Published Papers - Fukushima Takuya

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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