Published Papers - Fukushima Takuya

A Comprehensive Study of the Immunophenotype and its Clinicopathologic Significance in Adult T-Cell Leukemia/Lymphoma.

Tomoko Tamaki, Kennosuke Karube, Shugo Sakihama, Yuma Tsuruta, Ryoko Awazawa, Masaki Hayashi, Norihiro Nakada, Hirofumi Matsumoto, Nobutake Yagi, Kazuiku Ohshiro, Iwao Nakazato, Sakiko Kitamuraj , Yukiko Nishij , Takuya Miyagi, Sayaka Yamaguchi, Sawako Nakachi, Satoko Morishima, Hiroaki Masuzaki, Kenzo Takahashi, Takuya Fukushima, Naoki Wada

Modern Pathology   38 ( 8 ) 100169   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL)

Tanaka Y, Tanaka R, Imaizumi N, Mizuguchi M, Takahashi Y, Hayashi M, Miyagi T, Uchihara J, Ohshiro K, Masuzaki H, Fukushima T.

Frontier Immunology     2022.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Clinically amyopathic dermatomyositis manifested after the allogeneic haematopoietic stem cell transplantation: Case presentation and literature review

Riko Miyagi, Sawako Nakachi, Yasutaro Tamaki, Mototsugu Doi, Tomo Nakajima, Sakiko Kitamura, Shohei Tomori, Taeko Hanashiro, Keita Tamaki, Kazuho Morichika, Yukiko Nishi, Satoko Morishima, Takuya Fukushima, Hiroaki Masuzaki

Modern Rheumatology Case Reports   7 ( 1 ) 102 - 107   2022.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Acute type adult T-cell leukemia cells proliferate in the lymph nodes rather than in peripheral blood

Mariko Mizuguchi, Mitsuyoshi Takatori, Shugo Sakihama, Manami Yoshita-Takahashi, Naoki Imaizumi, Yoshiaki Takahashi, Hiroo Hasegawa, Kennosuke Karube, Takuya Fukushima, Masataka Nakamura, Yuetsu Tanaka

Cancer Gene Therapy   29 ( 11 ) 1570 - 1577   2022.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Elevation of the Plasma Levels of TNF Receptor 2 in Association with Those of CD25, OX40, and IL-10 and HTLV-1 Proviral Load in Acute Adult T-Cell Leukemia

Kato M, Imaizumi N, Tanaka R, Mizuguchi M, Hayashi M, Miyagi T, Uchihara J, Ohshiro K, Todoroki J, Karube K, Masuzaki H, Tanaka Y, Fukushima T.

Viruses   14 ( 4 ) 751   2022.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Impact of anti-diabetic sodium-glucose cotransporter 2 inhibitors on tumor growth of intractable hematological malignancy in humans.

Nakachi S, Okamoto S, Tamaki K, Nomura I, Tomihama M, Nishi Y, Fukushima T, Tanaka Y, Morishima S, Imamura M, Maeda S, Tsutsui M, Matsushita M, Masuzaki H.

Biomedicine & Pharmacotherapy   149   112864   2022.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Full-length HLA sequencing in adult T cell leukemia-lymphoma uncovers multiple gene alterations

Tamaki K, Morishima S, Suzuki S, Shigenari A, Nomura I, Yokota Y, Morichika K, Nishi Y, Nakachi S, Okamoto S, Fukushima T, Shiina T, Masuzaki H.

Leukemia   35 ( 10 ) 2998 - 3001   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma

Morichika K, Karube K, Sakihama S, Watanabe R, Kawaki M, Nishi Y, Nakachi S, Okamoto S, Takahara T, Satou A, Shimada S, Shimada K, Tsuzuki T, Fukushima T, Morishima S, Masuzaki H.

The American Journal of Surgical Pathology   45 ( 6 ) 832 - 840   2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Genetic profile of adult T-cell leukemia/lymphoma in Okinawa: Association with prognosis, ethnicity, and HTLV-1 strains

Sakihama S, Morichika K, Saito R, Miyara M, Miyagi T, Hayashi M, Uchihara J, Tomoyose T, Ohshiro K, Nakayama S, Nakachi S, Morishima S, Sakai K, Nishio K, Masuzaki H, Fukushima T, Karube K.

Cancer Science   112 ( 3 ) 1300 - 1309   2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Clinicopathological features of adult T-cell leukemia/lymphoma with HTLV-1-infected Hodgkin and Reed-Sternberg-like cells

Karube K, Takatori M, Sakihama S, Tsuruta Y, Miyagi T, Morichika K, Kitamura S, Nakada N, Hayashi M, Tomori S, Nakazato I, Ohshiro K, Imaizumi N, Kikuti YY, Nakamura N, Morishima S, Masuzaki H, Fukushima T.

Blood Advances   5 ( 1 ) 198 - 206   2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A new diagnostic algorithm using biopsy specimens in adult T-cell leukemia/lymphoma: combination of RNA in situ hybridization and quantitative PCR for HTLV-1.

Takatori M, Sakihama S, Miyara M, Imaizumi N, Miyagi T, Ohshiro K, Nakazato I, Hayashi M, Todoroki J, Morishima S, Masuzaki H, Fukushima T, Karube K

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc ( Modern Pathology )    2020.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma.

Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Sakai R, Fukushima N, Fukushima T, Moriuchi Y, Itoh K, Nosaka K, Choi I, Sawa M, Okamoto R, Tsujimura H, Uchida T, Suzuki S, Okamoto M, Takahashi T, Sugiura I, Onishi Y, Kohri M, Yoshida S, Kojima M, Takahashi H, Tomita A, Atsuta Y, Maruyama D, Tanaka E, Suzuki T, Kinoshita T, Ogura M, Ueda R, Mizokami M

Journal of hepatology   73 ( 2 ) 285 - 293   2020.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND & AIMS: The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitive HBsAg assay using prospectively stored samples of HBV DNA monitoring study for lymphoma patients with resolved HBV infection following anti-CD20 antibody, rituximab-containing chemotherapy (UMIN000001299). METHODS: HBV reactivation defined as HBV DNA levels of 11 IU/mL or more was confirmed in 22 of 252 patients. Conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/mL) and ultra-high sensitive HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/mL) were measured at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. RESULTS: Baseline HBsAg was detected using ICT-CLEIA in 4 patients, in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the discrepant 5 patients undetectable by ICT-CLEIA, 2 patients resolved spontaneously. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/mL, detected HBV DNA below the level of quantification, and detected ICT-CLEIA HBsAg at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p<0.05). CONCLUSIONS: A novel ICT-CLEIA HBsAg assay would be an alternative method to diagnose HBV reactivation.

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Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL.

Guerrero CLH, Yamashita Y, Miyara M, Imaizumi N, Kato M, Sakihama S, Hayashi M, Miyagi T, Karimata K, Uchihara J, Ohshiro K, Todoroki J, Nakachi S, Morishima S, Karube K, Tanaka Y, Masuzaki H, Fukushima T

Blood advances ( Blood Advances )  4 ( 6 ) 1062 - 1071   2020.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Ectonucleotidase CD39 is highly expressed on ATLL cells and is responsible for their immunosuppressive function.

Nagate Y, Ezoe S, Fujita J, Okuzakis D, Motooka D, Ishibashi T, Ichii M, Tanimura A, Kurashige M, Morii E, Fukushima T, Suehiro Y, Yokota T, Shibayama H, Oritani K, Kanakura Y

Leukemia ( Leukemia )    2020.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan.

Mizuguchi M, Takahashi Y, Tanaka R, Fukushima T, Tanaka Y

Pathogens (Basel, Switzerland) ( Pathogens )  9 ( 2 )   2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Approximately one-tenth of the 10 million individuals living with human T-cell leukemia virus type-1 (HTLV-1) worldwide live in Japan. Most of these infected individuals live in the southwest region of Japan, including Okinawa prefecture; however, currently no prophylactic vaccine against HTLV-1 infection is available. For preventing the HTLV-1 spread, we previously generated a humanized monoclonal antibody (hu-LAT-27) that mediates both neutralization and antibody-dependent cellular cytotoxicity (ADCC). The neutralization epitope of LAT-27 is a linear amino acid sequence from residue 191 to 196 (Leu-Pro-His-Ser-Asn-Leu) of the HTLV-1 envelope gp46 protein. Here, we found that the LAT-27 epitope is well conserved among HTLV-1 clinical isolates prevalent in Okinawa. The hu-LAT-27 treatment inhibited syncytium formation by these clinical HTLV-1 isolates. Although an amino acid substitution at residue 192 in the LAT-27 epitope from proline to serine was found in a few HTLV-1 isolates, hu-LAT-27 could still react with a synthetic peptide carrying this amino acid substitution. These findings demonstrate the wide spectrum of hu-LAT-27 reactivity, suggesting that hu-LAT-27 may be a candidate drug for prophylactic passive immunization against HTLV-1 infection.

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Transplant-related complications are impediments to the success of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia patients in non-complete remission.

Tomori S, Morishima S, Nishi Y, Nakachi S, Tamaki K, Morichika K, Tedokon I, Shimabukuro N, Hanashiro T, Kitamura S, Uchibori S, Miyagi R, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tomoyose T, Karube K, Fukushima T, Masuzaki H

Bone marrow transplantation ( Bone Marrow Transplantation )  55 ( 1 ) 233 - 241   2020.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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EOS, an Ikaros family zinc finger transcription factor, interacts with the HTLV-1 oncoprotein Tax and is downregulated in peripheral blood mononuclear cells of HTLV-1-infected individuals, irrespective of clinical statuses.

Naito T, Ushirogawa H, Fukushima T, Tanaka Y, Saito M

Virology journal ( Virology Journal )  16 ( 1 ) 160   2019.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T-cell leukemia/lymphoma.

Morichika K, Karube K, Kayo H, Uchino S, Nishi Y, Nakachi S, Okamoto S, Morishima S, Ohshiro K, Nakazato I, Fukushima T, Masuzaki H

Cancer science ( Cancer Science )  110 ( 9 ) 2982 - 2991   2019.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adipose tissue-derived mesenchymal stem cells ameliorate bone marrow aplasia related with graft-versus-host disease in experimental murine models.

Nishi Y, Murakami A, Murayama Y, Tsukahara N, Okamoto S, Nakachi S, Morichika K, Tamaki K, Noguchi H, Matsushita M, Karube KN, Fukushima T, Morishima S, Kishimoto H, Masuzaki H

Transpl Immunol   55   101205 - 101205   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Possibility of a risk-adapted treatment strategy for untreated aggressive adult T-cell leukaemia-lymphoma (ATL) based on the ATL prognostic index: a supplementary analysis of the JCOG9801.

Toyoda K, Tsukasaki K, Machida R, Kadota T, Fukushima T, Ishitsuka K, Maruyama D, Nagai H

British journal of haematology ( British Journal of Haematology )  186 ( 3 ) 440 - 447   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adipose tissue-derived mesenchymal stem cells ameliorate bone marrow aplasia related with graft-versus-host disease in experimental murine models.

Nishi Y, Murakami A, Murayama Y, Tsukahara N, Okamoto S, Nakachi S, Morichika K, Tamaki K, Noguchi H, Matsushita M, Karube KN, Fukushima T, Morishima S, Kishimoto H, Masuzaki H

Transplant immunology ( Transplant Immunology )  55   101205   2019.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Cytomegalovirus reactivation is associated with increased mortality more than 100 days after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma.

Sawayama Y, Itonaga H, Fukushima T, Nakano N, Fujiwara H, Utsunomiya A, Fukuda T, Miyamoto T, Eto T, Miyashita K, Nakamae H, Ogata M, Yamanoha A, Miyazaki Y, Kanda J, Atsuta Y, Kato K, ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation.

American journal of hematology ( American Journal of Hematology )  94 ( 5 ) E143 - E146   2019.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report.

Cook LB, Fuji S, Hermine O, Bazarbachi A, Ramos JC, Ratner L, Horwitz S, Fields P, Tanase A, Bumbea H, Cwynarski K, Taylor G, Waldmann TA, Bittencourt A, Marcais A, Suarez F, Sibon D, Phillips A, Lunning M, Farid R, Imaizumi Y, Choi I, Ishida T, Ishitsuka K, Fukushima T, Uchimaru K, Takaori-Kondo A, Tokura Y, Utsunomiya A, Matsuoka M, Tsukasaki K, Watanabe T

Journal of clinical oncology : official journal of the American Society of Clinical Oncology ( Journal of Clinical Oncology )  37 ( 8 ) 677 - 687   2019.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Association of high levels of plasma OX40 with acute adult T-cell leukemia.

Tanaka Y, Takahashi Y, Tanaka R, Miyagi T, Saito M, Fukushima T

International journal of hematology ( International Journal of Hematology )  109 ( 3 ) 319 - 327   2019.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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JSH Practical Guidelines for Hematological Malignancies, 2018: II. Lymphoma-8. Adult T-cell leukemia-lymphoma.

Tsukasaki K, Fukushima T

International journal of hematology ( International Journal of Hematology )  109 ( 3 ) 249 - 259   2019.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Association of high levels of plasma OX40 with acute adult T-cell leukemia.

Tanaka Y, Takahashi Y, Tanaka R, Miyagi T, Saito M, Fukushima T

International Journal of Hematology   109 ( 3 ) 319 - 327   2019.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Intestinal helminth infections in HIV-infected patients in Savannakhet after establishment of an HIV registration network in Lao People's Democratic Republic.

Kaneshiro Y, Sourinphoumy K, Imaizumi N, Rasaphon M, Kuba-Miyara M, Sakihama S, Guerrero CLH, Nhativong K, Nonaka D, Pongvongsa T, Kobayashi J, Kounnavong S, Fukushima T

Tropical medicine and health ( Tropical Medicine and Health )  47 ( 1 ) 14   2019 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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[Adult T-cell leukemia-lymphoma: ATL].

Fukushima T

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人 日本血液学会 )  60 ( 3 ) 247 - 248   2019 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma.

Toriyama E, Imaizumi Y, Taniguchi H, Taguchi J, Nakashima J, Itonaga H, Sato S, Ando K, Sawayama Y, Hata T, Fukushima T, Miyazaki Y

International journal of hematology ( International Journal of Hematology )  108 ( 2 ) 167 - 175   2018.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult T-cell leukemia-lymphoma (ATL) is an intractable hematopoietic malignancy with a very poor prognosis. Although improved responses have been achieved through intensive chemotherapy in newly diagnosed patients with aggressive ATL, most patients suffer from relapse or disease recurrence, and an effective salvage therapy, especially for candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT), is yet to be established. The efficacy of the EPOCH regimen has been reported for several lymphoid malignancies; however, its efficacy for ATL has not been sufficiently evaluated. Here, we report results of a study of the EPOCH regimen as a salvage therapy for ATL. We retrospectively analyzed patients with relapsed or refractory ATL treated in our institution, with EPOCH as a first salvage therapy. Fourteen patients with a median age of 58 years were analyzed, among whom eight achieved a response, including a complete response in one patient and partial responses in seven. Seven patients underwent allo-HSCT after EPOCH therapy; however, the median overall survival (OS) could not be determined, whereas OS at 2 years after allo-HSCT was estimated to be 85.7%. These results suggest that EPOCH is an option for salvage therapy in patients with ATL, including candidates for allo-HSCT.

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Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.

Tamaki K, Morishima S, Nomura S, Nishi Y, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Taira N, Tomoyose T, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Uchihara JN, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Fukushima T, Masuzaki H

Cancer science ( Cancer Science )  109 ( 7 ) 2286 - 2293   2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.

玉城啓太, 福島 卓也ほか

Cancer Science   109 ( 7 ) 2286 - 2293   2018.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Clinical usefulness of FDG-PET/CT for the evaluation of various types of adult T-cell leukemia.

Nakachi S, Okada M, Morishima S, Agarie Y, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tamaki K, Tedokon I, Morichika K, Nishi Y, Tomoyose T, Karube K, Fukushima T, Murayama S, Masuzaki H

Hematology (Amsterdam, Netherlands) ( TAYLOR & FRANCIS LTD )  22 ( 9 ) 536 - 543   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Purpose: The aim was to explore undefined useful indices for clinically grading adult T-cell leukemia (ATL) using [F-18] 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography/computed tomography (PET/CT). Methods: A total of 28 patients with ATL (indolent, 9; aggressive, 19) were enrolled; all patients with aggressive ATL underwent FDG-PET/CT before chemotherapy. Patients with indolent ATL underwent FDG-PET/CT at the time of suspected disease progression and/or transformation; some received lymph node biopsy. The quantitative parameters maximum standardized uptake values (SUVmax), and mean and peak SUV, metabolic tumor volume (MTV), and volume-based total lesion glycolysis were calculated with the margin threshold as 25%, and 50% of the SUVmax for all lesions. Results: All parameters except for MTV-25% showed significant differences (P0.05) in differentiating the aggressive type from the indolent type of ATL. Areas under the curve for receiver-operating characteristic (ROC) analysis regarding the series of parameters investigated ranged from 0.75 to 0.92; this indicated relatively high accuracy in distinguishing the aggressive type from the indolent type. No malignant findings were detected in lymph node biopsies in indolent ATL patients with lymphadenopathy. Discussion: We performed evaluation of a line of parameters of FDG-PET, thereby demonstrating their significantly high accuracy for grading malignancy in ATL patients. In particular, low accumulation of FDG in indolent ATL patients with lymphadenopathy might predict that it is not a sign of disease transformation, but rather a reactive manifestation. Conclusion: FDG-PET/CT findings could be useful for clinically grading ATL.

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Human T-cell leukemia virus type I Tax genotype analysis in Okinawa, the southernmost and remotest islands of Japan: Different distributions compared with mainland Japan and the potential value for the prognosis of aggressive adult T-cell leukemia/lymphoma.

Sakihama S, Saito M, Kuba-Miyara M, Tomoyose T, Taira N, Miyagi T, Hayashi M, Kinjo S, Nakachi S, Tedokon I, Nishi Y, Tamaki K, Morichika K, Uchihara JN, Morishima S, Karube KN, Tanaka Y, Masuzaki H, Fukushima T

Leukemia research ( PERGAMON-ELSEVIER SCIENCE LTD )  61   18 - 24   2017.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Okinawa, comprising remote islands off the mainland of Japan, is an endemic area of human T-cell leukemia virus type I (HTLV-1), the causative virus of adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). We investigated the tax genotype of HTLV-1 among 29 HTLV-1 carriers, 74 ATL patients, and 33 HAM patients in Okinawa. The genotype distribution-60 (44%) taxA cases and 76 (56%) taxB cases-differed from that of a previous report from Kagoshima Prefecture in mainland Japan (taxA, 10%; taxB, 90%). A comparison of the clinical outcomes of 45 patients (taxA, 14; taxB, 31) with aggressive ATL revealed that the overall response and 1-year overall survival rates for taxA (50% and 35%, respectively) were lower than those for taxB (71% and 49%, respectively). In a multivariate analysis of two prognostic indices for aggressive ATL, Japan Clinical Oncology Group-Prognostic Index and Prognostic Index for acute and lymphoma ATL, with respect to age, performance status, corrected calcium, soluble interleukin-2 receptor, and tax genotype, the estimated hazard ratio of taxA compared with taxB was 2.68 (95% confidence interval, 0.87-8.25; P=0.086). Our results suggest that the tax genotype has clinical value as a prognostic factor for aggressive ATL.

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Prevalence of plasma autoantibody against cancer testis antigen NY-ESO-1 in HTLV-1 infected individuals with different clinical status.

Shiohama Y, Naito T, Matsuzaki T, Tanaka R, Tomoyose T, Takashima H, Fukushima T, Tanaka Y, Saito M

Virology journal ( BIOMED CENTRAL LTD )  14 ( 1 ) 130   2017.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Detection of specific immune responses against cancer/testis antigen NY-ESO-1 was recently reported in patients with adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-infected asymptomatic carriers (ACs). However, the relationship of the responses with the HTLV-1 proviral load (PVL) and the levels of viral gene expression remain unclear. Findings: We measured plasma levels of autoantibodies to NY-ESO-1 immunogenic tumor antigen in HTLV-1-infected individuals with different clinical status, and in healthy controls. Data were compared to tax and HBZ mRNA levels, and PVL. Plasma anti-NY-ESO-1 antibody was detectable in 13.7% (7/51) of ACs, 29.2% (38/130) of patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and 18.9% (10/53) of patients with ATL. Anti-NY-ESO-1 plasma levels were significantly higher in patients with HAM/TSP than in patients with ATL or ACs. Anti-NY-ESO-1 levels were not associated with PVL or the expression levels of tax and HBZ mRNA among HTLV-1-infected individuals, regardless of clinical status. Conclusions: The present results indicate the strong humoral immune response against NY-ESO-1 in natural HTLV-1 infection, irrespective of the clinical status. The higher immunoreactivity against NY-ESO-1 is not simply associated with the levels of both HTLV-1 gene expression and the number of infected cells in vivo. Rather, it might reflect chronic and generalized immune activation in infected individuals.

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Overview

Toshiki Watanabe, Takuya Fukushima

Adult T-cell Leukemia/Lymphoma ( Springer Japan )    1 - 2   2017.04

Type of publication: Research paper (scientific journal)

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Prognosis and prognostic index

Takuya Fukushima

Adult T-cell Leukemia/Lymphoma ( Springer Japan )    109 - 116   2017.04

Type of publication: Research paper (scientific journal)

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An atypical case of late-onset systemic lupus erythematosus with systemic lymphadenopathy and severe autoimmune thrombocytopenia/neutropenia mimicking malignant lymphoma.

Tamaki K, Morishima S, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Nishi Y, Tomoyose T, Karube K, Fukushima T, Masuzaki H

International journal of hematology ( SPRINGER JAPAN KK )  105 ( 4 ) 526 - 531   2017.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Here, we report a rare case of systemic lupus erythematosus (SLE) with conspicuous manifestation of hematological abnormalities. At onset, the 52-year-old male patient showed systemic lymphadenopathy and splenomegaly, severe autoimmune thrombocytopenia, and autoimmune neutropenia. Bone marrow examination and lymph node biopsy excluded the possibility of malignant lymphoma. Based on laboratory findings, he was finally diagnosed with combined autoimmune cytopenia coupled with SLE. Atypical clinical manifestations of SLE prompted us to explore the possibility of autoimmune lymphoproliferative syndrome (ALPS). However, we did not detect an increased number of CD4(-)/CD8(-), CD3(+), TCR alpha beta(+) double-negative T cells in the circulating blood or dysfunctional T cell apoptosis in the Fas/Fas ligand pathway due to mutations in the FAS, FASLG or CASP10 genes. Combined autoimmune cytopenia is a rare clinical entity that in some cases co-occurs with other autoimmune diseases. Given that most SLE patients presenting atypical hematological manifestations at an early stage subsequently exhibit typical systemic manifestations, the present case raises the possibility that initial hematological abnormalities may be signs of unexpected SLE manifestations.

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Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T-cell leukemia-derived cells.

Nasu K, Yamaguchi K, Takanashi T, Tamai K, Sato I, Ine S, Sasaki O, Satoh K, Tanaka N, Tanaka Y, Fukushima T, Harigae H, Sugamura K

Cancer science ( WILEY )  108 ( 3 ) 435 - 443   2017.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells. We then sorted ST1 cells by high or low CA9 expression and established ST1-CA9(high) and ST1-CA9(low) sublines. ST1-CA9(high) cells, like ST1-N6 cells, were more strongly tumorigenic than ST1-CA9(low) or parental ST1 cells when injected into NOG mice. Knockdown of CA9 with shRNAs suppressed the ability of ST1-CA9(high) cells to initiate tumors, and the tumorigenicity of ST1 cells was significantly enhanced by introducing wild-type CA9 or a CA9 mutant with deletion of an intracytoplasmic domain. However, a CA9 with point mutations in the catalytic site did not increase the tumorigenicity of ST1 cells. Furthermore, we detected a small population of CA9(+)CD25(+) cells in lymph nodes of ATL patients. These findings suggest that CA9, and particularly its carbonic anhydrase activity, promotes the tumorigenicity of ATL-derived cells and may be involved in malignant development of lymphoma-type ATL.

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孤立性脊髄硬膜外顆粒球肉腫で発症した急性骨髄性白血病の1例

北村 紗希子, 益崎 裕章, 森島 聡子, 玉城 啓太, 仲地 佐和子, 手登根 伊織, 島袋 奈津紀, 花城 多恵子, 玉城 智子, 福島 卓也

日本内科学会雑誌 ( 一般社団法人 日本内科学会 )  106 ( 10 ) 2214 - 2221   2017 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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<p>28歳，男性．7カ月持続する臀部痛と左下腿運動麻痺があり，MRI（magnetic resonance imaging）で脊柱管内に腫瘤性病変を認め，精査で孤立性顆粒球肉腫の診断に至ったが，治療開始直前に急性骨髄性白血病に移行した．寛解導入療法後に分子遺伝学的寛解に到達し，地固め療法後に既往の統合失調症が増悪し治療中断となったが，22カ月経過した現在も完全寛解を維持している．顆粒球肉腫は急性骨髄性白血病に準じた治療が必要とされ，正確な診断と早期の治療介入が重要である．</p>

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Characterization of patients with aggressive adult T-cell leukemia-lymphoma in Okinawa, Japan: a retrospective analysis of a large cohort.

Nishi Y, Fukushima T, Nomura S, Tomoyose T, Nakachi S, Morichika K, Tedokon I, Tamaki K, Shimabukuro N, Taira N, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Arakaki H, Uchihara JN, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Masuzaki H

International journal of hematology ( SPRINGER JAPAN KK )  104 ( 4 ) 468 - 75   2016.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Okinawa Prefecture, located in the subtropics, is an area of endemic adult T-cell leukemia-lymphoma (ATL) in Japan. We retrospectively analyzed 659 patients with aggressive ATL in seven institutions in Okinawa between 2002 and 2011. The median patient age was 68 years. More patients were aged aeyen90 years (2.6 %), in this study, than in a nationwide survey (&lt; 1 %). The median survival time (MST) of the entire cohort was 6.5 months. Of the 217 patients who had a clinical status similar to that stated in the eligibility criteria of JCOG9801 (a randomized phase III study comparing VCAP-AMP-VECP with CHOP-14), 147 who received the CHOP regimen had a poorer MST than those in the CHOP-14 arm of JCOG9801 (8 vs 11 months). The prevalence of strongyloidiasis in the ATL patients was much higher (12.4 %) than in the historical cohort who visited the University of the Ryukyus Hospital (3.4 %). Furthermore, strongyloidiasis may be associated with ATL-related deaths. These findings suggest that, compared with other areas in Japan, in Okinawa, the proportion of patients aged aeyen90 years with clinical features of aggressive ATL is higher, outcomes are poorer, and the disease is associated with a higher prevalence of strongyloidiasis.

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Heat Shock Enhances the Expression of the Human T Cell Leukemia Virus Type-I (HTLV-I) Trans-Activator (Tax) Antigen in Human HTLV-I Infected Primary and Cultured T Cells.

Kunihiro M, Fujii H, Miyagi T, Takahashi Y, Tanaka R, Fukushima T, Ansari AA, Tanaka Y

Viruses ( MDPI AG )  8 ( 7 ) E191   2016.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The environmental factors that lead to the reactivation of human T cell leukemia virus type-1 (HTLV-I) in latently infected T cells in vivo remain unknown. It has been previously shown that heat shock (HS) is a potent inducer of HTLV-I viral protein expression in long-term cultured cell lines. However, the precise HTLV-I protein(s) and mechanisms by which HS induces its effect remain ill-defined. We initiated these studies by first monitoring the levels of the trans-activator (Tax) protein induced by exposure of the HTLV-I infected cell line to HS. HS treatment at 43 degrees C for 30 min for 24 h led to marked increases in the level of Tax antigen expression in all HTLV-I-infected T cell lines tested including a number of HTLV-I-naturally infected T cell lines. HS also increased the expression of functional HTLV-I envelope gp46 antigen, as shown by increased syncytium formation activity. Interestingly, the enhancing effect of HS was partially inhibited by the addition of the heat shock protein 70 (HSP70)-inhibitor pifithlin-mu (PFT). In contrast, the HSP 70-inducer zerumbone (ZER) enhanced Tax expression in the absence of HS. These data suggest that HSP 70 is at least partially involved in HS-mediated stimulation of Tax expression. As expected, HS resulted in enhanced expression of the Tax-inducible host antigens, such as CD83 and OX40. Finally, we confirmed that HS enhanced the levels of Tax and gp46 antigen expression in primary human CD4(+) T cells isolated from HTLV-I-infected humanized NOD/SCID/gamma c null (NOG) mice and HTLV-I carriers. In summary, the data presented herein indicate that HS is one of the environmental factors involved in the reactivation of HTLV-I in vivo via enhanced Tax expression, which may favor HTLV-I expansion in vivo.

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Absolute quantification of HTLV-1 basic leucine zipper factor (HBZ) protein and its plasma antibody in HTLV-1 infected individuals with different clinical status.

Shiohama Y, Naito T, Matsuzaki T, Tanaka R, Tomoyose T, Takashima H, Fukushima T, Tanaka Y, Saito M

Retrovirology ( BIOMED CENTRAL LTD )  13 ( 1 ) 29   2016.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: Human T cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), which is encoded by a minus strand mRNA, is thought to play important roles in the development of adult T-cell leukemia (ATL) and HTLV1- associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive analysis of HBZ, including mRNA and protein expression, humoral immunoreactivity against HBZ, and HTLV-1 proviral load (PVL), in HTLV1- infected individuals with different clinical status has not been reported previously. Results: In this study, using novel monoclonal antibody-based in-house enzyme-linked immunosorbent assay systems, we report the absolute quantification of HBZ protein and its plasma antibody in clinical samples from HTLV-1-infected individuals with different clinical status. The data were compared to both HBZ mRNA levels and PVL. The results showed that plasma anti-HBZ antibody was detectable only in 10.4 % (5/48) of asymptomatic carriers (ACs), 10.8 % (13/120) of HAM/TSP patients, and 16.7 % (7/42) of ATL patients. HBZ protein was detected in three out of five patients with acute ATL, but was not detected in patients with HAM/TSP (0/10) or ACs (0/4). Thus, an antibody response to HBZ was not associated with the PVL or the expression of HBZ (both at the mRNA and protein levels) or the clinical status of the infection. Conclusions: The present results emphasize the extremely low expression and immunogenicity of HBZ in natural HTLV-1 infection. However, there is a possibility that the low but distinct expression of HBZ protein in PBMCs is associated with the survival of HTLV-1-infected cells and the development of ATL.

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Cord Blood Transplantation Provided Long-term Remission in a Case of Adult T-cell Leukemia-lymphoma (ATL) with Myelofibrosis.

Itonaga H, Taguchi J, Kato T, Sato S, Sawayama Y, Imaizumi Y, Niino D, Hata T, Fukushima T, Ohshima K, Miyazaki Y

Internal medicine (Tokyo, Japan) ( 日本内科学会 )  55 ( 2 ) 197 - 201   2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 53-year-old man was diagnosed with adult T-cell leukemia-lymphoma (ATL) acute type transformed from chronic type. A bone marrow analysis showed diffuse infiltration of abnormal lymphocytes and diffuse fibrotic change. He received unrelated cord blood transplantation (CBT) following reduced-intensity conditioning with complete remission of ATL after two courses of chemotherapy and achieved neutrophil and platelet engraftment. At 99 days after CBT, a bone marrow biopsy showed apparent resolution of myelofibrosis. These results suggest the therapeutic potential of CBT for patients with chemosensitive ATL with myelofibrosis.<br>

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Recurrence of Psoriasis Vulgaris Accompanied by Treatment with C-C Chemokine Receptor Type 4 (CCR4) Antibody (Mogamulizumab) Therapies in a Patient with Adult T cell Leukemia/ Lymphoma: Insight into Autoinflammatory Diseases.

Morichika K, Tomoyose T, Hanashiro T, Shimabukuro N, Tamaki K, Tedokon I, Nishi Y, Nakachi S, Karube KN, Fukushima T, Katoh T, Ohshima K, Masuzaki H

Internal medicine (Tokyo, Japan) ( 一般社団法人 日本内科学会 )  55 ( 10 ) 1345 - 9   2016 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult T cell leukemia / lymphoma (ATL) is one of the most aggressive hematological malignancies caused by human T-lymphotropic virus type-I (HTLV-1). Mogamulizumab is a new defucosylated humanized monoclonal antibody agent which targets C-C chemokine receptor type 4 (CCR4) expressed occasionally on the surface of ATL cells. However, adverse events such as drug eruptions have also been highlighted, at least in part, via the dysfunction of regulatory T cells (Tregs). We herein report a pronounced recurrence of systemic psoriasis vulgaris accompanied by the treatment of mogamulizumab in a patient with ATL. Pathological examinations may suggest a mechanistic link between the recurrence of autoinflammatory diseases and anti-CCR4 antibody therapies.<br>

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Fatal pneumonia and viremia due to human parainfluenza virus type 1 in a patient with adult T-cell leukemia-lymphoma treated with mogamulizumab.

Tamaki K, Kinjo T, Aoyama H, Tomoyose T, Nakachi S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Nishi Y, Taira N, Fujita J, Yoshimi N, Fukushima T, Masuzaki H

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy ( ELSEVIER SCIENCE BV )  21 ( 11 ) 820 - 3   2015.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We report a case of fatal pneumonia and viremia due to human parainfluenza virus type 1 (HPIV-1) in a 65-year-old male patient with adult T-cell leukemia-lymphoma (ATL) treated with mogamulizumab, a brand-new therapeutic agent for ATL. To our knowledge, this is the first report describing viremia due to HPIV-1. After administering mogamulizumab, lymphocyte count in the blood was drastically decreased and the patient suffered from complicated infections including gram-negative bacterial sepsis, cytomegalovirus antigenemia and aspergillosis. Although these infections were successfully controlled by broad spectrum antimicrobial therapy, patchy ground-grass opacities in the both lungs were gradually worsened. He finally died due to acute respiratory failure. Since findings of the chest CT was consistent with typical patterns of viral pneumonia, we screened major respiratory viruses in the peripheral blood with multiplex PCR, and it turned out that RNA of HPIV-1 was positive. Although ATL cells were not detected in the autopsied lungs and a variety of other tissues, cytoplasmic inclusion bodies, which are commonly observed in RNA viral infection, were abundantly observed in the autopsied lung tissue. These findings suggest that mogamulizumab accomplished complete remission of ATL, while the chemotherapy-induced prolonged lymphopenia caused fatal pneumonia and viremia due to HPIV-1. As it has been well recognized that community respiratory viruses including HPIV-1 often cause fatal pneumonia in patients with leukemia, but also there is no specific treatment for HPIV-1, we have to enforce standard precautions especially when we treat leukemic patients with intensively immunosuppressive agents such as mogamulizumab. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study.

Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Takasaki H, Fukushima N, Fukushima T, Moriuchi Y, Itoh K, Nosaka K, Choi I, Sawa M, Okamoto R, Tsujimura H, Uchida T, Suzuki S, Okamoto M, Takahashi T, Sugiura I, Onishi Y, Kohri M, Yoshida S, Sakai R, Kojima M, Takahashi H, Tomita A, Maruyama D, Atsuta Y, Tanaka E, Suzuki T, Kinoshita T, Ogura M, Mizokami M, Ueda R

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America ( OXFORD UNIV PRESS INC )  61 ( 5 ) 719 - 29   2015.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background. There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). Methods. We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of &gt;= 11 IU/mL. Results. With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of &lt;10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P &lt; .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. Conclusions. Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

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Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two case reports and review of the literature

T. Miyagi, H. Itonaga, F. Aosai, J. Taguchi, K. Norose, K. Mochizuki, H. Fujii, A. Furumoto, M. Ohama, K. Karimata, A. Yamanoha, H. Taniguchi, S. Sato, N. Taira, Y. Moriuchi, T. Fukushima, H. Masuzaki, Y. Miyazaki

TRANSPLANT INFECTIOUS DISEASE ( WILEY-BLACKWELL )  17 ( 4 ) 593 - 598   2015.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Toxoplasmic encephalitis represents a rare, but often fatal infection after allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction (PCR)-based preemptive therapy is considered promising for this disease, but is not routinely applied, especially in low seroprevalence countries including Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation that were successfully treated. The diagnosis of toxoplasmic encephalitis in these cases was confirmed by PCR testing when neurological symptoms were observed. Both patients received pyrimethamine and sulfadiazine treatments within 2weeks of the development of neurological symptoms, and remained free of recurrence for 32 and 12months. These results emphasized the importance of the PCR test and immediate treatment after diagnosis for the management of toxoplasmic encephalitis.

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Human T-cell leukemia virus type-I Tax induces the expression of CD83 on T cells.

Tanaka Y, Mizuguchi M, Takahashi Y, Fujii H, Tanaka R, Fukushima T, Tomoyose T, Ansari AA, Nakamura M

Retrovirology ( BIOMED CENTRAL LTD )  12 ( 1 ) 56   2015.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Background: CD83, a cell surface glycoprotein that is stably expressed on mature dendritic cells, can be transiently induced on other hematopoietic cell lineages upon cell activation. In contrast to the membrane form of CD83, soluble CD83 appears to be immunosuppressive. In an analysis of the phenotype of leukemic CD4(+) T cells from patients with adult T-cell leukemia (ATL), we found that a number of primary CD4(+) T cells became positive for cell surface CD83 after short-term culture, and that most of these CD83(+) CD4(+) T cells were positive for human T-cell leukemia virus type-I (HTLV-I) Tax (Tax1). We hypothesized that Tax1 is involved in the induction of CD83. Result: We found that CD83 was expressed selectively on Tax1-expressing human CD4(+) T cells in short-term cultured peripheral blood mononuclear cells (PBMCs) isolated from HTLV-I+ donors, including ATL patients and HTLV-I carriers. HTLV-I-infected T cell lines expressing Tax1 also expressed cell surface CD83 and released soluble CD83. CD83 can be expressed in the JPX-9 cell line by cadmium-mediated Tax1 induction and in Jurkat cells or PBMCs by Tax1 introduction via infection with a recombinant adenovirus carrying the Tax1 gene. The CD83 promoter was activated by Tax1 in an NF-kappa B-dependent manner. Based on a previous report showing soluble CD83-mediated prostaglandin E2 (PGE2) production from human monocytes in vitro, we tested if PGE2 affected HTLV-I propagation, and found that PGE2 strongly stimulated expression of Tax1 and viral structural molecules. Conclusions: Our results suggest that HTLV-I induces CD83 expression on T cells via Tax1 -mediated NF-kappa B activation, which may promote HTLV-I infection in vivo.

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Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group

H. Itonaga, Y. Sawayama, J. Taguchi, S. Honda, H. Taniguchi, J. Makiyama, E. Matsuo, S. Sato, K. Ando, D. Imanishi, Y. Imaizumi, S. Yoshida, T. Hata, Y. Moriuchi, T. Fukushima, Y. Miyazaki

BONE MARROW TRANSPLANTATION ( NATURE PUBLISHING GROUP )  50 ( 4 ) 585 - 591   2015.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P&lt;0.001). Furthermore, relapse with a new lesion only in the absence of the primary lesion was more frequent in allo-SCT (P = 0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P = 0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.

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The intractable intra-abdominal hemorrhage with unknown etiology in a patient with severe hemophilia A.

Morichika K, Tomoyose T, Nishi Y, Nakachi S, Fukushima T, Masuzaki H

The American journal of emergency medicine ( W B SAUNDERS CO-ELSEVIER INC )  33 ( 1 ) 129.e1 - 3   2015.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Severe hemophilia patients are more likely to be complicated by intra-articular hemorrhage, subcutaneous hemorrhage, and intra-mascular hemorrhage. Spontaneous intra-abdominal hemorrhage is a rare fatal disease, which is an arterial bleeding of uncertain causes from vessel feeding arteries. In case the spontaneous intra-abdominal hemorrhage is complicated to severe hemophilia patients, the mortality rate increases considerably. We experienced a patient with severe hemophilia A, who made a full recovery from spontaneous intra-abdominal hemorrhagic shock by replacement therapy of coagulation factor VII, a noninvasive procedure.

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Giant Septic Lymphadenitis with Marked Gas Formation Caused by Bacteroides fragilis in a Patient with Adult T-cell Leukemia/lymphoma.

Tomoyose T, Nakachi S, Nishi Y, Morichika K, Tedokon I, Tamaki K, Shimabukuro N, Hanashiro T, Samura H, Fukushima T, Masuzaki H

Internal medicine (Tokyo, Japan) ( 一般社団法人 日本内科学会 )  54 ( 22 ) 2919 - 22   2015 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Adult T-cell leukemia/lymphoma (ATL) sometimes causes opportunistic infections. A 53-year-old woman with systemic lymphadenopathies was diagnosed with ATL by inguinal lymph node biopsies and underwent oral chemotherapy. Two months later, high grade fever, lower abdominal pain and lymphadenopathy recurred. Computed tomography revealed the presence of lymphadenopathy with marked gas formation in the pelvic lesion. Blood cultures were suggestive of septic lymphadenitis by <i>Bacteroides fragilis</i> (<i>BF</i>). This represents the first demonstration of giant lymphadenitis with gas formation caused by <i>BF</i> in a patient with ATL. Notably, septic lymphadenitis is pivotal in the differential diagnosis of systemic lymphadenopathy in ATL.<br>

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Successful treatment of a chronic-phase T-315-mutated chronic myelogenous leukemia patients with a combination of imatinib and interferon-alfa.

Itonaga H, Tsushima H, Hata T, Matsuo E, Imanishi D, Imaizumi Y, Kawaguchi Y, Fukushima T, Doi Y, Mori S, Kamihira S, Tomonaga M, Miyazaki Y.

Int J Hematol ( その他の出版社 )  95   209 - 213   2012 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

High expression of 67-kDa laminin receptor relates to the proliferation of leukemia cells and increases expression of GM-CSF receptor.

Ando K, Miyazaki Y, Sawayama Y, Tominaga S, Matuso E, Yamasaki R, Inoue Y, Iwanaga M, Imanishi D, Tsushima H, Fukushima T, Imaizumi Y, Taguchi J, Yoshida S, Hata T, Tomonaga M.

Exp Heamtol ( その他の出版社 )  39   179 - 186   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Allogeneic hematopoietic stem cell transplantation for ATL with central nervous system involvement: The Nagasaki Transplant Group experience.

Fukushima T, Taguchi J, Moriuchi Y, Yoshida S, Itonaga H, Ando K, Sawayama Y, Imaizumi Y, Imanishi D, Hata T, Miyazaki Y.

Int J Hematol ( その他の出版社 )  94   390 - 394   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: durable CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts.

Tominaga-Sato S, Tsushima H, Ando K, Itonaga H, Imaizumi Y, Imanishi D, Iwanaga M, Taguchi J, Fukushima T, Yoshida S, Hata T, Moriuchi Y, Kuriyama K, Mano H, Tomonaga M, Miyazaki Y.

Int J Hematol ( その他の出版社 )  94   81 - 89   2011 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Is zidovudine and interferon-alfa the gold standard for adult T-cell leukemia-lymphoma?

Ishitsuka K, Fukushima T, Tsukasaki K, Tobinai K.

J Clin Oncol ( その他の出版社 )  28   e765   2010 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors.

Iwanaga M, Tagawa M, Tsukasaki K, Matsuo T, Yokota K, Miyazaki Y, Fukushima T, Hata T, Imaizumi Y, Imanishi D, Taguchi J, Momita S, Kamihira S, Tomonaga M.

Blood ( その他の出版社 )  113   1639 - 1650   2009 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Long-term efficacy of imatinib in a practical setting is correlated with imatinib trough concentration that is influenced by body size: a report by the Nagasaki CML Study Group.

Sakai M, Miyazaki Y, Matsuo E, Moriuchi Y, Hata T, Fukushima T, Imaizumi Y, Imanishi D, Taguchi J, Iwanaga M, Tsushima H, Inoue Y, Takasaki Y, Tsuchiya T, Komoda M, Ando K, Horio K, Moriwaki Y, Tominaga S, Itonaga H, Nagai K, Tsukasaki K, Tsutsumi C, Sawayama Y, Yamasaki R, Ogawa D, Kawaguchi Y, Ikeda S, Yoshida S, Onimaru Y, Tawara M, Atogami S, Koida S, Joh T, Yamamura M, Matsuo Y, Soda H, Nonaka H, Jinnai I, Kuriyama K, Tomonaga M.

Int J Hematol ( その他の出版社 )  89   319 - 325   2009 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Expression of myeloperoxidase enhances the chemosensitivity of leukemia cells through the generation of reactive oxygen species and the nitration of protein.

Sawayama Y, Miyazaki Y, Ando K, Horio K, Tsutsumi C, Imanishi D, Tsushima H, Imaizumi Y, Hata T, Fukushima T, Yoshida S, Onimaru Y, Iwanaga M, Taguchi J, Kuriyama K, Tomonaga M.

Leukemia ( その他の出版社 )  22   956 - 964   2008 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Successful cord blood transplantation for mycosis fungoides.

Fukushima T, Horio K, Matsuo E, Imanishi D, Yamasaki R, Tsushima H, Imaizumi Y, Ohshima K, Hata T, Yoshida S, Miyazaki Y, Tomonaga M.

Int J Hematol ( その他の出版社 )  88   596 - 598   2008 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Imatinib provides durable molecular and cytogenetic responses in a practical setting for both newly diagnosed and previously treated chronic myelogenous leukemia: a study in Nagasaki prefecture, Japan.

Matsuo E, Miyazaki Y, Tsutsumi C, Inoue Y, Yamasaki R, Hata T, Fukushima T, Tsushima H, Imanishi D, Imaizumi Y, Iwanaga M, Sakai M, Ando K, Sawayama Y, Ogawa D, Kawaguchi Y, Nagai K, Tsukasaki K, Ikeda S, Moriuchi Y, Yoshida S, Honda M, Taguchi J, Onimaru Y, Tsuchiya T, Tawara M, Atogami S, Yamamura M, Soda H, Yoshida Y, Matsuo Y, Nonaka H, Joh T, Takasaki Y, Kawasaki C, Momita S, Jinnai I, Kuriyama K, Tomonaga M.

Int J Hematol ( その他の出版社 )  85   132 - 139   2007 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Primary T-cell lymphoma of the thyroid gland with chemokine receptors of Th1 phenotype complicating autoimmune thyroiditis.

Koida S, Tsukasaki K, Tsuchiya T, Harasawa H, Fukushima T, Yamada Y, Ohshima K, Kamihira S, Kikuchi M, Tomonaga M.

Haematologica ( その他の出版社 )  92   e37-40   2007 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Japan Clinical Oncology Group Study JCOG9801. VCAP-AMP- VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801.

Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M

J Clin Oncol ( その他の出版社 )  25   5458 - 5464   2007 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants.

Imanishi D, Miyazaki Y, Yamasaki R, Sawayama Y, Taguchi J, Tsushima H, Fukushima T, Yoshida S, Sasaki H, Hata T, Tomonaga M

Blood ( その他の出版社 )  110   2231 - 2234   2007 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Small number of HTLV-1-positive cells frequently remains during complete remission after allogeneic hematopoietic stem cell transplantation that are heterogeneous in origin among cases with adult T-cell leukemia/lymphoma.

Yamasaki R, Miyazaki Y, Moriuchi Y, Tsutsumi C, Fukushima T, Yoshida S, Taguchi J, Inoue Y, Matsuo E, Imaizumi Y, Imanishi D, Fujimoto T, Tsushima H, Honda S, Hata T, Tsukasaki K, Tomonaga M.

Leukemia ( その他の出版社 )  21   1212 - 1217   2007 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates to the prognosis of acute myeloid leukemia.

Taguchi J, Miyazaki Y, Tsutsumi C, Sawayama Y, Ando K, Tsushima H, Fukushima T, Hata T, Yoshida S, Kuriyama K, Honda S, Jinnai I, Mano H, Tomonaga M.

Leuk Res ( その他の出版社 )  30   1105 - 1112   2006 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

A novel plasmacytoid dendritic cell line, CAL-1, established from a patient with blastic natural killer cell lymphoma.

Maeda T, Murata K, Fukushima T, Sugahara K, Tsuruda K, Anami M, Onimaru Y, Tsukasaki K, Tomonaga M, Moriuchi R, Hasegawa H, Yamada Y, Kamihira S.

Int J Hematol ( その他の出版社 )  81   148 - 154   2005 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma.

Fukushima T, Miyazaki Y, Honda S, Kawano F, Moriuchi Y, Masuda M, Tanosaki R, Utsunomiya A, Uike N, Yoshida S, Okamura J, Tomonaga M.

Leukemia ( その他の出版社 )  19   829 - 834   2005 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Membranous nephropathy after allogeneic stem cell transplantation: report of 2 cases.

Tsutsumi C, Miyazaki Y, Fukushima T, Yashida S, Taguchi J, Miyake C, Miyazaki M, Kohno S, Jinnai I, Tomonaga M.

Int J Hematol ( その他の出版社 )  79   193 - 197   2004 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases.

Fukushima T, Miyazaki Y, Tsushima H, Tsutsumi C, Taguchi J, Yoshida S, Kuriyama K, Scadden D, Nimer S, Tomonaga M.

Leuk Res ( その他の出版社 )  27   387 - 392   2003 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Pure red cell aplasia associated with parvovirus B19 infection in a patient with ulcerative colitis.

Isomoto H, Fukuda Y, Bando Y, Machida I, Machida H, Omagari K, Mizuta Y, Murase K, Fukushima T, Murata I, Kohno S.

Dig Dis Sci ( その他の出版社 )  48   2104 - 2107   2003 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Peripheral T-cell lymphoma with a nodular growth pattern.

Hatano B, Fukushima T, Honda M, Hayashi T, Tsuda N, Ohshima K, Tsuchiya T, Kikuchi M.

Pathol Int ( その他の出版社 )  52   400 - 405   2002 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy.

Yoshida S, Kuriyama K, Miyazaki Y, Taguchi J, Fukushima T, Honda M, Hayashibara T, Nagai K, Atogami S, Toriya K, Soda H, Nonaka H, Momita S, Jinnai I, Amenomori T, Kusano M, Yoshida Y, Ikeda S, Matsuo T, Tomonaga M.

Leuk Res ( その他の出版社 )  25   33 - 38   2001 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Allogeneic bone marrow transplantation improves the outcome of de novo AML with trilineage dysplasia (AML-TLD).

Taguchi J, Miyazaki Y, Yoshida S, Fukushima T, Moriuchi Y, Jinnai I, Matsuo T, Kuriyama K, Tomonaga M.

Leukemia ( その他の出版社 )  14   1861 - 1866   2000 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV-I genotype.

Tsukasaki K, Imaizumi Y, Tawara M, Fujimoto T, Fukushima T, Hata T, Maeda T, Yamada Y, Kamihira S, Tomonaga M.

Br J Haematol ( その他の出版社 )  105   369 - 375   1999 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

oor outcome of autologous stem cell transplantation for adult T cell leukemia/lymphoma: a case report and review of the literature.

Tsukasaki K, Maeda T, Arimura K, Taguchi J, Fukushima T, Miyazaki Y, Moriuchi Y, Kuriyama K, Yamada Y, Tomonaga M.

Bone Marrow 　Transplant ( その他の出版社 )  23   87 - 89   1999 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Successful bone marrow transplantation for idiopathic hypereosinophilic syndrome.

Fukushima T, Kuriyama K, Ito H, Miyazaki Y, Arimura K, Hata T, Saitoh M, Tomonaga M.

Br J Haematol ( その他の出版社 )  90   213 - 215   1995 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

Unusual morphological features of adult T-cell leukemia cells with aberrant immunophenotype.

Kamihira S, Sohda H, Atogami S, Fukushima T, Toriya K, Miyazaki Y, Ikeda S, Yamada Y, Tomonaga M.

Leuk Lymphoma ( その他の出版社 )  12   123 - 130   1993 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)