Publications by authors named "Naoyuki Katayama"

217 Publications

Multi-centre study of cement-in-cement and in-cement femoral revision total hip arthroplasty using polished, stainless steel stems.

J Orthop Sci 2021 Aug 11. Epub 2021 Aug 11.

Gifu Municipal Hospital, Joint Reconstruction Center, Japan. Electronic address:

Background: Exposure of the acetabular component during revision total hip arthroplasty is often difficult and stems are often difficult to remove. Polished and tapered cemented stems are easily removed and can be easily reconstructed by either cement-in-cement or in-cement technique. This study was a retrospective review of the medium-term outcomes of revision total hip arthroplasty conducted with the Exeter stem fixed by cement-in-cement or in-cement method in four institutions.

Methods: This study included hips (n = 103) reconstructed by cement-in-cement or in-cement technique on the femoral side during revision total hip arthroplasty in four institutions between 2003 and 2015. The mean age at surgery was 71.1 years (range, 43-86 years), and the mean follow-up period was 5.6 years (range, 0-13 years).

Results: Revision arthroplasty was required for acetabular component complications in 69 hips, for dislocation in 25, for infection in eight, and for stem fracture in one hip. Re-revision was required in 10 hips for: infection (n = 6), acetabular component complications (n = 3), and dislocation (n = 1). No radiographic loosening, cement fractures, or osteolysis of the femoral components were observed. Ten-year survival rate was 99% with the endpoint of femoral revision surgery, and 100% with the endpoint of femoral aseptic loosening.

Conclusions: The medium-term outcomes of revision total hip arthroplasty on the femoral side conducted using the cement-in-cement or in-cement technique were favourable, with no cases of aseptic loosening. As long as the bone-cement interface remains robust, there is no need to remove all the cement, and the cement-in-cement or in-cement technique should be used for reconstruction.
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http://dx.doi.org/10.1016/j.jos.2021.06.017DOI Listing
August 2021

Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria.

Support Care Cancer 2021 Aug 10. Epub 2021 Aug 10.

Department of Hematology and Oncology, Mie University Hospital, Mie, Japan.

Purpose: This study aimed to clarify the clinical utility of oral management to prevent bloodstream infections by oral bacteria microbiologically in patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT).

Methods: Ten consecutive patients with hematological malignancies undergoing ASCT were enrolled in this study. We implemented dental treatments before transplantation, if required, and carried out oral hygiene instructions and oral management every other day after transplantation. Molecular analysis of bacterial DNA for seven oral species using a polymerase chain reaction (PCR) assay was performed for oral samples and peripheral blood once a week for 3 weeks after transplantation.

Results: Periodontitis was found in all 10 patients (mild grade in 3 and middle grade in 7) for whom basic periodontal therapy was conducted. Necessary dental procedures, including tooth extraction were performed in 5 patients. After transplantation, oral mucositis occurred in 10 patients (grade 1 in 3, grade 2 in 2, and grade 3 in 5) for whom oral hygiene instruction and oral care were continued every other day. PCR-identified three to six bacterial species in oral samples from nine patients, but none in peripheral blood from any patient during the observation period.

Conclusions: Our study suggests that oral management could prevent bloodstream infections by oral bacteria in ASCT recipients despite the existence of periodontitis or oral mucositis. Its utility was confirmed by microbiological evidence based on molecular data.
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http://dx.doi.org/10.1007/s00520-021-06462-9DOI Listing
August 2021

MPL exon 10 mutations other than canonical MPL W515L/K mutations identified by in-house MPL exon 10 direct sequencing in essential thrombocythemia.

Int J Hematol 2021 May 26;113(5):618-621. Epub 2021 Mar 26.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.

MPL exon 10 mutations are one of the driver mutations in essential thrombocythemia (ET) or myelofibrosis (MF). We have established an in-house MPL mutation analysis system, covering the entire region of MPL exon 10 by direct sequencing. Since 2009, MPL exon 10 mutation analysis has been performed for diagnosis of myeloproliferative neoplasms (MPN) without JAK2 V617F or CALR exon 9 mutations. So far, 11 cases of MPL exon 10 mutation have been found in 51 patients with suspected MPN. In patients with ET, we detected five non-canonical MPL mutations including one novel mutation, MPL R514_P518delinsK, and one canonical MPL W515L mutation. Notably, three ET patients without canonical MPL mutations had thrombotic events. Meanwhile, in primary or secondary MF, only canonical MPL W515L/K mutations were found. Further cases need to be examined to elucidate the full MPL mutation profile in MPN. However, our data indicate that analysis of the whole of MPL exon 10 is warranted for the diagnosis of MPL mutations, especially in ET, and that the use of Japanese commercial laboratory tests that only detect canonical MPL W515L/K mutations may miss a significant percentage of MPL exon 10 mutations, which could delay the administration of anti-thrombotic therapy.
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http://dx.doi.org/10.1007/s12185-021-03134-6DOI Listing
May 2021

Tet1 is not required for myeloid leukemogenesis by MLL-ENL in novel mouse models.

PLoS One 2021 11;16(3):e0248425. Epub 2021 Mar 11.

Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

The Ten Eleven Translocation 1 (TET1) gene encodes an epigenetic modifying molecule that is involved in demethylation of 5-methylcytosine. In hematological malignancies, loss-of-function mutations of TET2, which is one of the TET family genes including TET1, are frequently found, while the mutations of TET1 are not. However, clinical studies have revealed that TET1 is highly expressed in some cases of the hematological malignancies including acute myeloid leukemia. Indeed, studies by mouse models using conventional Tet1 knockout mice demonstrated that Tet1 is involved in myeloid leukemogenesis by Mixed Lineage Leukemia (MLL) fusion gene or TET2 mutant. Meanwhile, the other study showed that Tet1 is highly expressed in hematopoietic stem cells (HSCs), and that deletion of Tet1 in HSCs enhances potential self-renewal capacity, which is potentially associated with myeloid leukemogenesis. To examine the role of Tet1 in myeloid leukemogenesis more precisely, we generated novel conditional Tet1-knockout mice, which were used to generate the compound mutant mice by crossing with the inducible MLL-ENL transgenic mice that we developed previously. The leukemic immortalization in vitro was not critically affected by conditional ablation of Tet1 in HSCs with the induced expression of MLL-ENL or in hematopoietic progenitor cells retrovirally transduced with MLL-ENL. In addition, the leukemic phenotypes caused by the induced expression of MLL-ENL in vivo was not also critically affected in the compound mutant mouse model by conditional ablation of Tet1, although we found that the expression of Evi1, which is one of critical target genes of MLL fusion gene, in tumor cells was remarkably low under Tet1-ablated condition. These results revealed that Tet1 was dispensable for the myeloid leukemogenesis by MLL-ENL, suggesting that the therapeutic application of Tet1 inhibition may need careful assessment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248425PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951824PMC
March 2021

Early central nervous system relapse of monomorphic epitheliotropic intestinal T-cell lymphoma after cord blood transplantation.

Int J Hematol 2021 Jul 1;114(1):129-135. Epub 2021 Mar 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.
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http://dx.doi.org/10.1007/s12185-021-03107-9DOI Listing
July 2021

Artificial intelligence diagnostic system predicts multiple Lugol-voiding lesions in the esophagus and patients at high risk for esophageal squamous cell carcinoma.

Endoscopy 2021 Feb 4. Epub 2021 Feb 4.

Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: It is known that an esophagus with multiple Lugol-voiding lesions (LVLs) after iodine staining is high risk for esophageal cancer; however, it is preferable to identify high-risk cases without staining because iodine causes discomfort and prolongs examination times. This study assessed the capability of an artificial intelligence (AI) system to predict multiple LVLs from images that had not been stained with iodine as well as patients at high risk for esophageal cancer.

Methods: We constructed the AI system by preparing a training set of 6634 images from white-light and narrow-band imaging in 595 patients before they underwent endoscopic examination with iodine staining. Diagnostic performance was evaluated on an independent validation dataset (667 images from 72 patients) and compared with that of 10 experienced endoscopists.

Results: The sensitivity, specificity, and accuracy of the AI system to predict multiple LVLs were 84.4 %, 70.0 %, and 76.4 %, respectively, compared with 46.9 %, 77.5 %, and 63.9 %, respectively, for the endoscopists. The AI system had significantly higher sensitivity than 9/10 experienced endoscopists. We also identified six endoscopic findings that were significantly more frequent in patients with multiple LVLs; however, the AI system had greater sensitivity than these findings for the prediction of multiple LVLs. Moreover, patients with AI-predicted multiple LVLs had significantly more cancers in the esophagus and head and neck than patients without predicted multiple LVLs.

Conclusion: The AI system could predict multiple LVLs with high sensitivity from images without iodine staining. The system could enable endoscopists to apply iodine staining more judiciously.
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http://dx.doi.org/10.1055/a-1334-4053DOI Listing
February 2021

[Therapy-related acute promyelocytic leukemia with complex karyotype accompanied by cryptic PML/RARA on chromosome 15 by metaphase FISH].

Rinsho Ketsueki 2020 ;61(11):1577-1583

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 53-year-old male presented with pancytopenia for 13 months. He had a past history of follicular lymphoma and hypopharyngeal cancer, which was treated via chemotherapy and radiotherapy. Bone marrow aspiration biopsy of the patient revealed a hypocellular marrow with 32% of hypergranular blasts without Auer bodies. There were also erythroid and megakaryocytic dysplasia in the bone marrow. Although the PML/RARA transcript was detected by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR), the G-banding karyotype analysis showed a complex karyotype without t (15;17). The PML/RARA fusion signal was identified on chromosome 15 by metaphase FISH. The patient was diagnosed of therapy-related acute promyelocytic leukemia (t-APL) with cryptic PML/RARA. He successfully attained molecular complete remission with all-trans retinoic acid (ATRA) and two courses of arsenic trioxide (ATO). He was subsequently administered nivolumab without ATRA maintenance therapy because of a progressing metastasis of a hypopharyngeal cancer to the lung. The patient had a relapse of t-APL following nine courses of nivolumab, 8 months after ending consolidation therapy with ATO. Reinduction therapy with ATRA was not effective for the relapsed t-APL that was accompanied by del (5q) and monosomy 7. Little has been previously reported on t-APL with cryptic PML/RARA. Therefore, the clinical course of this patient may provide useful insights about the characteristics of t-APL with cryptic PML/RARA.
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http://dx.doi.org/10.11406/rinketsu.61.1577DOI Listing
February 2021

CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression.

Oncol Lett 2021 Jan 12;21(1):36. Epub 2020 Nov 12.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie 514-8507, Japan.

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC. Furthermore, suppressive subsets in the local tumor microenvironment, such as tumor-associated macrophages (TAMs), which promote tumor progression, cannot be ignored to overcome immunotherapy resistance. The aims of the present study were to classify primary BC cases based on the TIL levels and PD-L1 status, and to identify suppressive immune subsets in each categorized group. A retrospective analysis of 73 patients with invasive BC was performed. The frequency of TILs was evaluated in HE-stained slides (10% cutoff), and PD-L1 levels (SP142; 1% cutoff), as well as immune subsets (CD3, CD8, FOXP3, CD20, CD68 and CD204 cells) were assessed using immunohistochemistry. It was revealed that 22% (16/73) of the tumors were categorized as TILPD-L1, of which 69% (11/16) were TN type. By contrast, 66% (48/73) of the tumors were categorized as TILPD-L1, of which 77% (37/48) were HR and HER2 types. The number of CD204 M2-type macrophages was significantly associated with high histological grade (P=0.0246) and high Ki-67 (P=0.0152), whereas CD68 macrophages were not associated with these factors. Furthermore, CD204 macrophages and FOXP3 Tregs accumulated in 88% (14/16) and 63% (10/16) of TILPD-L1 tumors, respectively, compared with 20.8% (10/48) and 27.1% (13/48) of TILPD-L1 tumors. In conclusion, 22% of BC tumors were classified as TILPD-L1 (69% were TN), which were enriched with suppressive immune subsets. These cell types may serve as potential novel immunotherapeutic targets.
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http://dx.doi.org/10.3892/ol.2020.12297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693484PMC
January 2021

DA-EPOCH-R combined with high-dose methotrexate in patients with newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma: a single-arm, open-label, phase II study.

Haematologica 2020 09 1;105(9):2308-2315. Epub 2020 Sep 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis and a high frequency of central nervous system relapse after standard immunochemotherapy. We conducted a phase II study to investigate the efficacy and safety of dose-adjusted (DA)- EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) combined with high-dose methotrexate (HD-MTX) in newly diagnosed patients with CD5+ DLBCL. Previously untreated patients with stage II to IV CD5+ DLBCL according to the 2008 World Health Organization classification were eligible. Four cycles of DA-EPOCH-R followed by two cycles of HD-MTX and four additional cycles of DAEPOCH- R (DA-EPOCH-R/HD-MTX) were planned as the protocol treatment. The primary end point was 2-year progression-free survival (PFS). Between September 25, 2012, and November 11, 2015, we enrolled 47 evaluable patients. Forty-five (96%) patients completed the protocol treatment. There were no deviations or violations in the DA-EPOCH-R dose levels. The complete response rate was 91%, and the overall response rate was 94%. At a median follow up of 3.1 years (range, 2.0-4.9 years), the 2- year PFS was 79% [95% confidence interval (CI): 64-88]. The 2-year overall survival was 89% (95%CI: 76-95). Toxicity included grade 4 neutropenia in 46 (98%) patients, grade 4 thrombocytopenia 12 (26%) patients, and febrile neutropenia in 31 (66%) patients. No treatment-related death was noted during the study. DA-EPOCH-R/HD-MTX might be a first-line therapy option for stage II-IV CD5+ DLBCL and warrants further investigation. (Trial registered at: UMIN-CTR: UMIN000008507.).
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http://dx.doi.org/10.3324/haematol.2019.231076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556618PMC
September 2020

Risk factors for cisplatin-induced acute kidney injury: A pilot study on the usefulness of genetic variants for predicting nephrotoxicity in clinical practice.

Mol Clin Oncol 2020 Nov 1;13(5):58. Epub 2020 Sep 1.

Department of Medical Oncology, Mie University Graduate School of Medicine, Tsu, Mie 5148507, Japan.

Several studies have reported risk factors for predicting cisplatin-induced acute kidney injury (AKI), including old age, female sex, smoking, hypoalbuminemia, hypokalemia, hypomagnesemia, a high body surface area, advanced cancer and the total dose of cisplatin administered. Recently, some studies have focused on the associations between genetic alterations in the genes coding for renal drug transporters, such as organic cation transporter 2 (OCT2), and the nephrotoxicity of cisplatin. However, genetic variants have not been fully elucidated for clinical use. Patients who had received cisplatin (≥50 mg/m)-containing chemotherapy as a first-line treatment were considered as eligible for the present study. The occurrence of AKI and its associations with baseline characteristics, conventional biomarkers and single-nucleotide variants (SNV) were assessed. AKI was defined as an increase in the serum creatinine level of >0.3 mg/dl or to 1.5-2 times the baseline level. Genotyping was conducted using the DMET platform (DMET Plus), which characterizes 1,936 genetic variants (1,931 SNV and 5 copy number variations) in 231 genes. Between April 2014 and June 2016, a total of 28 patients (22 men and 6 women) were enrolled. AKI occurred in 8 of the 28 enrolled patients (28.6%). Univariate analyses demonstrated that the urinary β2-microglobulin level and body surface area were significantly higher in the AKI group (P<0.05). As regards the associations between AKI and SNV, none of the examined SNV were found to be associated with cisplatin-induced AKI. The findings of the present study suggested that certain clinical factors were associated with the onset of AKI, but no associations were identified with genetic factors, including OCT2. Although this was a small pilot study, the findings indicated that genetic factors may not be of value for predicting AKI in clinical practice.
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http://dx.doi.org/10.3892/mco.2020.2127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484732PMC
November 2020

Regular-triangle trimer and charge order preserving the Anderson condition in the pyrochlore structure of CsWO.

Nat Commun 2020 Jun 19;11(1):3144. Epub 2020 Jun 19.

Department of Applied Physics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.

Since the discovery of the Verwey transition in magnetite, transition metal compounds with pyrochlore structures have been intensively studied as a platform for realizing remarkable electronic phase transitions. We report on a phase transition that preserves the cubic symmetry of the β-pyrochlore oxide CsWO, where each of W 5d electrons are confined in regular-triangle W trimers. This trimer formation represents the self-organization of 5d electrons, which can be resolved into a charge order satisfying the Anderson condition in a nontrivial way, orbital order caused by the distortion of WO octahedra, and the formation of a spin-singlet pair in a regular-triangle trimer. An electronic instability due to the unusual three-dimensional nesting of Fermi surfaces and the strong correlations of the 5d electrons characteristic of the pyrochlore oxides are both likely to play important roles in this charge-orbital-spin coupled phenomenon.
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http://dx.doi.org/10.1038/s41467-020-16873-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305186PMC
June 2020

A non-selective endothelin receptor antagonist bosentan modulates kinetics of bone marrow-derived cells in ameliorating pulmonary hypertension in mice.

Pulm Circ 2020 Apr-Jun;10(2):2045894020919355. Epub 2020 May 14.

Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.

The aim of this study was to investigate whether a dual endothelin receptor antagonist bosentan modulates the kinetics of bone marrow-derived stem cells in inhibiting the development of pulmonary hypertension. Bone marrow chimeric mice, transplanted with enhanced green fluorescent protein (eGFP)-positive bone marrow mononuclear cells, were exposed to hypobaric hypoxia or kept in the ambient air, and were daily treated with bosentan sodium salt or saline for 21 days. After the treatment period, right ventricular pressure was measured and pulmonary vascular morphometry was conducted. Incorporation of bone marrow-derived cells was analyzed by immunohistochemistry. Gene expression and protein level in the lung tissue were evaluated by quantitative real-time PCR and western blotting, respectively. The results showed that, in hypoxic mice, right ventricular pressure and the percentage of muscularized vessel were increased and pulmonary vascular density was decreased, each of which was reversed by bosentan. Bone marrow-derived endothelial cells and macrophages in lungs were increased by hypoxia. Bosentan promoted bone marrow-derived endothelial cell incorporation but inhibited macrophage infiltration into lungs. Quantitative real-time PCR analysis revealed that interleukin 6, stromal cell-derived factor-1, and monocyte chemoattractant protein-1 were upregulated by hypoxia, in which interleukin 6 and monocyte chemoattractant protein-1 were downregulated and stromal cell-derived factor-1 was upregulated by bosentan. Protein level of endothelial nitric oxide synthase (eNOS) in the whole lung was significantly upregulated by hypoxia, which was further upregulated by bosentan. Bosentan modulated kinetics of bone marrow-derived ECs and macrophages and related gene expression in lungs in ameliorating pulmonary hypertension in mice. Altered kinetics of bone marrow-derived stem cells may be a novel mechanism of the endothelin receptor blockade in vivo and confer a new understanding of the therapeutic basis for pulmonary hypertension.
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http://dx.doi.org/10.1177/2045894020919355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238854PMC
May 2020

A novel CDK-independent function of p27 in preciliary vesicle trafficking during ciliogenesis.

Biochem Biophys Res Commun 2020 06 16;527(3):716-722. Epub 2020 May 16.

Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan. Electronic address:

p27, a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors, is now known as a multifunctional protein that plays crucial roles in cell architecture and migration by regulating rearrangements of the actin cytoskeleton and microtubules. The intracellular level of p27 is increased by anti-proliferative stimuli, such as mitogen deprivation and contact inhibition, which also induce formation of primary cilia, microtubule-based membranous organelles that protrude from the cell surface. However, it remains unknown whether p27 is associated with ciliogenesis. Here, we have generated p27-knockout hTERT-immortalized human retinal pigment epithelial cells, and found that ciliogenesis is almost completely disrupted in p27-knockout cells. The defect of ciliogenesis is rescued by the exogenous expression of wild-type p27 and, surprisingly, its 86-140 amino acid region, which is neither responsible for CDK inhibition nor remodeling of the actin cytoskeleton and microtubules. Moreover, transmission electron microscopy and immunofluorescence analyses reveal that p27 abrogation impairs one of the earliest events of ciliogenesis, docking of the Ehd1-associated preciliary vesicles to the distal appendages of the basal body. Our findings identify a novel CDK-independent function of p27 in primary cilia formation.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.048DOI Listing
June 2020

Detecting early gastric cancer: Comparison between the diagnostic ability of convolutional neural networks and endoscopists.

Dig Endosc 2021 Jan 2;33(1):141-150. Epub 2020 Jun 2.

AI Medical Service Inc, Tokyo, Japan.

Objectives: Detecting early gastric cancer is difficult, and it may even be overlooked by experienced endoscopists. Recently, artificial intelligence based on deep learning through convolutional neural networks (CNNs) has enabled significant advancements in the field of gastroenterology. However, it remains unclear whether a CNN can outperform endoscopists. In this study, we evaluated whether the performance of a CNN in detecting early gastric cancer is better than that of endoscopists.

Methods: The CNN was constructed using 13,584 endoscopic images from 2639 lesions of gastric cancer. Subsequently, its diagnostic ability was compared to that of 67 endoscopists using an independent test dataset (2940 images from 140 cases).

Results: The average diagnostic time for analyzing 2940 test endoscopic images by the CNN and endoscopists were 45.5 ± 1.8 s and 173.0 ± 66.0 min, respectively. The sensitivity, specificity, and positive and negative predictive values for the CNN were 58.4%, 87.3%, 26.0%, and 96.5%, respectively. These values for the 67 endoscopists were 31.9%, 97.2%, 46.2%, and 94.9%, respectively. The CNN had a significantly higher sensitivity than the endoscopists (by 26.5%; 95% confidence interval, 14.9-32.5%).

Conclusion: The CNN detected more early gastric cancer cases in a shorter time than the endoscopists. The CNN needs further training to achieve higher diagnostic accuracy. However, a diagnostic support tool for gastric cancer using a CNN will be realized in the near future.
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http://dx.doi.org/10.1111/den.13688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818187PMC
January 2021

Guest editorial: B1 cells: their ontogeny and malignant counterpart.

Authors:
Naoyuki Katayama

Int J Hematol 2020 05 8;111(5):619-621. Epub 2020 Apr 8.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

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http://dx.doi.org/10.1007/s12185-020-02868-zDOI Listing
May 2020

[Successful treatment with a combination of elotuzumab, lenalidomide and dexamethasone of extramedullary disease in a patient with refractory multiple myeloma].

Rinsho Ketsueki 2020 ;61(3):223-227

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 56-year-old man diagnosed with multiple myeloma was treated with CBD (cyclophosphamide, bortezomib, and dexamethasone; DEX), which was discontinued because of bortezomib-associated adverse events. Thereafter, he was treated with Ld (lenalidomide; LEN+DEX) followed by high-dose chemotherapy with autologous stem cell rescue, resulting in a complete response. Ld as maintenance therapy was discontinued because of immune thrombocytopenia, resulting in disease progression. Although treatment was switched to Pd (pomalidomide+DEX), DLd (daratumumab+LEN+DEX), and IRd (ixazomib+LEN+DEX); the patient's M protein level continued to increase and the extramedullary disease expanded despite radiotherapy. He was treated with E-Ld (elotuzumab+LEN+DEX) after 3 cycles of short VAD (vincristine, doxorubicin, and DEX). The extramedullary disease disappeared after 8 cycles of E-Ld. To the best of our knowledge, this is the first report showing the effectiveness of E-Ld treatment for extramedullary disease of a heavily treated patient for multiple myeloma. We believe that the clinical course of this patient provides useful insights about the antimyeloma mechanism of elotuzumab.
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http://dx.doi.org/10.11406/rinketsu.61.223DOI Listing
May 2020

Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy.

Int J Hematol 2020 May 28;111(5):686-691. Epub 2020 Jan 28.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients receiving current standard chemotherapy. The association between VIPN and genetic polymorphisms is largely unknown in adult lymphoma patients. To examine the possible relationship between known genetic polymorphisms in patients with pediatric acute lymphoblastic leukemia and incidence of VIPN in adult patients with B cell lymphoma, we examined CEP72 rs924607, ETAA1 rs17032980, MTNR1B rs12786200, CYP3A5 rs776746, rs7963521, and rs1045644 genetic polymorphisms in samples from 56 adult patients with B-cell lymphoma who received rituximab, cyclophosphamide, doxorubicin, VCR, and prednisone (R-CHOP) chemotherapy. Mutation analysis was performed by direct sequencing. The median age was 65 years (range 30-79). The median cumulative dose of VCR was 12 mg (range 2-16). VIPN was documented in 42 patients (75%), and 9 (16%) had grade 2-4 VIPN. Age, impaired glucose tolerance, number of cycles of R-CHOP, and VCR cumulative dose were not associated with incidence of VIPN. There was no association between the incidence of grade 2-4 or any grade VIPN and these six genetic polymorphisms. These results indicate that CEP72, MTNR1B, ETAA1, CYP3A5, rs7963521, and rs1045644 genetic polymorphisms are not associated with VIPN in patients with B-cell lymphoma who received R-CHOP.
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http://dx.doi.org/10.1007/s12185-020-02832-xDOI Listing
May 2020

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

Cancer Immunol Immunother 2020 Apr 24;69(4):663-675. Epub 2020 Jan 24.

Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, 1577 Kurimamachiya-cho, Tsu, Mie, 514-8507, Japan.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8 T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.
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http://dx.doi.org/10.1007/s00262-020-02483-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113205PMC
April 2020

Achievement of long-term remission of disseminated histoplasmosis in an AIDS patient.

Med Mycol Case Rep 2020 Mar 19;27:25-28. Epub 2019 Dec 19.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.

Histoplasmosis, a fungal infection caused by , is poor prognosis once it disseminated, especially in immunocompromised patients. A 50-year-old Japanese-Brazilian male with multiple cervical lymphadenopathies was diagnosed as disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS). Anti-fungal therapy was initiated followed by anti-retroviral therapy (ART). He achieved long-term remission by treatment with voriconazole. Here we report a case of an AIDS patient with disseminated histoplasmosis who achieved long-term survival in non-endemic area.
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http://dx.doi.org/10.1016/j.mmcr.2019.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938860PMC
March 2020

Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein.

Sci Rep 2019 12 30;9(1):20359. Epub 2019 Dec 30.

Department of Pharmacy, Osaka University Hospital, Suita, Osaka, 565-0871, Japan.

Methotrexate (MTX) is an antifolate agent used for the treatment of various malignancies and is eliminated by breast cancer resistance protein (BCRP). Because febuxostat (FBX) is known to inhibit BCRP activity, FBX might exacerbate MTX-related adverse effects. In this study, we examined the drug-drug interaction between FBX and MTX in BCRP-expressing membrane vesicles. Moreover, we retrospectively investigated the impact of FBX on MTX-related adverse effects in 38 patients (144 cycles) receiving high-dose MTX therapy (HDMTX). The Food and Drug Administration Adverse Event Reporting System (FAERS) database and human hepatocellular carcinoma cell line HepG2 cells were used to evaluate the effects of FBX on MTX-induced hepatotoxicity. In the membrane vesicle study, FBX significantly inhibited BCRP-mediated transport of MTX. Concomitant FBX significantly increased the incidence of hepatotoxicity, but not of nephrotoxicity and hematological toxicity in patients receiving HDMTX. FAERS database analyses revealed that the reporting odds ratio of FBX for MTX-induced hepatotoxicity was 4.16 (95% CI: 2.89-5.98). Co-incubated FBX significantly decreased the cell viability and increased cytotoxicity in MTX-treated HepG2 cells. These findings suggest that concomitant FBX enhances MTX-induced hepatotoxicity by inhibiting hepatic BCRP. These findings provide important information for the safe management of HDMTX therapy in clinical settings.
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http://dx.doi.org/10.1038/s41598-019-56900-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937279PMC
December 2019

Ontogeny of human B1 cells.

Int J Hematol 2020 May 12;111(5):628-633. Epub 2019 Nov 12.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Mie, Japan.

B1 cells, which are distinct from conventional B cells, are a rare B lymphocyte subpopulation that plays a pivotal role in innate immunity. Extensive previous studies have revealed the functions and ontogeny of murine B1 cells, but the properties of human B1 cells have just begun to be uncovered over the past decade. The phenotype of human B1 cells has recently been proposed, facilitating further studies. Here, we review the latest knowledge on human B1 cells, especially their ontogeny. A previous study using xenotransplantation models showed that human hematopoietic stem cells (HSCs) derived from cord blood or adult bone marrow can produce B1 cells in vivo. A recent study by our group reported that human B1 cells in peripheral blood are derived from adult HSCs and persist for approximately 3 years in situ. These findings suggest that adult human HSCs have the ability to produce B1 cells and contribute to maintenance of the adult B1 cell pool in peripheral blood. Further understanding of human B1 cell functions and ontogeny may elucidate the pathogenesis of B cell malignancies and autoimmune diseases.
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http://dx.doi.org/10.1007/s12185-019-02775-yDOI Listing
May 2020

Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells.

J Exp Med 2020 02;217(2)

Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan.

This report addresses whether small molecules can deplete FoxP3-expressing regulatory T (T reg) cells, thereby augmenting antitumor immunity. Imatinib, a tyrosine kinase inhibitor of oncogenic BCR-ABL protein expressed by chronic myelogenous leukemia (CML) cells, possesses off-targets including LCK expressed in T cells. We showed that imatinib-treated CML patients in complete molecular remission (CMR) exhibited selective depletion of effector T reg (eT reg) cells and significant increase in effector/memory CD8+ T cells while non-CMR patients did not. Imatinib at CML-therapeutic concentrations indeed induced apoptosis specifically in eT reg cells and expanded tumor antigen-specific CD8+ T cells in vitro in healthy individuals and melanoma patients, and suppressed colon tumor growth in vivo in mice. Mechanistically, because of FoxP3-dependent much lower expression of LCK and ZAP-70 in T reg cells compared with other T cells, imatinib inhibition of LCK further reduced their TCR signal intensity, rendering them selectively susceptible to signal-deprived apoptotis. Taken together, eT reg cell depletion by imatinib is instrumental in evoking effective immune responses to various cancers.
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http://dx.doi.org/10.1084/jem.20191009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041710PMC
February 2020

Life-Threatening Tongue and Retropharyngeal Hemorrhage in a Patient with Hemophilia A with Inhibitors.

Am J Case Rep 2019 Jul 15;20:1022-1026. Epub 2019 Jul 15.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

BACKGROUND Massive tongue hemorrhage in patients with hemophilia is a medical emergency because it can lead to airway obstruction. However, managing bleeding in patients with inhibitors is more difficult than in patients without inhibitors. We report a case of life-threatening massive tongue and retropharyngeal hematoma in a patient with hemophilia A who had inhibitors. CASE REPORT The patient was a 71-year-old man with severe hemophilia A with high-responding inhibitors. He was admitted to our hospital with dysarthria and dysphagia secondary to a massive tongue hematoma. Although bypassing therapy was started immediately after admission, he rapidly developed an airway obstruction and cardiopulmonary arrest secondary to suffocation. Cardiopulmonary resuscitation and surgical cricothyrotomy were performed, which restored his pulse and breathing. On day 5 of hospitalization, he underwent tracheotomy under inhibitor-neutralizing therapy, and we began emicizumab on day 19 of hospitalization to prevent further bleeding events. He recovered and was transferred to another hospital for rehabilitation on day 64 of hospitalization. CONCLUSIONS Because tongue hematomas progress dramatically within a few days, prompt airway maintenance by tracheotomy under appropriate hemostatic therapy must be considered. Furthermore, emicizumab induction after primary hemostasis prevents further bleeding. We suggest that initiating emicizumab therapy is a good choice to prevent further bleeding after critical bleeding events if the patient has not received the drug previously.
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http://dx.doi.org/10.12659/AJCR.916151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647615PMC
July 2019

Usefulness of the APTT waveform for the diagnosis of DIC and prediction of the outcome or bleeding risk.

Thromb J 2019 28;17:12. Epub 2019 Jun 28.

5Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie Japan.

Background: The usefulness of the activated partial thromboplastin time (APTT) waveform has been reported in hemophilia, acquired hemophilia and monitoring for anticoagulants.

Material And Methods: The APTT waveform was examined in patients suspected of having disseminated intravascular coagulation (DIC) to analyze its usefulness for the diagnosis of DIC or the prediction of the outcome or bleeding risk.

Results: DIC with fibrinogen < 2 g/L was frequently associated with infectious diseases (43.3%). The heights of the first derivative peak (1stDP) and second DP (2ndDP) were extremely low in DIC, especially DIC with hypofibrinogenemia, but high in infectious patients without DIC. The peak time and width of the 1stDP and 2ndDP were prolonged in patients with DIC. The heights of the 1DP and 2DP were markedly low in patients with a poor outcome or those with hemoglobin < 8.0 g/dl.

Discussion And Conclusion: As bleeding type DIC was observed in infectious DIC, DIC without hypofibrinogenemia might switch to DIC with hypofibrinogenemia by the progression of DIC. The height of the 1DP and 2DP is useful for the diagnosis of DIC and prediction of the bleeding risk or outcome.
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http://dx.doi.org/10.1186/s12959-019-0201-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598339PMC
June 2019

Successful Management of Immune Thrombocytopenia Presenting with Lethal Alveolar Hemorrhage.

Case Rep Hematol 2019 10;2019:5170282. Epub 2019 Jun 10.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu, Mie Prefecture 514-8507, Japan.

Immune thrombocytopenic purpura (ITP) typically presents with bleeding due to immunologic thrombocytopenia. Severe hemorrhage due to ITP is sometimes lethal, and the urgent recovery of platelets is necessary. In addition to conventional therapeutic strategies, romiplostim shows promising efficacy for chronic ITP. However, there is little evidence for the utilization of this treatment for acute ITP or acute exacerbation of chronic ITP. We report the case details of three elderly ITP patients presenting with lethal diffuse alveolar hemorrhage. These patients had the following underlying pulmonary diseases: case 1, nontuberculous mycobacterial infection and sarcoidosis; case 2, cryptogenic organizing pneumonia; case 3, pulmonary emphysema. These patients recovered following treatment with romiplostim at a higher dose (10 g/kg), in addition to conventional therapies including corticosteroids and high-dose intravenous immunoglobulin. In summary, the addition of romiplostim resulted in earlier recovery of thrombocytopenia than has been previously reported. Our three cases suggest that early romiplostim at a higher dose could be an efficacious therapeutic option for acute ITP patients with severe lethal bleeding.
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http://dx.doi.org/10.1155/2019/5170282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590510PMC
June 2019

Infiltrating CCR2 monocytes and their progenies, fibrocytes, contribute to colon fibrosis by inhibiting collagen degradation through the production of TIMP-1.

Sci Rep 2019 06 12;9(1):8568. Epub 2019 Jun 12.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.

Intestinal fibrosis is a serious complication in inflammatory bowel disease (IBD). Despite the remarkable success of recent anti-inflammatory therapies for IBD, incidence of intestinal fibrosis and need for bowel resection have not significantly changed. To clarify the contribution of haematopoietic-derived cells in intestinal fibrosis, we prepared bone marrow (BM) chimeric mice (chimeras), which were reconstituted with BM cells derived from enhanced green fluorescent protein (EGFP)-transgenic mice or CC chemokine receptor 2 (CCR2)-deficient mice. After 2 months of transplantation, BM chimeras were treated with azoxymethane/dextran sodium sulphate. During chronic inflammation, CCR2 BM-derived monocyte and fibrocyte infiltration into the colon and CC chemokine ligand 2 production increased, leading to colon fibrosis in EGFP BM chimeras. In CCR2-deficient BM chimeras, monocyte and fibrocyte numbers in the colonic lamina propria significantly decreased, and colon fibrosis was attenuated. In colon tissue, mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 but not of collagen I, transforming growth factor-β1 or matrix metalloproteinases was significantly different between the two chimeras. CCR2 monocytes and fibrocytes showed high Timp1 mRNA expression. Our results suggest that infiltrating CCR2 monocytes and their progenies, fibrocytes, promote colon fibrosis by inhibiting collagen degradation through TIMP-1 production.
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http://dx.doi.org/10.1038/s41598-019-45012-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562037PMC
June 2019

A population of CD20CD27CD43CD38 B1 cells in PNH are missing GPI-anchored proteins and harbor mutations.

Blood 2019 07 21;134(1):89-92. Epub 2019 May 21.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan; and.

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http://dx.doi.org/10.1182/blood.2019001343DOI Listing
July 2019

First Case of Cytokine Release Syndrome after Nivolumab for Gastric Cancer.

Case Rep Oncol 2019 Jan-Apr;12(1):147-156. Epub 2019 Feb 8.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan.

Introduction: Cytokine release syndrome (CRS) is a potentially life-threatening systemic disease that has been observed after treatment with antibodies and adoptive T cell therapies. In this case, we observed nivolumab-induced CRS in a patient with gastric cancer.

Case Presentation: A 43-year-old male with advanced gastric cancer was treated with nivolumab as a third-line chemotherapy. He had no history of allergies. Eight days after the first administration of nivolumab, fever, tachycardia, appetite loss and increases in liver and biliary enzymes were observed. Computed tomography revealed neither bile duct obstruction nor progression of liver metastases but showed that there was edema of the Gleason sheath. Histopathological analysis of the liver revealed cholestatic liver injury with CD8+ T lymphocyte and macrophage infiltration. Neither viral infection nor autoimmune disease was revealed. His symptoms were similar to those of CRS observed after T cell therapy. We diagnosed his disease as nivolumab-induced liver injury and cholangitis accompanied by CRS based on his serum cytokine levels.

Discussion/conclusion: To the best of our knowledge, this is the first report of nivolumab-induced CRS in a patient with gastric cancer.
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http://dx.doi.org/10.1159/000496933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477485PMC
February 2019

Evaluation of Medication Adherence and Pharmacokinetics of Dasatinib for Earlier Molecular Response in Japanese Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Pilot Study.

Ther Drug Monit 2019 10;41(5):575-581

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

Background: Tyrosine kinase inhibitors markedly improve the survival for patients with chronic myeloid leukemia (CML). However, a decrease in adherence leads to undesired therapeutic outcomes. In this study, the relationships among adherence, pharmacokinetics, response, and adverse effects for dasatinib treatment were prospectively investigated.

Methods: This study was a prospective cohort study of patients with newly diagnosed CML at 4 general hospitals and 1 university hospital. Patients started to receive dasatinib 100 mg once daily. A Medication Event Monitoring System was used to assess medication adherence and the medication possession ratio during the 12 months. Plasma concentrations of dasatinib were measured using liquid chromatograph-tandem mass spectrometry (LC-MS/MS), and therapy responses were assessed at 3, 6, and 12 months after treatment.

Results: Ten patients were included. An extremely high medication adherence for dasatinib was observed; the median medication possession ratio was 99.4%. All 9 CML patients with breakpoints in the major BCR-ABL achieved major molecular response (MMR; major BCR-ABL transcript level below 0.1% on the International Scale) within 12 months, and 5 achieved MMR within 6 months. The receiver operating characteristic curve analysis revealed that the cutoff value for the dasatinib area under the concentration-time curve was 336.1 ng × h/mL (accuracy 88.9%, sensitivity 80.0%, specificity 100%, and receiver operating characteristic curve-area under the concentration-time curve 0.800) for achieving MMR within 6 months. Two patients had interrupted dasatinib treatment because of pleural effusion and diarrhea with intestinal edema, respectively. These edematous adverse events developed after plasma dasatinib Cmin surpassed 3.0 ng/mL.

Conclusions: A Medication Event Monitoring System was applied for the direct evaluation of oral dasatinib adherence for the first time, and the clinical effect of dasatinib was investigated under the strict monitoring of patient adherence. Although this study had a small sample size, the plasma concentration monitoring of dasatinib is considered to be useful to predict an earlier molecular response with fewer edematous adverse events.
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http://dx.doi.org/10.1097/FTD.0000000000000639DOI Listing
October 2019

Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin.

Ann Hematol 2019 Jul 19;98(7):1647-1655. Epub 2019 Apr 19.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.
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http://dx.doi.org/10.1007/s00277-019-03689-9DOI Listing
July 2019
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