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Giang Huong Nguyen, James Y Wang, Kenneth B Hymes, Cynthia M Magro
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities...
October 12, 2016: American Journal of Dermatopathology
Junki Kato, Ayako Masaki, Keiichiro Fujii, Hisashi Takino, Takayuki Murase, Kentaro Yonekura, Atae Utsunomiya, Takashi Ishida, Shinsuke Iida, Hiroshi Inagaki
Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non-quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T-cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers...
September 27, 2016: Pathology International
Takashi Ishida, Hiroshi Fujiwara, Kisato Nosaka, Naoya Taira, Yasunobu Abe, Yoshitaka Imaizumi, Yukiyoshi Moriuchi, Tatsuro Jo, Kenichi Ishizawa, Kensei Tobinai, Kunihiro Tsukasaki, Shigeki Ito, Makoto Yoshimitsu, Maki Otsuka, Michinori Ogura, Shuichi Midorikawa, Wanda Ruiz, Tomoko Ohtsu
PURPOSE: Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. PATIENTS AND METHODS: Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible...
September 12, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yukie Tsubokura, Atsushi Satake, Masaaki Hotta, Hideaki Yoshimura, Shinya Fujita, Yoshiko Azuma, Takahisa Nakanishi, Aya Nakaya, Tomoki Ito, Kazuyoshi Ishii, Shosaku Nomura
A humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab (MOG), has been shown to be safe and effective in the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL). MOG depletes ATLL cells as well as regulatory T cells (Tregs), as CCR4 is expressed on these cells as well. In this context, pretransplant treatment with MOG may induce severe graft-versus-host disease (GVHD) in allogeneic hematopoietic stem-cell transplantation (HSCT). However, the influence of MOG on allogeneic HSCT, including its induction of GVHD, is unclear...
August 29, 2016: International Journal of Hematology
Horlad Hasita, Chaoya Ma, Hiromu Yano, Cheng Pan, Koji Ohnishi, Yukio Fujiwara, Shinya Endo, Yoshitaka Kikukawa, Yutaka Okuno, Masao Matsuoka, Motohiro Takeya, Yoshihiro Komohara
Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domain-containing molecule-3. In the present study, we investigated expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin embedded tissue samples, and subsequently studied the detailed mechanism of up-regulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines...
August 26, 2016: Cancer Science
Hiromi Nagano, Yuichi Kurono, Kakushi Matushita
OBJECTIVE: One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV-1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients. METHODS: The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013...
August 20, 2016: Auris, Nasus, Larynx
Christa Roe, Rami Komrokji, Ling Zhang, Samantha Price, Lubomir Sokol
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is aggressive mature T-cell lymphoproliferative disorder with a poor outcome. METHODS: We present 10 patients with acute and lymphomatous subtypes of ATLL treated with distinct induction regimens, including CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], prednisone or prednisolone), interferon/zidovudine, and VCAP-AMP-VECP (vincristine, cyclophosphamide, doxorubicin, prednisone; doxorubicin, ranimustine, prednisone; vindesine, etoposide, carboplatin, prednisone)...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken-Ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Hasita Horlad, Koji Ohnishi, Chaoya Ma, Yukio Fujiwara, Daisuke Niino, Koichi Ohshima, Masahisa Jinushi, Masao Matsuoka, Motohiro Takeya, Yoshihiro Komohara
Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples...
August 2016: Oncology Letters
Hiroaki Miyoshi, Junichi Kiyasu, Takeharu Kato, Noriaki Yoshida, Joji Shimono, Shintaro Yokoyama, Hiroaki Taniguchi, Yuya Sasaki, Daisuke Kurita, Keisuke Kawamoto, Koji Kato, Yoshitaka Imaizumi, Masao Seto, Koichi Ohshima
Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7...
September 8, 2016: Blood
Hisayoshi Kondo, Midori Soda, Norie Sawada, Manami Inoue, Yoshitaka Imaizumi, Yasushi Miyazaki, Masako Iwanaga, Yasuhito Tanaka, Masashi Mizokami, Shoichiro Tsugane
BACKGROUND AND PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1); no effective methods have yet been identified to prevent development of ATLL in carriers of HTLV-1. This study investigated the association between cigarette smoking and the risk of ATLL development among Japanese carriers of HTLV-1. METHODS: This study examined the association between smoking and development of ATLL in a cohort of 1,332 Japanese HTLV-1 carriers aged 40-69 years free of ATLL at baseline from two different HTLV-1-endemic areas of Japan...
September 2016: Cancer Causes & Control: CCC
Sakura Aoki, Sanaz Firouzi, Yosvany López, Tadanori Yamochi, Kazumi Nakano, Kaoru Uchimaru, Atae Utusnomiya, Masako Iwanaga, Toshiki Watanabe
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the transformation of HTLV-1-infected T cells. ATLL, especially its aggressive form, is known for its poor prognosis, even with intensive chemotherapy. ATLL cells are considered to be monoclonal; however, multiclonal proliferation or emergence of a new clone over time has been reported based on Southern blot analysis, although direct molecular evidence remains elusive. Furthermore, it is thought that clonal change may be a cause of early drug resistance in ATLL...
September 2016: International Journal of Hematology
Takahiro Shima, Kenjiro Kamezaki, Kazuhiko Higashioka, Shuichiro Takashima, Goichi Yoshimoto, Koji Kato, Tsuyoshi Muta, Katsuto Takenaka, Hiromi Iwasaki, Toshihiro Miyamoto, Koichi Akashi
A 74-year-old woman with refractory adult T-cell leukemia/lymphoma (ATLL) received three courses of mogamulizumab. Despite obtaining complete remission, she thereafter presented with progressive ascites. An analysis of the ascites and laboratory tests revealed no evidence of ATLL invasion, infectious disease, or liver cirrhosis. The mogamulizumab concentrations were maintained in the ascites at approximately 10-15% of that in the plasma. Mogamulizumab was considered to be a plausible pathogenesis of her ascites...
2016: Internal Medicine
Chie Ishikawa, Masachika Senba, Naoki Mori
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATLL is associated with poor prognosis mainly due to resistance to chemotherapy, which highlights the requirement for alternative therapies. The chaperone heat shock protein (HSP) 90 assist proteins involved in the onset and progression of ATLL. In the present study, the efficacy of a second generation HSP90 inhibitor termed AUY922 was investigated in ATLL. In vitro, AUY922 induced marked inhibition of cell viability in the HTLV-1-infected T-cell lines HUT-102 and MT-4...
July 2016: Oncology Letters
Monica Zell, Amer Assal, Olga Derman, Noah Kornblum, Ramakrishna Battini, Yanhua Wang, Deepa M Narasimhulu, Ioannis Mantzaris, Aditi Shastri, Amit Verma, Hilda Ye, Ira Braunschweig, Murali Janakiram
Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive disease caused by human T-cell lymphotropic virus type 1 that predominantly affects Japanese and Caribbean populations. Most studies have focused on Japanese cohorts. We conducted a retrospective analysis of 53 cases of ATLL who presented to our institution between 2003-2014. ATLL in the Caribbean population presents more often as the acute and lymphomatous subtypes, is associated with complex cytogenetics, and has a high rate of CNS involvement...
June 22, 2016: Oncotarget
Kazumi Nakano, Kaoru Uchimaru, Atae Utsunomiya, Kazunari Yamaguchi, Toshiki Watanabe
PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive human T-cell malignancy induced by human T-lymphotrophic virus-1 (HTLV-1) infection. The genetic alterations in infected cells that lead to transformation have not been completely elucidated, thus hindering the identification of effective therapeutic targets for ATL. Here, we present the first assessment of MYB proto-oncogene dysregulation in ATL and an exploration of its role in the onset of ATL. EXPERIMENTAL DESIGN: We investigated the expression patterns of MYB splicing variants in ATL...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
T Ohsugi, M Wakamiya, S Morikawa, M Fujita
Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL). The Tax protein encoded by the pX region of the HTLV-1 genome appears to be a key element in the early stage of ATLL development. In this study, we examined the expression of the downstream of tyrosine kinase (DOK) family members DOK1, DOK2 and DOK3, recently reported to be tumor suppressors, in HTLV-1-transformed T cells (MT-2 and HUT-102) and TL-Om1 cells derived from ATLL leukemic cells...
June 2016: Acta Virologica
Ariella L G Coler-Reilly, Naoko Yagishita, Hiroko Suzuki, Tomoo Sato, Natsumi Araya, Eisuke Inoue, Ayako Takata, Yoshihisa Yamano
BACKGROUND: At least one million people are infected with human T-lymphotropic virus type 1 (HTLV-1) in Japan, a small percentage of whom develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Patients with HAM/TSP suffer from progressively worsening myelopathic symptoms, such as motor disability and bladder dysfunction, and may become wheelchair-bound or even bedridden. METHODS: To learn more about this rare, debilitating disease, we established the national registration system "HAM-net" in March 2012...
2016: Orphanet Journal of Rare Diseases
Takeshi Sugio, Koji Kato, Takatoshi Aoki, Takanori Ohta, Noriyuki Saito, Shuro Yoshida, Ichiro Kawano, Hideho Henzan, Masanori Kadowaki, Ken Takase, Tsuyoshi Muta, Kohta Miyawaki, Takuji Yamauchi, Takahiro Shima, Shuichiro Takashima, Yasuo Mori, Goichi Yoshimoto, Kenjiro Kamezaki, Katsuto Takenaka, Hiromi Iwasaki, Ryosuke Ogawa, Yuju Ohno, Tetsuya Eto, Tomohiko Kamimura, Toshihiro Miyamoto, Koichi Akashi
Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT...
September 2016: Biology of Blood and Marrow Transplantation
Takuro Kuriyama, Noriaki Kawano, Kiyoshi Yamashita, Ikuo Kikuchi
Primary bone lymphomas comprise <1 % of all malignant lymphomas, and there have been only a limited number of reports on primary adult T-cell leukemia/lymphoma (ATLL) of bone. Here, we report two cases of primary ATLL of bone. The first case was a 41-year-old woman with multiple bone tumors. She was diagnosed with ATLL of the skull through biopsy and treated with chemotherapy. Although the bone lesions showed transient improvement, the subsequent central nervous system (CNS) invasion of ATLL occurred and she died 7 months after diagnosis...
September 2016: International Journal of Hematology
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