, particular in those with a history of delivery. A history of high-dose oral corticosteroids was associated with the preservation of BMD at the lumbar spine, however, further study is needed considering the limited sample size.
Rheumatology International 12/2009; 31(3):365-76. · 1.88 Impact Factor
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Kazutaka Sunami,
Katsuji Shinagawa,
Morio Sawamura,
Akira Sakai,
Yoshio Saburi,
Yutaka Imamura,
Ishikazu Mizuno,
Shigehisa Tamaki,
Tomohiko Kamimura,
Hiroyuki Tsuda,
Hisashi Gondo,
Norihiko Hino,
Chihiro Shimazaki,
Akira Miyata,
Fumihito Tajima,
Yoshinobu Takemoto,
Akiyoshi Miwa,
Takaaki Chou, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: The efficacy and safety of high-dose chemotherapy with tandem autologous peripheral blood stem cell transplantation (auto-PBSCT) were evaluated in a multicenter clinical study of patients with advanced multiple myeloma. Eligible patients (n = 40) were consecutively enrolled in the phase I/II study and received 2-4 cycles of vincristine-adriamycin-dexamethasone regimen. The responding patients underwent PBSC harvesting following high-dose cyclophosphamide and filgrastim administration. The first auto-PBSCT (n = 32) following high-dose melphalan (200 mg/m(2)) was performed within 2 months of PBSC harvesting; the second auto-PBSCT (n = 28) was scheduled 3-6 months later. Treatment-related mortality was 2.5% (n = 1) throughout the protocol. Grade 4 nonhematologic toxicity occurred in 12.5 and 14.3% of the first and second auto-PBSCT patients, respectively. All but one patient (who died) achieved hematopoietic recovery. For the 28 patients completing the second auto-PBSCT, the results were favorable with a response rate of 65% (complete response rate = 27.5%, n = 11); the five-year progression-free survival and overall survival were 20.3 and 66.5%, respectively. In conclusion, high-dose chemotherapy with tandem auto-PBSCT is feasible and safe with a favorable response rate in treating advanced multiple myeloma in Japan.
International journal of hematology 11/2009; 90(5):635-42. · 1.17 Impact Factor
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Yasunobu Abe,
Tetsuhide Ito,
Eishi Baba,
Koji Nagafuji,
Ken Kawabe,
Ilseung Choi,
Yoshiyuki Arita,
Toshihiro Miyamoto,
Takanori Teshima,
Shuji Nakano, Mine Harada
[show abstract]
[hide abstract]
ABSTRACT: Advanced unresectable pancreatic cancer has an extremely poor prognosis despite intensive chemotherapy. As a new therapeutic modality, we investigated nonmyeloablative allogeneic hematopoietic stem cell transplantation from a related donor.
Five patients with chemotherapy-resistant pancreatic cancer received allogeneic peripheral blood stem cell transplantation after a conditioning regimen consisting of low-dose total body irradiation and fludarabine. The prophylaxis for graft-versus-host disease consisted of mycophenolate mofetil and cyclosporine.
The median age of the 5 patients was 54 years, and the median duration from diagnosis to nonmyeloablative allogeneic hematopoietic stem cell transplantation was 10 months. Three of the 5 patients achieved complete donor chimerism of peripheral T cells, at a median time of day 42. Acute graft-versus-host disease developed in 3 patients: grade 2 in 2 patients and grade 1 in 1. Tumor reduction was observed in 2 patients: 1 patient showed disappearance of the pancreatic tumor, and the other patient showed approximately 20% reduction of the tumor. Marked elevation of tumor necrosis factor alpha was observed as the tumor regressed.
Although advanced pancreatic cancer progresses rapidly, some graft-versus-tumor effects and pivotal role of tumor necrosis factor alpha were suggested. To obtain the durable response, patient selection and new strategies become important.
Pancreas 09/2009; 38(7):815-9. · 2.39 Impact Factor
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ABSTRACT: We prospectively evaluated the safety and efficacy of the anti-CD20 chimeric monoclonal antibody rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Seven patients were treated with 375 mg/m(2) rituximab weekly for 4 consecutive weeks. Rituximab was well tolerated with no severe toxicity observed during treatment. At 1 year, 3 patients showed a partial response to rituximab therapy, 3 had stable disease, and 1 had progressive disease. Rituximab allowed a reduction in the dose of steroids in 4 patients. Responsive manifestations included mild to moderate skin and oral lesions, and immune hemolytic anemia, and thrombocytopenia. Severe manifestations involving the skin, fascia, and eye did not respond to treatment. These observations suggest that rituximab therapy may be effective for select patients with corticosteroid-refractory chronic GVHD that is not advanced.
International journal of hematology 07/2009; 90(2):253-60. · 1.17 Impact Factor
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Tomonori Hidaka,
Kotaro Shide,
Haruko Shimoda,
Takurou Kameda,
Keiko Toyama,
Keiko Katayose,
Youko Kubuki,
Kenji Nagata,
Katsuto Takenaka,
Koichi Akashi,
Takashi Okamura,
Yoshiyuki Niho,
Hideaki Mizoguchi,
Mitsuhiro Omine,
Keiya Ozawa, Mine Harada,
Kazuya Shimoda
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ABSTRACT: Cytogenetic abnormalities were often observed in primary myelofibrosis patients. The presence of specific cytogenetic abnormalities, such as sole abnormalities of chromosome 13q-, 20q-, or -7/7q-, is reported to have the influence on the prognosis of primary myelofibrosis. We analyzed the data from the prospective survey of Japanese primary myelofibrosis patients which was conducted from 1999 to clarify the impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis. A total of 202 primary myelofibrosis patients had the cytogenetic and the prognostic data. Eighty (40%) out of 202 cases had cytogenetic abnormalities, and an association was evident for platelet counts. Although the presence of an abnormal karyotype did not affect the prognosis, primary myelofibrosis patients with cytogenetic abnormalities other than 13q- and 20q- showed an inferior prognosis compared to patients with a normal karyotype or sole 13q- or 20q- abnormalities. Patients with an unfavorable cytogenetic profile (abnormal cytogenetics other than 13q- or 20q-) also had a greater tendency to transform to leukemia than patients with a favorable cytogenetic profile (normal cytogenetics, sole abnormalities of either chromosome 13q-, or 20q-). Abnormal cytogenetics other than 13q- or 20q- in primary myelofibrosis patients has the poor prognostic effect for both survival and the risk of leukemic transformation.
European Journal Of Haematology 07/2009; 83(4):328-33. · 2.61 Impact Factor
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The Journal of Rheumatology 07/2009; 36(6):1349-51. · 3.69 Impact Factor
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ABSTRACT: The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit molecule). Expression of the c-kit molecule on the gated leukemic blast cells from newly diagnosed patients with leukemia was analysed by flow cytometry using the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined, significant c-kit-positive blast cells were detected in 24 cases (69%), even though the percentage of positive cells was widely variable. The correlation between the percentage of cells positive for the c-kit molecule and the percentage of cells positive for CD34 was found to be statistically significant (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for lymphoid markers. The mean percentage of the cells expressing c-kit molecule among the lymphoid marker-positive cases was significantly larger than that among the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases were c-kit-negative, including 8 cases which were positive for some myeloid markers. Stem cell factor enhanced the colony growth in five out of six acute myeloblasts leukemia cases expressing the c-kit molecule. On the other hand, SCF did not stimulate colony growth in any of the four cases which were not positive for the c-kit molecule. These findings indicated that the distribution of flow cytometrically detectable c-kit molecules on leukemic cells is related to the morphologic and immunologic classification of these leukemic cells and to the expression of the CD34 cell surface molecule on some myeloid leukemic cells. On such cells, expression of the c-kit molecule may have a functional role and be related to the maturation process.
06/2009; 14(5-6):421-428.
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Katsuto Takenaka,
Katsuji Shinagawa,
Yoshinobu Maeda,
Masanori Makita,
Kozuka,
Atsuko Ashiba,
Yamamoto,
Nobuharu Fujii,
Yuichiro Nawa,
Yasushi Hiramatsu,
Kazutaka Sunami,
Fumihiko Ishimaru,
Tadashi Yoshimo,
Katsuyuki Kiura, Mine Harada
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ABSTRACT: CD56+ natural killer (NK) cell lymphomas occur frequently in the nasal and nasopharyngeal regions and carry a poor prognosis. We have studied seven cases with NK-cell lymphomas. These lymphomas showed the following immunophenotype: CD56+, CD2+, sCD3 and Epstein-Barr virus-encoded small RNAs (EBERs)+. Six patients had localized (stage I or II) disease involving the nasopharyngeal region, while one had stage III disease. One patient with stage I disease achieved a complete remission (CR) after treatment with involved-field irradiation, but subsequently relapsed and died. The remaining six patients received combination chemotherapy as primary treatment: five patients with localized stage I or II disease and one patient with advanced stage III disease. Responses to initial chemotherapy were generally poor. These six patients received a variety of salvage chemotherapy regimens, but never achieved a CR. Subsequently, four of six patients showed a highly aggressive clinical course and died of disseminated disease within 1 year from the diagnosis. Three of six patients received high-dose chemotherapy supported by syngeneic, autologous or allogeneic peripheral blood stem cell transplantation. Two of the three transplant patients achieved a CR and are now surviving in continuous CR. Our clinical experience suggests that myeloablative high-dose chemotherapy and bone marrow rescue by hematopoietic stem cell transplantation may be an effective salvage treatment modality for refractory NK-cell lymphomas and could be considered as a part of the initial therapy for these patients.
06/2009; 42(6):1297-1303.
