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[show abstract]
[hide abstract]
ABSTRACT: Nephrotic syndrome (NS) is a rare complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cases
of 2 patients who developed NS after receiving allo-IISCT for chronic myelogenous leukemia and acute lymphoblastic leukemia
arc described. In both cases, renal biopsy revealed membranous nephropathy (MN), and the patients achieved remission after
treatment with prednisolone. Previously reported cases and our experience suggest that most NS patients show MN in histologic
tests after allo-HSCT and that its development is related to graft-versus-host disease. Rarly treatment with steroids seems
effective for resolving symptoms of NS and improving renal function.
Key wordsNephrotic syndrome-Membranous nephropathy-Hematopoietic stem cell transplantation-Graft-versus-host disease
International Journal of Hematology 04/2012; 79(2):193-197. · 1.27 Impact Factor
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ABSTRACT: Mantle cell lymphoma (MCL) has a poor prognosis without cure; the median overall survival ranges only from 3 to 4 years irrespective
of conventional therapeutic regimens. IDEC-C2B8 (rituximab), a chimeric monoclonal antibody against the B-cell—specific antigen
CD20, induces an evaluable clinical response in patients with MCL with mild toxicities. However, the single agent rituximab
cannot cure MCL. Due to its low immunogenicity, an antibody against IDEC-C2B8 (human anti-chimeric antibody [HACA]) has rarely
been produced in vivo. We report a patient with relapsed MCL who was successfully treated with IDEC-C2B8 for over a year although
she developed HACA 6 months after the initial administration of IDEC-C2B8 in the phase II clinical trial conducted by Zenyaku
Kogyo Co. Ltd. We followed the pharmacokinetics of IDEC-C2B8, the serum HACA titer, and the number of B lymphocytes in the
peripheral blood in relation to clinical response. The HACA became undetectable soon after subsequent administrations of IDEC-C2B8.
When the serum level of IDEC-C2B8 was kept elevated, clinical responses were apparently observed and HACA disappeared during
this response period. There were no significant clinical toxicities related to the appearance of HACA. The present findings
suggested that IDEC-C2B8 is effective and safe even in patients who have developed HACA.
International Journal of Hematology 04/2012; 74(1):70-75. · 1.27 Impact Factor
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Mari Sakai,
Yasushi Miyazaki,
Emi Matsuo,
Yukiyoshi Moriuchi,
Tomoko Hata,
Takuya Fukushima,
Yoshitaka Imaizumi,
Daisuke Imanishi,
Jun Taguchi,
Masako Iwanaga, [......],
Sunao Atogami,
Satoshi Koida,
Tatsuro Joh,
Masaomi Yamamura,
Yuji Matsuo,
Hisashi Soda,
Hiroaki Nonaka,
Itsuro Jinnai,
Kazutaka Kuriyama,
Masao Tomonaga
[show abstract]
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ABSTRACT: Imatinib has dramatically improved long-term survival of chronic myelogenous leukemia (CML) patients. To analyze its efficacy in a practical setting, we registered most of CML patients in Nagasaki Prefecture of Japan. Of these, 73 patients received imatinib as an initial therapy. The overall survival rate of these patients was 88.7% at 6 years, and the cumulative complete cytogenetic response rate was 82.5% at 18 months. These results are comparable with the data of other reports including the IRIS study; however, the administered imatinib dose was smaller in our study than that in other reports. To address these discrepancies, we measured the trough concentration of imatinib among 35 patients. Although 39% of the patients were administered less than 400 mg/day, the trough level was comparable to those of previous reports. The trough level of imatinib showed a significant relationship with its efficacy, and was clearly related to dose of imatinib administrated and dose of imatinib divided by body surface area (BSA). Considering the smaller BSA of Japanese patients as compared to those of foreign origin, the results suggest that a lower dose of imatinib could maintain enough trough level and provided excellent results for the treatment of CML in our registry.
International journal of hematology 05/2009; 89(3):319-25. · 1.17 Impact Factor
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[hide abstract]
ABSTRACT: Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.
British Journal of Haematology 10/2008; 116(1):94 - 102. · 4.94 Impact Factor
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Emi Matsuo,
Yasushi Miyazaki, Chizuko Tsutsumi,
Yoriko Inoue,
Reishi Yamasaki,
Tomoko Hata,
Takuya Fukushima,
Hideki Tsushima,
Daisuke Imanishi,
Yoshitaka Imaizumi, [......],
Yoshiharu Yoshida,
Yuji Matsuo,
Hiroaki Nonaka,
Tatsuro Joh,
Yumi Takasaki,
Chiyuki Kawasaki,
Saburo Momita,
Itsuro Jinnai,
Kazutaka Kuriyama,
Masao Tomonaga
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the efficacy of imatinib in a practical setting, we registered 43 patients with newly diagnosed chronic myelogenous leukemia (CML) (group I) and 56 patients with previously diagnosed CML (group II) at 11 hematology centers in Nagasaki prefecture, Japan, from December 2001 to July 2005 and analyzed the molecular responses. Cytopenia, fluid retention, and skin rash were major adverse events, along with elevation in creatine phosphokinase levels. With a follow-up of approximately 3.5 years, imatinib treatment led to 88.7% overall survival (OS) and 85.2% progression-free survival (PFS) rates for group I, and 79.8% OS and 76.6% PFS rates for group II; the rates were not significantly different despite a lower average imatinib dose in group II. The rates of complete cytogenetic response at 30 months and major molecular response at 24 months were 86.1% and 62.5%, respectively, in group I, and 77.9% and 58.3% in group II; the rates were not significantly different. As has been reported by other groups, these results demonstrate that imatinib treatment can provide excellent clinical and molecular effects for not only newly diagnosed but also previously treated CML patients in practical settings that cover a wider variety of patients than clinical trials.
International Journal of Hematology 03/2007; 85(2):132-9. · 1.27 Impact Factor
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Jun Taguchi,
Yasushi Miyazaki, Chizuko Tsutsumi,
Yasushi Sawayama,
Koji Ando,
Hideki Tsushima,
Takuya Fukushima,
Tomoko Hata,
Shinichiro Yoshida,
Kazutaka Kuriyama,
Sumihisa Honda,
Itsuro Jinnai,
Hiroyuki Mano,
Masao Tomonaga
[show abstract]
[hide abstract]
ABSTRACT: We previously reported that the percentage of myeloperoxidase (MPO) positive blasts had a prognostic impact on survival of patients with acute myeloid leukemia (AML). To extend this observation, we quantitatively measured the level of the MPO gene in AC133 positive leukemia cells that would contain a putative AML stem/progenitor compartment. AML cases were divided into the MPO gene high (MPOg-H) and MPO gene low (MPOg-L) groups. Only patients belonging to the MPOg-H group had a favorable chromosomal translocation, t(8;21), and having no morphological dysplasia that was associated with MPOg-L. The difference in the survival of MPOg-H and MPOg-L was statistically meaningful, demonstrating the possible prognostic impact of the expression of MPO gene in AC133 positive leukemia cells.
Leukemia Research 10/2006; 30(9):1105-12. · 2.92 Impact Factor
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Yoriko Inoue,
Hideki Tsushima,
Koji Ando,
Yasushi Sawayama,
Mari Sakai,
Reishi Yamasaki,
Emi Matsuo, Chizuko Tsutsumi,
Yoshitaka Imaizumi,
Masako Iwanaga,
Daisuke Imanishi,
Jun Taguchi,
Yasushi Miyazaki,
Masao Tomonaga
[show abstract]
[hide abstract]
ABSTRACT: Normal and malignant hematopoietic cells are shown to express and secrete various cytokines and chemokines, some of which are believed to play an important role in normal and abnormal hematopoiesis in an autocrine/paracrine manner. To explore the possibility of a cytokine/chemokine network participating in the pathophysiology of anemic disorders, we evaluated the ability of inflammatory cytokines to induce chemokine expression using erythroid progenitor cells.
Erythropoietin-dependent human leukemia cell line AS-E2 was used as a model of erythroid colony-forming unit (CFU-E) cells. The expression of mRNA of 8 chemokines was examined using RT-PCR, before and after TNF-alpha, IFN-gamma, and IL-1beta stimulation. For MIP-3alpha, the promoter activity was analyzed by luciferase assay and secretion was confirmed by ELISA. The expression of CCR6, the specific receptor for MIP-3alpha, was analyzed by RT-PCR and flow cytometry.
Unstimulated AS-E2 cells constitutively expressed transcripts for MCP-4, IP-10, PF-4, IL-8, and MIP-3alpha. Stimulation with TNF-alpha, IFN-gamma, and IL-1beta upregulated MIP-3alpha mRNA expression and induced its protein secretion. Luciferase assay revealed that these cytokines could upregulate promoter activity of the MIP-3alpha gene, possibly through the NF-kappaB pathway. CCR6 mRNA was detected and its intracellular expression was confirmed.
These data suggest that inflammatory cytokine-stimulated erythroid progenitors secrete MIP-3alpha, which may function in an autocrine/paracrine manner. Furthermore, the existence of intracellular CCR6 suggests the involvement in cytokine signaling of a MIP-3alpha-dependent internal autocrine mechanism. These mechanisms may play a role in pathophysiology of anemic disorders, such as secondary anemia and bone marrow failure syndromes.
Experimental Hematology 02/2006; 34(1):19-26. · 2.90 Impact Factor
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Chizuko Tsutsumi,
Masuzu Ueda,
Yasushi Miyazaki,
Yoshihiro Yamashita,
Young Lim Choi,
Jun Ota,
Ruri Kaneda,
Koji Koinuma,
Shin-ichiro Fujiwara,
Hiroyuki Kisanuki,
Madoka Ishikawa,
Keiya Ozawa,
Masao Tomonaga,
Hiroyuki Mano
[show abstract]
[hide abstract]
ABSTRACT: Acute myeloid leukemia (AML) develops de novo or secondarily to either myelodysplastic syndrome (MDS) or anticancer treatment (therapy-related leukemia, TRL). Prominent dysplasia of blood cells is apparent in individuals with MDS-related AML as well as in some patients with TRL or even with de novo AML. The clinical entity of AML with multilineage dysplasia (AML-MLD) is likely to be an amalgamation of MDS-related AML and de novo AML-MLD. The aim of this study was to clarify, by the use of high-density oligonucleotide microarrays, whether these subcategories of AML are intrinsically distinct from each other.
The AC133+ hematopoietic stem cell-like fractions were purified from the bone marrow of individuals with de novo AML without dysplasia (n = 15), AML-MLD (n = 11), MDS-related AML (n = 11), or TRL (n = 2), and were subjected to the synthesis of cRNA which was subsequently hybridized to microarray harboring oligonucleotide corresponding to more than 12,000 probe sets.
We could identify many genes whose expression was specific to these various subcategories of AML. Furthermore, with the correspondence analysis/three-dimensional projection strategy, we were able to visualize the independent, yet partially overlapping, nature of current AML subcategories on the basis of their transcriptomes.
Our data indicate the possibility of subclassification of AML based on gene expression profiles of leukemic blasts.
Experimental Hematology 10/2004; 32(9):828-35. · 2.90 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Nephrotic syndrome (NS) is a rare complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cases of 2 patients who developed NS after receiving allo-HSCT for chronic myelogenous leukemia and acute lymphoblastic leukemia are described. In both cases, renal biopsy revealed membranous nephropathy (MN), and the patients achieved remission after treatment with prednisolone. Previously reported cases and our experience suggest that most NS patients show MN in histologic tests after allo-HSCT and that its development is related to graft-versus-host disease. Early treatment with steroids seems effective for resolving symptoms of NS and improving renal function.
International Journal of Hematology 03/2004; 79(2):193-7. · 1.27 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: ETS proteins (such as PU.1, Fli-1 and ETS-1) have been shown to play important roles in normal and abnormal hematopoiesis. We examined the expression of the ELF subfamily of ETS genes (ELF-1, MEF and NERF) in acute myeloid leukemia (AML) cells using Northern blot analysis. ELF-1 and MEF were expressed in all samples, whereas NERF was not. The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P<0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype. The pattern of MEF expression was not uniform among cells with CD34(+)/CD33(+). It is suggested that the low RE of MEF might be part of a gene expression profile characterizing AML with a good prognosis.
Leukemia Research 05/2003; 27(5):387-92. · 2.92 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.
British Journal of Haematology 02/2002; 116(1):94-102. · 4.94 Impact Factor
