53 results on '"Ennishi, Daisuke"'
Search Results
2. Recent updates on treatment options for primary follicular lymphoma of the gastrointestinal tract.
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Iwamuro, Masaya, Tanaka, Takehiro, Ennishi, Daisuke, and Otsuka, Motoyuki
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FOLLICULAR lymphoma ,BOWEL obstructions ,GASTROINTESTINAL system ,INTESTINAL tumors ,LYMPHOMAS - Abstract
Background: Primary gastrointestinal follicular lymphoma is a subtype of follicular lymphoma that originates directly from the gastrointestinal tract. Pathologically, it exhibits substantial similarities with the secondary gastrointestinal involvement observed in nodal follicular lymphoma. However, primary gastrointestinal follicular lymphoma presents clinically distinct features, necessitating divergent considerations in treatment selection compared with nodal follicular lymphoma. Areas covered: This narrative review focused on recent articles (2018–2023) regarding the long-term prognosis and treatment options for gastrointestinal follicular lymphoma. In addition, a brief overview of gastrointestinal follicular lymphomas is provided. Expert opinion: Patients with primary gastrointestinal follicular lymphoma often present with a low tumor burden. Lymphoma lesions typically remain asymptomatic for several years or may undergo spontaneous regression without immediate treatment. Therefore, a 'watch and wait' approach is justified. Conversely, when large tumor masses are identified in the gastrointestinal tract, the potential for tumor bleeding or intestinal obstruction requires timely therapeutic interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation.
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Iwamuro, Masaya, Ennishi, Daisuke, Fujii, Nobuharu, Matsuoka, Ken-ichi, Tanaka, Takehiro, Inokuchi, Toshihiro, Hiraoka, Sakiko, and Otsuka, Motoyuki
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STEM cell transplantation ,GASTROINTESTINAL mucosa ,IRRITABLE colon ,SHORT bowel syndrome ,INTESTINES ,APPETITE loss ,GASTROINTESTINAL system - Abstract
Background: Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM. Methods: This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated. Results: The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52–247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%. Conclusions: This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Collection efficiency and safety of large‐volume leukapheresis for the manufacturing of tisagenlecleucel.
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Kitamura, Wataru, Urata, Tomohiro, Fujii, Keiko, Fukumi, Takuya, Ikeuchi, Kazuhiro, Seike, Keisuke, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Matsuoka, Ken‐ichi, Otsuka, Fumio, Maeda, Yoshinobu, and Fujii, Nobuharu
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LEUKAPHERESIS ,B cell lymphoma ,BLOOD volume ,CD3 antigen - Abstract
Background: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non‐Hodgkin lymphoma (r/r B‐ALL/B‐NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal‐volume leukapheresis (NVL). Large‐volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa‐cel) remain unclear. This study aimed to investigate the tolerability of LVL. Study Design and Methods: We retrospectively collected data on LVL (≥3‐fold TBV) and NVL (<3‐fold TBV) performed for patients with r/r B‐ALL/B‐NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. Results: Although pre‐apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p <.01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out‐of‐specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p =.43) and no patient discontinued leukapheresis due to any complications. Conclusion: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa‐cel. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma.
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Hayashino, Kenta, Seike, Keisuke, Fujiwara, Kanako, Kondo, Kaho, Matsubara, Chisato, Terao, Toshiki, Kitamura, Wataru, Kamoi, Chihiro, Fujiwara, Hideaki, Asada, Noboru, Nishimori, Hisakazu, Ennishi, Daisuke, Fujii, Keiko, Fujii, Nobuharu, Matsuoka, Ken-ichi, and Maeda, Yoshinobu
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Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab−Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab−Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Japanese phase Ib study of the oral PI3K-δ and -γ inhibitor duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
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Makita, Shinichi, Ota, Shuichi, Mishima, Yuko, Usuki, Kensuke, Ennishi, Daisuke, Yanada, Masamitsu, Fukuhara, Noriko, Yamamoto, Ryusuke, Takamine, Atsushi, Nohara, Go, and Izutsu, Koji
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This phase Ib, open-label, single-arm, multicenter study assessed the efficacy and safety of duvelisib, an oral dual inhibitor of phosphatidylinositol 3-kinase-δ and -γ, in Japanese patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Duvelisib was administered orally at 25 mg twice a day (BID) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and all responses were assessed by an independent review committee. Nine CLL patients and 1 SLL patient were enrolled. ORR was 80% (95% confidence interval 44.4, 97.5) for all 10 patients. All 6 patients previously treated with a Bruton's tyrosine kinase (BTK) or BCL2 inhibitor achieved a partial response. The most common adverse events were neutropenia (50%), diarrhea (40%), anemia, hypokalemia, constipation and rash (30% each). The most common grade ≥ 3 adverse events were neutropenia (50%), anemia (30%) and thrombocytopenia (20%). Duvelisib 25 mg BID showed favorable efficacy and a manageable safety profile in selected Japanese patients with r/r CLL/SLL, including patients previously treated with BTK or BCL2 inhibitors (Clinical trial registration: jRCTs2080224791). [ABSTRACT FROM AUTHOR]
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- 2024
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7. A Learning Program for Treatment Recommendations by Molecular Tumor Boards and Artificial Intelligence.
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Sunami, Kuniko, Naito, Yoichi, Saigusa, Yusuke, Amano, Toraji, Ennishi, Daisuke, Imai, Mitsuho, Kage, Hidenori, Kanai, Masashi, Kenmotsu, Hirotsugu, Komine, Keigo, Koyama, Takafumi, Maeda, Takahiro, Morita, Sachi, Sakai, Daisuke, Hirata, Makoto, Ito, Mamoru, Kozuki, Toshiyuki, Sakashita, Hiroyuki, Horinouchi, Hidehito, and Okuma, Yusuke
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- 2024
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8. Evaluating the efficiency and safety of large‐volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study.
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Sumii, Yuichi, Fujii, Keiko, Kondo, Takumi, Urata, Tomohiro, Kimura, Maiko, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Otsuka, Fumio, Maeda, Yoshinobu, and Fujii, Nobuharu
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STEM cells ,BLOOD cells ,STEM cell transplantation ,BLOOD volume ,BLOOD platelets ,LEUKAPHERESIS ,CD34 antigen - Abstract
Background: Large‐volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. Study Design and Methods: We retrospectively collected data on LVL (>3 total blood volume) and normal‐volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. Results: Although pre‐apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/μL, p <.001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p =.966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p <.001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p =.322). All LVL procedures could be completed without any adverse events. Conclusion: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Long non‐coding RNAs associated with transcriptomic signatures and treatment outcome in diffuse large B‐cell lymphoma.
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Duns, Gerben, Winkle, Melanie, Chong, Lauren, Ennishi, Daisuke, Morin, Ryan D., Diepstra, Arjan, Scott, David W., Kluiver, Joost L., Steidl, Christian, and van den Berg, Anke
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LINCRNA ,GENE expression ,DIFFUSE large B-cell lymphomas ,TREATMENT effectiveness ,TRANSCRIPTOMES - Abstract
Long non-coding RNAs associated with transcriptomic signatures and treatment outcome in diffuse large B-cell lymphoma I PVT1 i transcript levels might represent a promising marker for poor prognosis in this subset of DLBCL, but whether overexpression of I PVT1 i actively contributes to an aggressive clinical phenotype in these MYC-dysregulated tumours remains to be elucidated. I PVT1 i transcript levels are on average higher in I MYC i -translocated samples and DZsig-pos cases compared with other GCB-DLBCLs (Figure 2B), and do not show a significant correlation with I MYC i transcript levels in GCB-DLBCL, regardless of I MYC i translocation or DZsig status (Figure S9). To identify COO-specific associations we restricted the univariate COX regression analysis to ABC-DLBCL or GCB-DLBCL samples. [Extracted from the article]
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- 2023
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10. Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy.
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Kitamura, Wataru, Asada, Noboru, Naoi, Yusuke, Abe, Masaya, Fujiwara, Hideaki, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Matsuoka, Ken‐ichi, Yoshino, Tadashi, and Maeda, Yoshinobu
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BONE marrow ,DIFFUSE large B-cell lymphomas ,T cells ,STEM cell factor ,CHIMERIC antigen receptors - Abstract
Summary: Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T‐cell therapy, an emerging therapy for relapsed or refractory diffuse large B‐cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T‐cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T‐cell infusion in patients with PC. Cytokine analyses after CAR T‐cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation‐related cytokines on day 28 after CAR T‐cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation‐related cytokines in the BM following CAR T‐cell infusion are associated with subsequent PC. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch.
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Kondo, Takumi, Fujii, Keiko, Fujii, Nobuharu, Sumii, Yuichi, Urata, Tomohiro, Kimura, Maiko, Matsuda, Masayuki, Ikegawa, Shuntaro, Washio, Kana, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Otsuka, Fumio, and Maeda, Yoshinobu
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HYDROXYETHYL starch ,MOLECULAR weights ,HEMAPHERESIS ,ERYTHROCYTES ,HEMODILUTION ,BLOOD transfusion ,COLLECTIONS - Abstract
Background: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. Study Design and Methods: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. Results: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. Conclusion: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Long-term outcomes of patients with primary intestinal follicular lymphoma managed with watch-and-wait strategy.
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Iwamuro, Masaya, Tanaka, Takehiro, Ennishi, Daisuke, Matsueda, Kazuhiro, Yoshioka, Masao, Miyahara, Koji, Sakaguchi, Chihiro, Nishimura, Mamoru, Nagahara, Teruya, Mannami, Tomohiko, Takenaka, Ryuta, Oka, Shohei, Inoue, Masafumi, Takimoto, Hidetaka, Inaba, Tomoki, Kobayashi, Sayo, Toyokawa, Tatsuya, Tsugeno, Hirofumi, Suzuki, Seiyuu, and Sawada, Sachiko
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FOLLICULAR lymphoma ,INTESTINES ,SURVIVAL rate ,OVERALL survival ,DISEASE progression - Abstract
Patients with primary intestinal follicular lymphoma are often followed-up without a specific treatment, and this approach is called the "watch-and-wait approach." However, the long-term outcomes of this patient group have not been sufficiently investigated. We enrolled patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression. Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II
1 ). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%. In conclusion, an indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients. [ABSTRACT FROM AUTHOR]- Published
- 2023
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13. Association between early corticosteroid administration and long-term survival in non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation.
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Kambara, Yui, Fujii, Nobuharu, Usui, Yoshiaki, Yamamoto, Akira, Higo, Hisao, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Matsuoka, Ken-ichi, and Maeda, Yoshinobu
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Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period. Thirty-seven were diagnosed with NIPCs, which consisted of idiopathic pneumonia syndrome, bronchiolitis obliterans, and interstitial lung disease including cryptogenic organizing pneumonia. Among these, 18 died (Dead group) while 19 remained alive (Alive group) during the study period. The median time between NIPC diagnosis and first administration of ≥ 1 mg/kg/day corticosteroids (prednisolone dose equivalent) was significantly longer in the Dead group than the Alive group, at 9 days versus 4 days (p = 0.01). We further divided these cases into those who received prednisolone within seven days and after 8 days. We found that the ≤ 7 days group were more likely to survive after their NIPC diagnosis compared to the ≥ 8 days group (p = 0.06). Our analysis showed that early initiation of corticosteroid therapy is associated with long-term survival in NIPCs. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Biological and clinical significance of epigenetic alterations in B-cell lymphomas.
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Ennishi, Daisuke
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Recent advances in genetic analysis of hematopoietic tumors have led to the discovery of enzyme abnormalities that control epigenetic changes. Notably, genetic mutations associated with DNA methylation and histone modifications have been identified in B-cell malignant lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma. Gene expression involved in B lymphocyte differentiation and maturation within the germinal center (GC) is regulated epigenetically in these lymphomas, and epigenetic alterations play critical roles in the pathogenesis of GC-driven lymphomas. Recent studies also indicate the importance of epigenetic alterations as biomarkers and therapeutic targets, suggesting that they will have a central role in developing precision medicine for patients with GC-driven lymphomas. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma: an open-label, multicenter, dose-escalation phase 1 study.
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Goto, Hideki, Izutsu, Koji, Ennishi, Daisuke, Mishima, Yuko, Makita, Shinichi, Kato, Koji, Hanaya, Miyoko, Hirano, Satoshi, Narushima, Kazuya, Teshima, Takanori, Nagai, Hirokazu, and Ishizawa, Kenichi
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The selective phosphatidylinositol 3-kinase δ inhibitor zandelisib demonstrated favorable safety and efficacy [objective response rate (ORR) 79%] in patients with B-cell malignancies in a phase 1b study in the US and Switzerland. In this phase 1 dose-escalation study (NCT03985189), 9 Japanese patients with relapsed/refractory indolent non-Hodgkin's lymphoma (R/R iNHL) received zandelisib on a continuous daily schedule (45 or 60 mg) until progressive disease/unacceptable toxicity. No dose-limiting toxicities were observed. The maximum tolerated dose was not reached. At a median follow-up of 17.5 months, Grade ≥ 3 treatment-emergent adverse events that occurred in 2 or more patients were neutrophil count decreased (55.6%; 5/9) and diarrhea (33.3%; 3/9). Immune-related toxicities, including hepatobiliary disorder, aspartate/alanine aminotransferase increased, diarrhea/colitis, organizing pneumonia, stomatitis, and rash, led to zandelisib discontinuation in 4 patients. The investigator-assessed ORR, based on modified Lugano criteria, was 100%, including 2 complete responses (22.2%; in follicular lymphoma patients receiving 60 mg/day). Median duration of response, progression-free survival, and time to response were 7.9, 11.1, and 1.9 months, respectively. Zandelisib demonstrated a manageable safety profile at 60 mg, the recommended phase 2 dose (RP2D) in Japanese patients. The RP2D resulted in favorable pharmacokinetics and anti-tumor efficacy in Japanese patients with R/R iNHL. Trial registration. NCT03985189 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]
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- 2022
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16. Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors.
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Imai, Mitsuho, Nakamura, Yoshiaki, Sunami, Kuniko, Kage, Hidenori, Komine, Keigo, Koyama, Takafumi, Amano, Toraji, Ennishi, Daisuke, Kanai, Masashi, Kenmotsu, Hirotsugu, Maeda, Takahiro, Morita, Sachi, Sakai, Daisuke, Bando, Hideaki, Makiyama, Akitaka, Suzuki, Tatsuya, Hirata, Makoto, Kohsaka, Shinji, Tsuchihara, Katsuya, and Naito, Yoichi
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Comprehensive genomic profiling is increasingly used to facilitate precision oncology based on molecular stratification. In addition to conventional tissue comprehensive genomic profiling, comprehensive genomic profiling of circulating tumor DNA has become widely utilized in cancer care owing on its advantages, including less invasiveness, rapid turnaround time, and capturing heterogeneity. However, circulating tumor DNA comprehensive genomic profiling has some limitations, mainly false negatives due to low levels of plasma circulating tumor deoxyribonucleic acid and false positives caused by clonal hematopoiesis. Nevertheless, no guidelines and recommendations fully address these issues. Here, an expert panel committee involving representatives from 12 Designated Core Hospitals for Cancer Genomic Medicine in Japan was organized to develop expert consensus recommendations for the use of circulating tumor deoxyribonucleic acid‐based comprehensive genomic profiling. The aim was to generate guidelines for clinicians and allied healthcare professionals on the optimal use of the circulating tumor DNA assays in advanced solid tumors and to aid the design of future clinical trials that utilize and develop circulating tumor DNA assays to refine precision oncology. Fourteen clinical questions regarding circulating tumor deoxyribonucleic acid comprehensive genomic profiling including the timing of testing and considerations for interpreting results were established by searching and curating associated literatures, and corresponding recommendations were prepared based on the literature for each clinical question. Final consensus recommendations were developed by voting to determine the level of each recommendation by the Committee members. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Chronological improvement in precision oncology implementation in Japan.
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Sunami, Kuniko, Naito, Yoichi, Komine, Keigo, Amano, Toraji, Ennishi, Daisuke, Imai, Mitsuho, Kage, Hidenori, Kanai, Masashi, Kenmotsu, Hirotsugu, Koyama, Takafumi, Maeda, Takahiro, Morita, Sachi, Sakai, Daisuke, Kohsaka, Shinji, Tsuchihara, Katsuya, Saigusa, Yusuke, and Yoshino, Takayuki
- Abstract
In Japan, comprehensive genomic profiling (CGP) tests for refractory cancer patients have been approved since June 2019, under the requirement that all cases undergoing CGP tests are annotated by the molecular tumor board (MTB) at each government‐designated hospital. To investigate improvement in precision oncology, we evaluated and compared the proportion of cases receiving matched treatments according to CGP results and those recommended to receive genetic counseling at all core hospitals between the first period (11 hospitals, June 2019 to January 2020) and second period (12 hospitals, February 2020 to January 2021). A total of 754 and 2294 cases underwent CGP tests at core hospitals in the first and second periods, respectively; 28 (3.7%) and 176 (7.7%) patients received matched treatments (p < 0.001). Additionally, 25 (3.3%) and 237 (10.3%) cases were recommended to receive genetic counseling in the first and second periods, respectively (p < 0.001). The proportion was associated with the type of CGP test: tumor‐only (N = 2391) vs. tumor‐normal paired (N = 657) analysis (10.0% vs. 3.5%). These results suggest that recommendations regarding available clinical trials in networked MTBs might contribute to increasing the numbers of matched treatments, and that tumor‐normal paired rather than tumor‐only tests can increase the efficiency of patient referrals for genetic counseling. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Red blood cell depletion in small-volume bone marrow processing using manipulation with third-party red blood cells: A comparison of the performance of the COBE spectra and the spectra Optia systems.
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Sumii, Yuichi, Fujii, Nobuharu, Fujii, Keiko, Kondo, Takumi, Urata, Tomohiro, Kimura, Maiko, Washio, Kana, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Otsuka, Fumio, Maeda, Yoshinobu, and Matsuoka, Ken-Ichi
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BONE marrow transplantation ,RETROSPECTIVE studies ,IMPACT of Event Scale ,BONE marrow ,ERYTHROCYTES ,ANTIGENS - Abstract
Background: For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia.Study Design and Methods: We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia.Results: The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34+ cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one.Conclusion: The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator. [ABSTRACT FROM AUTHOR]- Published
- 2022
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19. Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia.
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Murakami, Hiroyuki, Matsuoka, Ken-ichi, Asano, Takeru, Moriyama, Takashi, Matsumura, Akifumi, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Toji, Tomohiro, Yoshino, Tadashi, and Maeda, Yoshinobu
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CORD blood transplantation ,ACUTE myeloid leukemia ,VENETOCLAX ,AZACITIDINE ,BLOOD cell count - Abstract
Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment. [ABSTRACT FROM AUTHOR]
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- 2022
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20. Chronic active Epstein–Barr virus infection presenting as refractory chronic sinusitis.
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Kitamura, Wataru, Fujiwara, Hideaki, Matsumura, Akifumi, Higaki, Takaya, Shibata, Rei, Toji, Tomohiro, Fujii, Soichiro, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Matsuoka, Ken-ichi, Yoshino, Tadashi, and Maeda, Yoshinobu
- Abstract
A 44-year-old Japanese man presented with fever and sore throat. He had a history of refractory chronic sinusitis that did not respond to several years of pharmacotherapy, and underwent endoscopic sinus surgery (ESS) 5 months prior to his presentation, but his symptoms persisted. A biopsy specimen was taken from the right nasal cavity, and extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) was diagnosed. Two years after complete remission was achieved by chemoradiation therapy, he developed hemophagocytic lymphohistiocytosis (HLH) without recurrence of ENKTL. Epstein–Barr virus (EBV)-DNA copy number was relatively high and EBV-infected lymphocytes (CD8 + T cells) were detected in the peripheral blood. Pathological review of the biopsy specimens taken during ESS showed that CD8 + T cells with slightly atypia infiltrating the stroma were EBV positive. These findings suggested that the patient had underlying chronic active EBV infection (CAEBV) that caused the refractory chronic sinusitis, eventually developed into ENKTL, and also caused HLH. Clinicians should consider adult-onset CAEBV in the differential diagnosis of patients with refractory chronic sinusitis. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Higher incidence of thrombocytopenia during obinutuzumab plus bendamustine therapy for untreated follicular lymphoma: a retrospective analysis by the Okayama Hematology Study Group.
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Fujiwara, Yuki, Urata, Tomohiro, Niiya, Daigo, Yano, Tomofumi, Nawa, Yuichiro, Yoshida, Isao, Imai, Toshi, Sunami, Kazutaka, Fujii, Soichiro, Ennishi, Daisuke, Maeda, Yoshinobu, and Hiramatsu, Yasushi
- Abstract
Progression-free survival in patients with untreated follicular lymphoma (FL) has significantly improved with obinutuzumab plus chemotherapy followed by obinutuzumab maintenance, compared with rituximab plus chemotherapy. However, the survival outcome and adverse event profile in Japanese FL patients treated with obinutuzumab plus bendamustine (GB) therapy are not well investigated. Recently, we encountered some cases of grade 3-4 thrombocytopenia during GB therapy in patients with FL. This retrospective multicenter survey aimed to identify the characteristics of patients who received GB therapy and developed thrombocytopenia. A total of 54 patients with FL treated by GB therapy between August 2018 and December 2020 were investigated. After a median follow-up of 12.6 months, thrombocytopenia of any grade was observed in 48 (88.9%) patients, including 9 (16.7%) patients with grade 3-4 thrombocytopenia. Notably, although eight of nine patients with grade 3-4 thrombocytopenia were female, no patient characteristics (including gender) were significantly associated with grade 3-4 thrombocytopenia. Importantly, grade 3-4 thrombocytopenia frequently occurred in the first GB therapy cycle, which suggests that platelet count should be monitored carefully in patients who have just started GB therapy. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Low hematocrit reduces the efficiency of CD34+ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure.
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Kondo, Takumi, Fujii, Nobuharu, Fujii, Keiko, Sumii, Yuichi, Urata, Tomohiro, Kimura, Maiko, Matsuda, Masayuki, Ikegawa, Shuntaro, Washio, Kana, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Otsuka, Fumio, and Maeda, Yoshinobu
- Abstract
Background: CD34+ cell collection efficiency (CE) is the determining factor when calculating processed blood volume (PBV) for leukapheresis (LP). However, the factors affecting CE in the continuous mononuclear cell collection (cMNC) protocol performed by the Spectra Optia apheresis system are not well established. Study Design and Methods: We retrospectively collected the data from 147 consecutive apheresis procedures across 106 healthy donors and 27 patients completed between July 2016 and December 2020 at the Okayama University Hospital. All procedures were performed using the Optia cMNC protocol. Results: The median CD34+ CE2 was significantly higher in the donor samples (64.3%) than in the patient samples (46.8%) (p <.0001). WBC counts, hematocrit, and platelet counts were all significantly higher in the donors than in the patients, and there was a moderate positive correlation between CD34+ CE2 and hematocrit (r =.47, p <.0001), with the equation of the line being y = 1.23x + 12.23. In contrast, there was only a very weak correlation between CD34+ CE2 and WBC or platelet count. In addition, low hematocrit correlated with an increased time to interface formation. Conclusion: These data revealed the negative impact of low hematocrit on the efficiency of CD34+ cell collection when using the Optia cMNC protocol and suggest that hematocrit values should also be considered when determining PBV. [ABSTRACT FROM AUTHOR]
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- 2022
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23. Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report.
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Futagawa, Mashu, Yamamoto, Hideki, Kochi, Mariko, Urakawa, Yusaku, Sogawa, Reimi, Kato, Fumino, Okazawa-Sakai, Mika, Ennishi, Daisuke, Shinozaki, Katsunori, Inoue, Hirofumi, Yanai, Hiroyuki, and Hirasawa, Akira
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LEIOMYOSARCOMA ,GERM cells ,BREAST cancer ,WOMEN patients ,UTERINE cancer ,GENETIC counseling - Abstract
Background: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. Case presentation: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. Conclusions: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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24. Transformation to diffuse large B-cell lymphoma with germinal center B-cell like subtype and discordant light chain expression in a patient with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.
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Kobayashi, Hiroki, Asada, Noboru, Egusa, Yuria, Ikeda, Tomoka, Sakamoto, Misa, Abe, Masaya, Ennishi, Daisuke, Sakata, Masahiro, Takaki, Akinobu, Kawahara, Soichiro, Meguri, Yusuke, Nishimori, Hisakazu, Fujii, Nobuharu, Matsuoka, Ken-ichi, Sato, Yasuharu, Yoshino, Tadashi, and Maeda, Yoshinobu
- Abstract
Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare indolent B-cell neoplasm, and a gain-of-function mutation in the myeloid differentiation primary response 88 (MYD88), L265P, is a commonly recurring mutation in patients with WM/LPL. Histological transformation of WM/LPL to an aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL) is rare, and transformed DLBCL has a worse prognosis than de novo DLBCL, partly because transformed DLBCL is mostly classified as non-germinal center B-cell-like (non-GCB) subtype. We herein describe a 75-year-old man with DLBCL with a history of WM/LPL. DLBCL in this patient showed the GCB subtype, and the light chain restriction of DLBCL was different from that of the antecedent WM/LPL, indicating that the two types of lymphoma cells had distinctive origins. However, DLBCL in this patient harbored the MYD88 L265P mutation, and polymerase chain reaction and Sanger sequencing of the DLBCL and WM/LPL for immunoglobulin heavy chain gene rearrangement suggested a clonal relationship between the two lymphomas. Since the outcome of transformed DLBCL is worse than for de novo DLBCL, it is important to evaluate the clonal relationship between primary WM/LPL and the corresponding transformed DLBCL, even if the DLBCL expresses a GCB subtype or discordant light chain restriction. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. Secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs: A case report.
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Taniguchi, Kohei, Yanai, Hiroyuki, Kaji, Tatsuya, Kubo, Toshio, Ennishi, Daisuke, Hirasawa, Akira, and Yoshino, Tadashi
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LYMPHATIC metastasis ,SALIVARY glands ,BREAST ,SWEAT glands ,LUNGS ,SKIN tumors ,CARCINOMA - Abstract
Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31‐year‐old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next‐generation sequencing‐based multiplex gene assay performed on the metastatic tissue revealed an ETV6‐NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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26. Reduced dose of PTCy followed by adjuvant α-galactosylceramide enhances GVL effect without sacrificing GVHD suppression.
- Author
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Nakamura, Makoto, Meguri, Yusuke, Ikegawa, Shuntaro, Kondo, Takumi, Sumii, Yuichi, Fukumi, Takuya, Iwamoto, Miki, Sando, Yasuhisa, Sugiura, Hiroyuki, Asada, Noboru, Ennishi, Daisuke, Tomida, Shuta, Fukuda-Kawaguchi, Emi, Ishii, Yasuyuki, Maeda, Yoshinobu, and Matsuoka, Ken-ichi
- Subjects
GALACTOSYLCERAMIDASE ,GRAFT versus host disease ,HEMATOPOIETIC stem cell transplantation ,CYCLOPHOSPHAMIDE ,T cells - Abstract
Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by α-galactosylceramide (α-GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of α-GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4
+ Foxp3+ regulatory T cells. These studies indicate that α-GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk. [ABSTRACT FROM AUTHOR]- Published
- 2021
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27. Safety and antitumor activity of acalabrutinib for relapsed/refractory B‐cell malignancies: A Japanese phase I study.
- Author
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Izutsu, Koji, Ando, Kiyoshi, Ennishi, Daisuke, Shibayama, Hirohiko, Suzumiya, Junji, Yamamoto, Kazuhito, Ichikawa, Satoshi, Kato, Koji, Kumagai, Kyoya, Patel, Priti, Iizumi, Sakura, Hayashi, Nobuya, Kawasumi, Hisashi, Murayama, Kosho, and Nagai, Hirokazu
- Abstract
This multicenter, open‐label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B‐cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three‐part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty‐five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment‐related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression‐free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well‐tolerated in adult Japanese patients with B‐cell malignancies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan.
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Sunami, Kuniko, Naito, Yoichi, Aimono, Eriko, Amano, Toraji, Ennishi, Daisuke, Kage, Hidenori, Kanai, Masashi, Komine, Keigo, Koyama, Takafumi, Maeda, Takahiro, Morita, Sachi, Sakai, Daisuke, Kohsaka, Shinji, Tsuchihara, Katsuya, and Yoshino, Takayuki
- Subjects
CANCER hospitals ,GENETIC counseling ,INVESTIGATIONAL drugs ,NATIONAL health insurance - Abstract
Background: Since June 2019, cancer genomic profiling (CGP) tests have been reimbursed by the National Health Insurance system in Japan, with restrictions for government-designated hospitals with a molecular tumor board composed of multidisciplinary specialists, known as an expert panel (EP). The standardization of EPs is a critical challenge for implementing precision oncology in the clinical setting. Methods: Data on consecutive cases who underwent the CGP tests at 11 core hospitals between June 2019 and January 2020 were collected. We evaluated the proportions of cases that received genomically matched treatments, including investigational new drugs (INDs) based on CGP results, and/or for which genetic counseling was recommended. Two simulated cases were annotated by each EP. The annotated reports were then centrally assessed. Results: Each EP mainly discussed the applicability to genomically matched treatments and the necessity of performing genetic counseling. A pre-review of the report by key members in each EP reportedly made the EP conference more interactive and efficient, and thereby saved time. A total of 747 cases underwent CGP tests, 28 cases (3.7%) received genomically matched treatment, and 17 cases (2.3%) were referred for genetic counseling. Annotated reports for the simulated cases varied across the EPs, particularly the number of recommended IND trials, which seemed to be associated with the actual number of participants in IND trials. Conclusions: This investigation provides reference data for the application of precision oncology in a clinical setting. Further investigations on the standardization of clinical annotations are warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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29. Treatment outcomes of IgG4-producing marginal zone B-cell lymphoma: a retrospective case series.
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Sumii, Yuichi, Asada, Noboru, Sato, Yasuharu, Ohshima, Koh-ichi, Makita, Masanori, Yoshimoto, Yusuke, Sogabe, Yuka, Imajo, Kenji, Meguri, Yusuke, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Nobuharu, Matsuoka, Ken-ichi, Yoshino, Tadashi, and Maeda, Yoshinobu
- Subjects
IMMUNOGLOBULINS ,B cell lymphoma ,PROGNOSIS ,CANCER relapse ,TREATMENT effectiveness ,COMBINED modality therapy ,LONGITUDINAL method - Abstract
IgG4-producing marginal zone B-cell lymphomas (MZLs) have been recently proposed as a subtype of MZLs. Despite the abundant literature on pathophysiological features of this type of lymphoma, only a few retrospective studies pertaining to the treatment outcomes have been reported, and its prognosis remains unclear. We retrospectively analyzed seven patients with IgG4-producing MZLs diagnosed at our institute, with specific reference to treatment and outcomes. The median age was 69.0 years (55-79), and all were males. The median follow-up period was 66.6 months (8-121). All patients had localized disease; four patients had tumors of the ocular adnexa, whereas two had retroperitoneal tumors. Five patients were treated with irradiation (30 Gy/15 fr) (n = 4) or surgery (n = 1), resulting in tumor reduction. Two patients were treated by chemotherapy or irradiation. Among them, one commenced rituximab monotherapy, which led to an inadequate reduction of the tumor. Subsequent irradiation induced complete response (CR). The other patient experienced repeated relapses during follow-up and finally achieved CR by combination chemotherapy. Treatment was well tolerated in all cases, and none of the patients showed disease progression at the last follow-up visit. Our results indicate that the standard treatments for MZLs are generally appropriate for IgG4-producing MZL. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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30. Allogeneic hematopoietic stem cell transplantation in a prior lung transplant recipient.
- Author
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Fujiwara, Yuki, Matsuoka, Ken-ichi, Iwamoto, Miki, Sumii, Yuichi, Abe, Masaya, Mizuhara, Kentaro, Urata, Tomohiro, Saeki, Kyosuke, Meguri, Yusuke, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Sugita, Junichi, Kobayashi, Hajime, Oto, Takahiro, and Maeda, Yoshinobu
- Abstract
Hematological diseases after solid organ transplant (SOT) are an emerging issue as the number of long-term SOT survivors increases. Expertise in managing patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) after SOT from independent donors is needed; however, clinical reports of HSCT after SOT are limited, and the feasibility and risk are not well understood. In particular, HSCT in prior lung transplant recipients is thought to be complicated as the lung is immunologically distinct and is constantly exposed to the surrounding environment. Herein, we describe a case of successful HSCT in a patient with myelodysplastic syndromes who had previously received a lung transplant from a deceased donor for bronchiolitis obliterans syndrome. Reports about cases of HSCT after lung transplant are quite rare; thus, we discuss the mechanisms of immune tolerance through the clinical course of our case. This case suggests that HSCT after SOT can be considered a therapeutic option in cases where the transplanted organ is functionally retained and the hematological disease is in remission. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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31. Persistent hypogammaglobulinemia due to immunoglobulin class switch impairment by peri-transplant rituximab therapy.
- Author
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Mizuhara, Kentaro, Fujii, Nobuharu, Meguri, Yusuke, Takahashi, Takahide, Aoe, Michinori, Nakamura, Makoto, Seike, Keisuke, Sando, Yasuhisa, Fujii, Keiko, Abe, Masaya, Sumii, Yuichi, Urata, Tomohiro, Fujiwara, Yuki, Saeki, Kyosuke, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken-ichi, and Maeda, Yoshinobu
- Abstract
Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications of allogeneic hematopoietic stem cell transplantation (HSCT). Rituximab is effective for PTLD; however, rituximab can produce adverse effects, including hypogammaglobulinemia. Here, we present the case of an 18-year-old female with refractory cytopenia of childhood who developed persistent selective hypogammaglobulinemia with low immunoglobulin G (IgG) 2 and IgG4 levels and monoclonal protein after rituximab therapy against probable PTLD. Despite B-cell recovery, the serum IgG levels gradually declined, reaching < 300 mg/dL at 33 months after rituximab treatment. In addition, class-switched memory (CD27
+ IgD− ) B cells were limited in phenotypic analysis. These findings suggest that peri-HSCT rituximab may contribute to an abnormal B-cell repertoire induced by impaired immunoglobulin class switch. [ABSTRACT FROM AUTHOR]- Published
- 2020
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32. Single Cell Phenotypic Profiling of 27 DLBCL Cases Reveals Marked Intertumoral and Intratumoral Heterogeneity.
- Author
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Nissen, Michael D., Kusakabe, Manabu, Wang, Xuehai, Simkin, Guillermo, Gracias, Deanne, Tyshchenko, Kateryna, Hill, Ainsleigh, Meskas, Justin, Hung, Stacy, Chavez, Elizabeth A., Ennishi, Daisuke, Aoki, Tomohiro, Sarkozy, Clementine, Connors, Joseph M., Farinha, Pedro, Slack, Graham W., Gascoyne, Randy D., Brinkman, Ryan R., Scott, David W., and Steidl, Christian
- Abstract
Diffuse large B‐cell lymphoma (DLBCL) is the most common histologic subtype of non‐Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell‐of‐origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B‐cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B‐cells from each patient occupied unique regions in 37‐dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case, we were able to demonstrate direct correspondence between protein‐level phenotypic subsets and DNA mutation‐defined subclones. In summary, CyTOF analysis can resolve both intertumoral and intratumoral heterogeneity among primary samples and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones. © 2019 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]
- Published
- 2020
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33. Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation.
- Author
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Seike, Keisuke, Fujii, Nobuharu, Asano, Naomi, Ohkuma, Shigenori, Hirata, Yasushi, Fujii, Keiko, Sando, Yasuhisa, Nakamura, Makoto, Naito, Kazunori, Saeki, Kyosuke, Meguri, Yusuke, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Tsubaki, Kazuo, Otsuka, Fumio, Maeda, Yoshinobu, and Matsuoka, Ken-Ichi
- Subjects
HEMATOPOIETIC stem cell transplantation ,BLOOD platelet transfusion ,STEM cell transplantation ,HEMATOPOIETIC stem cells ,THROMBOCYTOPENIA treatment ,BLOOD grouping & crossmatching - Abstract
Background: Cross-matched platelet (cross-matched PLT) transfusion is effective for immune-mediated platelet transfusion refractoriness (PTR), but is more costly and time-consuming for physical cross-match than using standard PLT units. Recent studies have reported the utility of human leucocyte antigens (HLA) virtual cross-matched PLT (HLA-matched PLT) that is defined as HLA-A/B matched or no antibody against donor-specific antigen. Here, we evaluated the effect of HLA-matched PLTs for PTR in post hematopoietic stem cell transplant (HSCT) recipients.Study Design and Methods: Our study included a total of 241 PLTs in 16 patients who underwent HSCT at Okayama University Hospital between 2010 and 2017, receiving either HLA-matched or cross-matched PLTs. We calculated the 24-hour corrected count increments (CCI-24) to evaluate the effect of PLTs. A CCI-24 ≥ 4500 was considered to be a successful transfusion.Results: We analyzed 139 cross-matched PLTs and 102 HLA-matched PLTs. In the immune-mediated PTR, the rate of successful transfusion was 60.5% for cross-matched PLT and 63.4% for HLA-matched PLT (p = 0.825). On the other hand, the median CCI-24 for cross-matched PLT transfusions and HLA-matched PLT transfusions were 1856 and 5824 (p < 0.001), with a success rate of 28.1 and 54.1% in cases with non-immune-mediated PTR, respectively (p = 0.001).Conclusion: The effectiveness of HLA-matched PLT is not inferior to cross-matched PLT. This result indicates that physical cross-match can be omitted in post HSCT PTR. [ABSTRACT FROM AUTHOR]- Published
- 2020
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34. AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis.
- Author
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Dominguez, Pilar M., Melnick, Ari, Shaknovich, Rita, Teater, Matt, Ghione, Paola, Redmond, David, Elemento, Olivier, Zhengming Chen, Ennishi, Daisuke, Scott, David W., Cimmino, Luisa, Aifantis, Iannis, Chaudhuri, Jayanta, Gascoyne, Randy D., and Inghirami, Giorgio
- Subjects
CYTIDINE deaminase ,EPIGENETICS ,HETEROGENEITY ,GERMINAL centers ,DIFFUSE large B-cell lymphomas - Abstract
Epigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B-cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated with poor clinical outcome, yet the underlying mechanisms remain unclear. Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity maturation and facilitates DNA demethylation in germinal center (GC) B cells, is required for DLBCL pathogenesis and linked to inferior outcome. Here we show that AICDA overexpression causes more aggressive disease in BCL2-driven murine lymphomas. This phenotype is associated with increased cytosine methylation heterogeneity, but not with increased AICDA-mediated somatic mutation burden. Reciprocally, the cytosine methylation heterogeneity characteristic of normal GC B cells is lost upon AICDA depletion. These observations are relevant to human patients, since DLBCLs with high AICDA expression manifest increased methylation heterogeneity vs. AICDA-low DLBCLs. Our results identify AICDA as a driver of epigenetic heterogeneity in Bcell lymphomas with potential significance for other tumors with aberrant expression of cytidine deaminases. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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35. Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study.
- Author
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Kridel, Robert, Chan, Fong Chun, Mottok, Anja, Boyle, Merrill, Farinha, Pedro, Tan, King, Meissner, Barbara, Bashashati, Ali, McPherson, Andrew, Roth, Andrew, Shumansky, Karey, Yap, Damian, Ben-Neriah, Susana, Rosner, Jamie, Smith, Maia A., Nielsen, Cydney, Giné, Eva, Telenius, Adele, Ennishi, Daisuke, and Mungall, Andrew
- Subjects
B cell lymphoma ,SPONTANEOUS cancer regression ,IMMUNOTHERAPY ,CELL populations ,MORTALITY ,CELLS ,LYMPHOMAS ,GENETIC mutation ,DISEASE progression - Abstract
Background: Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the time course of FL clinical histories.Methods and Findings: Using a combination of whole genome sequencing, targeted deep sequencing, and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in 15 transformation cases and 6 progression cases, and measured the change in clonal population abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimens. This pattern was independent of time to transformation and treatment modality. By contrast, early progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immunochemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in an extension cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical end points. We found 12 genes that were more commonly mutated in transformed samples than in the preceding FL tumors, including TP53, B2M, CCND3, GNA13, S1PR2, and P2RY8. Moreover, ten genes were more commonly mutated in diagnostic specimens of patients with early progression, including TP53, BTG1, MKI67, and XBP1.Conclusions: Our results illuminate contrasting modes of evolution shaping the clinical histories of transformation and progression. They have implications for interpretation of evolutionary dynamics in the context of treatment-induced selective pressures, and indicate that transformation and progression will require different clinical management strategies. [ABSTRACT FROM AUTHOR]- Published
- 2016
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36. Concordance Between Recommendations From Multidisciplinary Molecular Tumor Boards and Central Consensus for Cancer Treatment in Japan.
- Author
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Naito, Yoichi, Sunami, Kuniko, Kage, Hidenori, Komine, Keigo, Amano, Toraji, Imai, Mitsuho, Koyama, Takafumi, Ennishi, Daisuke, Kanai, Masashi, Kenmotsu, Hirotsugu, Maeda, Takahiro, Morita, Sachi, Sakai, Daisuke, Watanabe, Kousuke, Shirota, Hidekazu, Kinoshita, Ichiro, Yoshioka, Masashiro, Mamesaya, Nobuaki, Ito, Mamoru, and Kohsaka, Shinji
- Published
- 2022
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37. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.
- Author
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Ortega-Molina, Ana, Boss, Isaac W, Canela, Andres, Pan, Heng, Jiang, Yanwen, Zhao, Chunying, Jiang, Man, Hu, Deqing, Agirre, Xabier, Niesvizky, Itamar, Lee, Ji-Eun, Chen, Hua-Tang, Ennishi, Daisuke, Scott, David W, Mottok, Anja, Hother, Christoffer, Liu, Shichong, Cao, Xing-Jun, Tam, Wayne, and Shaknovich, Rita
- Subjects
B cell lymphoma ,HISTONE methyltransferases ,TUMOR necrosis factors ,SOMATIC mutation ,GENE expression ,LYSINE ,DIFFUSE large B-cell lymphomas ,GENETIC repressors - Abstract
The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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38. Array comparative genomic hybridization reveals similarities between nodular lymphocyte predominant Hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma.
- Author
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Hartmann, Sylvia, Döring, Claudia, Vucic, Emily, Chan, Fong Chun, Ennishi, Daisuke, Tousseyn, Thomas, Wolf‐Peeters, Christiane, Perner, Sven, Wlodarska, Iwona, Steidl, Christian, Gascoyne, Randy D., and Hansmann, Martin‐Leo
- Subjects
HODGKIN'S disease ,LYMPHOCYTES ,B cell lymphoma ,T cells ,NF-kappa B ,FLUORESCENCE in situ hybridization ,IMMUNOHISTOCHEMISTRY ,CHROMOSOME abnormalities - Abstract
Nodular lymphocyte predominant Hodgkin lymphoma ( NLPHL) and T cell/histiocyte rich large B cell lymphoma ( THRLBCL) usually affect middle-aged men, show tumour cells with a B cell phenotype and a low tumour cell content. Whereas the clinical behaviour of NLPHL is indolent, THRLBCL presents with advanced stage disease and an aggressive behaviour. In the present study, array comparative genomic hybridization was performed in seven typical NLPHL, four THRLBCL-like NLPHL variants, six THRLBCL and four diffuse large B cell lymphomas ( DLBCL) derived from NLPHL. The number of genomic aberrations was higher in THRLBCL compared with typical and THRLBCL-like variant of NLPHL. Gains of 2p16.1 and losses of 2p11.2 and 9p11.2 were commonly observed in typical and THRLBCL-like variants of NLPHL as well as THRLBCL. Gains of 2p16.1, affecting the REL locus were confirmed in an independent cohort. Expression of the REL protein was observed at similar frequencies in typical and THRLBCL-like variant of NLPHL as well as THRLBCL (33-38%). In conclusion, the present study reveals further similarities between NLPHL and THRLBCL on the genomic level, confirming that these entities are part of a pathobiological spectrum with common molecular features, but varying clinical presentations. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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39. Comprehensive miRNA sequence analysis reveals survival differences in diffuse large B-cell lymphoma patients.
- Author
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Lim, Emilia L., Trinh, Diane L., Scott, David W., Chu, Andy, Krzywinski, Martin, Yongjun Zhao, Robertson, A. Gordon, Mungall, Andrew J., Schein, Jacqueline, Boyle, Merrill, Mottok, Anja, Ennishi, Daisuke, Johnson, Nathalie A., Steidl, Christian, Connors, Joseph M., Morin, Ryan D., Gascoyne, Randy D., and Marra, Marco A.
- Published
- 2015
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40. Duodenal follicular lymphoma: Comprehensive gene expression analysis with insights into pathogenesis.
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Takata, Katsuyoshi, Tanino, Motohiko, Ennishi, Daisuke, Tari, Akira, Sato, Yasuharu, Okada, Hiroyuki, Maeda, Yoshinobu, Goto, Naoe, Araki, Hiroshi, Harada, Mai, Ando, Midori, Iwamuro, Masaya, Tanimoto, Mitsune, Yamamoto, Kazuhide, Gascoyne, Randy D., and Yoshino, Tadashi
- Abstract
Follicular lymphoma ( FL) of the gastrointestinal tract, particularly duodenal follicular lymphoma ( DFL), is a rare variant of FL with indolent clinical behavior, and this disease is included in the 2008 World Health Organization classification system. In contrast to nodal follicular lymphoma ( NFL), DFL occurs most frequently in the second part of the duodenum, lacks follicular dendritic cell meshworks and has memory B-cell characteristics. However, its molecular pathogenesis is still unclear. In the present study, we examined 10 DFL, 18 NFL and 10 gastric MALT lymphoma samples using gene expression analysis. Quantitative RT- PCR experiments and immunohistochemical analysis for 72 formalin-fixed, paraffin-embedded tissues from an independent series, including 32 DFL, 19 gastric MALT lymphoma and 27 NFL samples, were performed for validation of microarray data. Gene expression profiles of the three lymphoma types were compared using 2918 differentially expressed genes ( DEG) and results suggested that DFL shares characteristics of MALT lymphoma. Among these DEG, CCL20 and MAd CAM-1 were upregulated in DFL and MALT but downregulated in NFL. In contrast, protocadherin gamma subfamily genes were upregulated in DFL and NFL. Quantitative RT- PCR and immunohistochemical studies demonstrated concordant results. Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT. We hypothesize that increased expression of CCL20 and MAd CAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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41. Germinal Center B-Cell-Like versus Non-Germinal Center B-Cell-Like as Important Prognostic Factor for Localized Nodal DLBCL.
- Author
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Habara, Toshiyuki, Sato, Yasuharu, Takata, Katsuyoshi, Iwaki, Noriko, Okumura, Hirokazu, Sonobe, Hiroshi, Tanaka, Takehiro, Orita, Yorihisa, Abd Al-Kader, Lamia, Ennishi, Daisuke, Asano, Naoko, and Yoshino, Tadashi
- Published
- 2012
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42. Association between insulin-like growth factor-1 polymorphisms and stomach cancer risk in a Japanese population.
- Author
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Ennishi, Daisuke, Shitara, Kohei, Ito, Hidemi, Hosono, Satoyo, Watanabe, Miki, Ito, Seiji, Sawaki, Akira, Yatabe, Yasushi, Yamao, Kenji, Tajima, Kazuo, Tanimoto, Mitsune, Tanaka, Hideo, Hamajima, Nobuyuki, and Matsuo, Keitaro
- Abstract
The insulin-like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non-cancer control subjects were enrolled in this case-control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per-allele model after adjusting for other risk factors (OR: 1.14 [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also observed a positive and dose-dependent association between the number of risk alleles and stomach cancer risk ( P-trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted. ( Cancer Sci 2011; 102: 2231-2235) [ABSTRACT FROM AUTHOR]
- Published
- 2011
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43. The utility of positron emission tomography/computed tomography in the staging of extranodal natural killer/T-cell lymphoma.
- Author
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Fujiwara, Hideaki, Maeda, Yoshinobu, Nawa, Yuichiro, Yamakura, Masayuki, Ennishi, Daisuke, Miyazaki, Yukihiro, Shinagawa, Katsuji, Hara, Masamichi, Matsue, Kosei, and Tanimoto, Mitsune
- Subjects
SINGLE-photon emission computed tomography ,T-cell lymphoma ,KILLER cells ,BONE marrow diseases ,BIOPSY ,PATIENTS ,DIAGNOSIS - Abstract
Natural killer (NK) ⁄ T-cell lymphoma cases are rarely discovered using positron emission tomography ⁄ computed tomography (PET ⁄ CT). We compared the utility of PET ⁄CT and that of conventional methods (CMs; CT with IV contrast, biopsies from primary sites, and bone marrow examinations) in the staging of extranodal NK⁄ T-cell lymphoma. Nineteen untreated patients with extranodal NK⁄ T cell lymphoma at three institutions were analyzed. PET ⁄CT and CMs were applied for initial workups following diagnosis. PET ⁄CT and CMs were compared and evaluated for their ability to detect tumor lesions and their influence on the stagingand treatment strategies. In total, 116 lesions were detected by CM and PET ⁄ CT. Using PET ⁄ CT, 108 lesions (93%) were discovered. The number of nodal lesions was 28: all were positive by PET ⁄CT and 26 (93%) by CMs. The number of extranodal lesions was 89: 84 (94%) and 54 (61%) lesions were positive by PET ⁄CT and CMs, respectively. PET ⁄CT was superior to CMs in detecting cutaneous lesions [31 ⁄ 31 lesions (100%) vs. 20 ⁄ 31 lesions (65%), respectively; P = 0.042]. Bone marrow involvement was confirmed pathologically in only seven patients; four cases (57%) were positive by PET ⁄ CT. Using CMs, ten patients (53%) were stages I–II and nine (47%) were stages III–IV. Using PET ⁄ CT, eight patients (42%) were in stages I–II and 11 (58%) were in stages III–IV. PET ⁄CT findings altered the stage and treatment strategy in two cases (11%). Our study demonstrated that PET ⁄CT is a useful tool for detecting extranodal lesions in NK⁄ T-cell lymphoma, particularly cutaneous lesions. PET ⁄CT may therefore influence future staging and treatment strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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44. Allogeneic hematopoietic stem cell transplantation for advanced extranodal natural killer/T-cell lymphoma, nasal type.
- Author
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Ennishi, Daisuke, Maeda, Yoshinobu, Fujii, Nobuharu, Kondo, Eisei, Shinagawa, Katsuji, Ikeda, Kazuma, Ichimura, Koichi, Yoshino, Tadashi, and Tanimoto, Mitsune
- Subjects
T-cell lymphoma ,KILLER cells ,LYMPHOMAS ,CORD blood transplantation ,STEM cell transplantation ,PATIENTS ,TUMORS ,PROGNOSIS - Abstract
The prognosis for patients with advanced or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is extremely poor. Thus, allogeneic stem cell transplantation (allo-HSCT) should be considered for this disease. However, reports of allo-HSCT for ENKL are limited because of the rarity of the disease. Here, we describe the clinical course of 12 cases of advanced and refractory ENKL treated with allo-HSCT, including five cases with cord blood transplant. With a median follow-up of 13 months (range, 1--168 months), seven patients are alive in remission, five have died, and one treatment-related death occurred. All patients with disease progression at transplant died of disease progression, whereas seven of eight patients with a complete or partial response are long-term survivors. Allo-HSCT is a feasible and promising consolidation therapy for advanced and relapsed ENKL. The disease status before allo-HSCT is well associated with general outcome, and thus induction treatment is very important for this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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45. Increased incidence of interstitial pneumonia by CHOP combined with rituximab.
- Author
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Ennishi, Daisuke, Terui, Yasuhito, Yokoyama, Masahiro, Mishima, Yuko, Takahashi, Shunji, Takeuchi, Kengo, Ikeda, Kazuma, Tanimoto, Mitsune, and Hatake, Kiyohiko
- Abstract
Several authors have reported interstitial pneumonia (IP) during rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, while others have encountered Pneumocystis jirovecii pneumonia during rituximab-combined bi-weekly CHOP. Herein, we report that 13 of 90 (14%) patients developed IP during R-CHOP therapy, compared with none of 105 patients treated with CHOP alone as a historical control. There were no differences in baseline data between patients undergoing the two therapies. Among R-CHOP-treated patients, serum beta-D-glucan was increased in 8 of 12 (75%) IP patients compared with none of 30 non-IP patients examined. In five IP patients who underwent sputum evaluation, two were positive for P. jirovecii by the polymerase chain reaction and another two were positive for Candida albicans. No other organisms were detected as causative pathogens. Treatment with steroids, sulfamethoxazole-trimethoprim (ST), and antifungals was effective. Our results suggest that R-CHOP raises the incidence of IP, possibly through increasing the susceptibility to P. jirovecii and fungal infection. The need for prophylactic antifungals and ST during R-CHOP should be evaluated by randomized controlled trials. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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46. Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV-infected CD20-positive B-cell lymphoma undergoing rituximab combination chemotherapy.
- Author
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Ennishi, Daisuke, Terui, Yasuhito, Yokoyama, Masahiro, Mishima, Yuko, Takahashi, Shunji, Takeuchi, Kengo, Okamoto, Hiroaki, Tanimoto, Mitsune, and Hatake, Kiyohiko
- Published
- 2008
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47. Correction to: The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan.
- Author
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Sunami, Kuniko, Naito, Yoichi, Aimono, Eriko, Amano, Toraji, Ennishi, Daisuke, Kage, Hidenori, Kanai, Masashi, Komine, Keigo, Koyama, Takafumi, Maeda, Takahiro, Morita, Sachi, Sakai, Daisuke, Kohsaka, Shinji, Tsuchihara, Katsuya, and Yoshino, Takayuki
- Subjects
CANCER hospitals - Abstract
A correction to this paper has been published: https://doi.org/10.1007/s10147-021-01897-w [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
48. Author Correction: 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy.
- Author
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Sando, Yasuhisa, Matsuoka, Ken-ichi, Sumii, Yuichi, Kondo, Takumi, Ikegawa, Shuntaro, Sugiura, Hiroyuki, Nakamura, Makoto, Iwamoto, Miki, Meguri, Yusuke, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Utsunomiya, Atae, Oka, Takashi, and Maeda, Yoshinobu
- Subjects
AMINOLEVULINIC acid ,PHOTODYNAMIC therapy ,T-cell lymphoma - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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49. 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy.
- Author
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Sando, Yasuhisa, Matsuoka, Ken-ichi, Sumii, Yuichi, Kondo, Takumi, Ikegawa, Shuntaro, Sugiura, Hiroyuki, Nakamura, Makoto, Iwamoto, Miki, Meguri, Yusuke, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Utsunomiya, Atae, Oka, Takashi, and Maeda, Yoshinobu
- Subjects
PHOTODYNAMIC therapy ,LEUKEMIA ,CELL death ,BIOMARKERS ,HEMATOLOGY - Abstract
Photodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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50. Rituximab plus CHOP as an initial chemotherapy for patients with disseminated MALT lymphoma.
- Author
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Ennishi, Daisuke, Yokoyama, Masahiro, Mishima, Yuko, Watanabe, Chie, Terui, Yasuhito, Takahashi, Shunji, Takeuchi, Kengo, Ikeda, Kazuma, Tanimoto, Mitsune, and Hatake, Kiyohiko
- Subjects
LETTERS to the editor ,DRUG therapy - Abstract
A letter to the editor is presented about the use of rituximab in combination with cyclosphosphamide, doxorubicin, vincristine, prednisone (CHOP) as chemotherapy for patients with disseminated mucosa-associated lymphoid tissue (MALT) lymphoma.
- Published
- 2007
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