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Journal of Hematology & Oncology

Bixia Tang, Xieqiao Yan, Xinan Sheng, Lu Si, Chuanliang Cui, Yan Kong, Lili Mao, Bin Lian, Xue Bai, Xuan Wang, Siming Li, Li Zhou, Jiayi Yu, Jie Dai, Kai Wang, Jinwei Hu, Lihou Dong, Haifeng Song, Hai Wu, Hui Feng, Sheng Yao, Zhihong Chi, Jun Guo
BACKGROUND: JS001, a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor, blocks the interaction of PD-1 with its ligands and promotes T cell activation in preclinical studies. This phase I study is designed to evaluate the safety, tolerability, and clinical activity of JS001 in advanced melanoma or urologic cancer patients who are refractory to standard systemic therapy. PATIENTS AND METHODS: In the dose escalation cohorts, subjects initially received a single-dose, intravenous infusion of JS001, and were followed for 28 days followed by multi-dose infusions every 2 weeks...
January 14, 2019: Journal of Hematology & Oncology
Yongkun Sun, Lin Yang, Xuezhi Hao, Yutao Liu, Jinwen Zhang, Zhiqiang Ning, Yuankai Shi
BACKGROUND: Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα, and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF-1R. This phase I dose-escalation study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor activity of chiauranib in patients with refractory advanced solid tumor and lymphoma. METHODS: Eighteen patients were treated with continuous dosing of chiauranib from 10 to 65 mg once daily in a dose-escalation 3 + 3 design and evaluated in 28-day cycles...
January 14, 2019: Journal of Hematology & Oncology
Alva Rani James, Michael P Schroeder, Martin Neumann, Lorenz Bastian, Cornelia Eckert, Nicola Gökbuget, Jutta Ortiz Tanchez, Cornelia Schlee, Konstandina Isaakidis, Stefan Schwartz, Thomas Burmeister, Arend von Stackelberg, Michael A Rieger, Stefanie Göllner, Martin Horstman, Martin Schrappe, Renate Kirschner-Schwabe, Monika Brüggemann, Carsten Müller-Tidow, Hubert Serve, Altuna Akalin, Claudia D Baldus
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes of B cell acute lymphoblastic leukemia (BCP-ALL) have not yet been investigated. Here, we assess to what extent lncRNA expression and DNA methylation is driving the progression of relapsed BCP-ALL subtypes and we determine if the expression and DNA methylation profile of lncRNAs correlates with established BCP-ALL subtypes...
January 14, 2019: Journal of Hematology & Oncology
Narendranath Epperla, Kwang W Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard Hildebrandt, David Inwards, Mohamed A Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R Rezvani, Rizwan Romee, Nirav N Shah, Ana Sureda, Timothy S Fenske, Mehdi Hamadani
BACKGROUND: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT. METHODS: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000-2016. RESULTS: The median patient age was 56 years (range = 21-77). Majority of the patients were Caucasians (86%), with a male predominance (60%)...
January 10, 2019: Journal of Hematology & Oncology
Mu Xu, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Xueni Xu, Bei Pan, Tao Xu, Li Sun, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang
BACKGROUND: Abnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets. METHODS: We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer (CRC). The functions of small nucleolar RNA host gene 6 (SNHG6) were investigated through in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, wound healing assay, transwell assay, and xenograft model)...
January 9, 2019: Journal of Hematology & Oncology
Ilaria Saltarella, Fortunato Morabito, Nicola Giuliani, Carolina Terragna, Paola Omedè, Antonio Palumbo, Sara Bringhen, Lorenzo De Paoli, Enrica Martino, Alessandra Larocca, Massimo Offidani, Francesca Patriarca, Chiara Nozzoli, Tommasina Guglielmelli, Giulia Benevolo, Vincenzo Callea, Luca Baldini, Mariella Grasso, Giovanna Leonardi, Manuela Rizzo, Antonietta Pia Falcone, Daniela Gottardi, Vittorio Montefusco, Pellegrino Musto, Maria Teresa Petrucci, Franco Dammacco, Mario Boccadoro, Angelo Vacca, Roberto Ria
BACKGROUND: Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis...
January 9, 2019: Journal of Hematology & Oncology
Yi Rang Kim, Jung Ki Yoo, Chang Wook Jeong, Jin Woo Choi
The original article [1] contains an inadvertent omission in the Funding declaration.
January 9, 2019: Journal of Hematology & Oncology
Stefania Raimondo, Laura Saieva, Emanuela Vicario, Marzia Pucci, Denise Toscani, Mauro Manno, Samuele Raccosta, Nicola Giuliani, Riccardo Alessandro
BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with osteolytic bone disease. Recently, the role of MM-derived exosomes in the osteoclastogenesis has been demonstrated although the underlying mechanism is still unknown. Since exosomes-derived epidermal growth factor receptor ligands (EGFR) are involved in tumor-associated osteolysis, we hypothesize that the EGFR ligand amphiregulin (AREG) can be delivered by MM-derived exosomes and participate in MM-induced osteoclastogenesis...
January 8, 2019: Journal of Hematology & Oncology
Kamal Chamoun, Hagop Kantarjian, Rami Atallah, Graciela Nogueras Gonzalez, Ghayas C Issa, Mary Beth Rios, Guillermo Garcia-Manero, Gautam Borthakur, Farhad Ravandi, Nitin Jain, Naval Daver, Marina Konopleva, Courtney D DiNardo, Tapan Kadia, Naveen Pemmaraju, Elias Jabbour, Jorge Cortes
BACKGROUND: Patients with CML treated with TKI can have a life expectancy comparable to that of the general population. Due to the extended duration of TKI administration, treatment discontinuation has been increasingly sought. METHODS: Medical records of 100 patients with CML who were in MR4.5 and discontinued their TKI outside clinical trials were reviewed. RESULTS: After a median follow-up of 30 months (range, 5-112 months) after discontinuation, 35% and 17% lost MR4...
January 3, 2019: Journal of Hematology & Oncology
Jorge E Cortes, Jane F Apperley, Daniel J DeAngelo, Michael W Deininger, Vamsi K Kota, Philippe Rousselot, Carlo Gambacorti-Passerini
Bosutinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI), has been available for several years as a treatment for chronic-, accelerated-, and blast-phase chronic myeloid leukemia (CML), for patients with resistance or intolerance to prior therapy. In 2017, the BFORE trial demonstrated efficacy of bosutinib as first-line treatment in adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). The most common adverse events (AEs) of any grade in bosutinib-treated patients in BFORE were diarrhea, nausea, thrombocytopenia, increased alanine aminotransferase, and increased aspartate aminotransferase, consistent with the most commonly reported AEs in earlier studies...
December 27, 2018: Journal of Hematology & Oncology
Zihai Li, Wenru Song, Mark Rubinstein, Delong Liu
The immune system is the hard-wired host defense mechanism against pathogens as well as cancer. Five years ago, we pondered the question if the era of cancer immunotherapy was upon us (Li et al., Exp Hem Oncol 2013). Exciting progresses have been made at all fronts since then, including (1) sweeping approval of six agents by the US Food and Drug Administration (FDA) to block the PD-1/PD-L1 pathway for treatment of 13 cancer types; (2) a paradigm shifting indication of PD-1 and CTLA4 blockers for the management of a broad class of cancers with DNA mismatch repair defect, the first-ever tissue agnostic approval of cancer drugs; (3) real world practice of adoptive T cell therapy with two CD19-directed chimeric antigen receptor T cell products (CAR-T) for relapsed and/or refractory B cell malignancies including acute lymphoid leukemia and diffuse large B cell lymphoma, signaling the birth of a field now known as synthetic immunology; (4) the award of 2018 Nobel Prize in Physiology and Medicine from the Nobel Committee to Tasuku Honjo and James Allison "for their discovery of cancer medicine by inhibition of negative immune regulation" ( www...
December 21, 2018: Journal of Hematology & Oncology
Wan-Hong Zhao, Jie Liu, Bai-Yan Wang, Yin-Xia Chen, Xing-Mei Cao, Yun Yang, Yi-Lin Zhang, Fang-Xia Wang, Peng-Yu Zhang, Bo Lei, Liu-Fang Gu, Jian-Li Wang, Nan Yang, Ru Zhang, Hui Zhang, Ying Shen, Ju Bai, Yan Xu, Xu-Geng Wang, Rui-Li Zhang, Li-Li Wei, Zong-Fang Li, Zhen-Zhen Li, Yan Geng, Qian He, Qiu-Chuan Zhuang, Xiao-Hu Fan, Ai-Li He, Wang-Gang Zhang
BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM...
December 20, 2018: Journal of Hematology & Oncology
Seok Jin Kim, Sang Eun Yoon, Won Seog Kim
Extranodal natural killer/T cell lymphoma (ENKTL), nasal type, presents predominantly as a localized disease involving the nasal cavity and adjacent sites, and the treatment of localized nasal ENKTL is a major issue. However, given its rarity, there is no standard therapy based on randomized controlled trials and therefore a lack of consensus on the treatment of localized nasal ENKTL. Currently recommended treatments are based mainly on the results of phase II studies and retrospective analyses. Because the previous outcomes of anthracycline-containing chemotherapy were poor, non-anthracycline-based chemotherapy regimens, including etoposide and L-asparaginase, have been used mainly for patients with localized nasal ENKTL...
December 20, 2018: Journal of Hematology & Oncology
Wei Jiang, Tiancong He, Shuai Liu, Yingying Zheng, Libing Xiang, Xuan Pei, Ziliang Wang, Huijuan Yang
BACKGROUND: The study aims to present the effect of PIK3CA E542K and E545K mutations on glucose metabolism and proliferation and identify their underlying mechanisms in cervical cancer. METHODS: The maximum standard uptake value (SUVmax ) of tumors was detected by18 F-FDG PET/CT scan. In vitro, glycolysis analysis, extracellular acidification rate analysis, and ATP production were used to evaluate the impact of PIK3CA E542K and E545K mutations on glucose metabolism...
December 14, 2018: Journal of Hematology & Oncology
Benoît Tessoulin, Agnès Moreau-Aubry, Géraldine Descamps, Patricia Gomez-Bougie, Sophie Maïga, Alban Gaignard, David Chiron, Emmanuelle Ménoret, Steven Le Gouill, Philippe Moreau, Martine Amiot, Catherine Pellat-Deceunynck
BACKGROUND: Human myeloma cell lines (HMCLs) are widely used for their representation of primary myeloma cells because they cover patient diversity, although not fully. Their genetic background is mostly undiscovered, and no comprehensive study has ever been conducted in order to reveal those details. METHODS: We performed whole-exon sequencing of 33 HMCLs, which were established over the last 50 years in 12 laboratories. Gene expression profiling and drug testing for the 33 HMCLs are also provided and correlated to exon-sequencing findings...
December 13, 2018: Journal of Hematology & Oncology
Delong Liu, Dhruv Mehta, Supreet Kaur, Arun Kumar, Kaushal Parikh, Lavneet Chawla, Shanti Patel, Amirta Devi, Aparna Saha
BACKGROUND: There is no convincing data on the trends of hospitalizations, mortality, cost, and demographic variations associated with inpatient admissions for gastric cancer in the USA. The aim of this study was to use a national database of US hospitals to evaluate the trends associated with gastric cancer. METHODS: We analyzed the National Inpatient Sample (NIS) database for all patients in whom gastric cancer (ICD-9 code: 151.0, 151.1, 151.2, 151.3, 151.4, 151...
December 13, 2018: Journal of Hematology & Oncology
Man Hu, Liyang Jiang, Xiangli Cui, Jianguang Zhang, Jinming Yu
Precision radiotherapy, which accurately delivers the dose on a tumor and confers little or no irradiation to the surrounding normal tissue and organs, results in maximum tumor control and decreases the toxicity to the utmost extent. Proton beam therapy (PBT) provides superior dose distributions and has a dosimetric advantage over photon beam therapy. Initially, the clinical practice and study of proton beam therapy focused on ocular tumor, skull base, paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas, which responded poorly when treated with photon radiotherapy...
December 12, 2018: Journal of Hematology & Oncology
Peilong Lai, Xiaomei Chen, Liyan Guo, Yulian Wang, Xialin Liu, Yan Liu, Tian Zhou, Tian Huang, Suxia Geng, Chengwei Luo, Xin Huang, Suijing Wu, Wei Ling, Xin Du, Chang He, Jianyu Weng
BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising therapy for preventing chronic Graft-Versus-Host Disease (cGVHD) due to their potent immunomodulatory properties. However, the safety concerns regarding the use of MSCs remain unsolved, and conflicting effects are observed due to the heterogeneity of MSCs. Recently, exosomes were shown to mediate the paracrine effects of MSCs, making it a potential candidate for cell-free therapies. The aim of this study is to investigate the efficacy and safety of MSCs-derived exosomes (MSCs-exo) in an established cGVHD mouse model...
December 7, 2018: Journal of Hematology & Oncology
Mei Wu, Chuntuan Li, Xiongpeng Zhu
FLT3 mutations are one of the most common findings in acute myeloid leukemia (AML). FLT3 inhibitors have been in active clinical development. Midostaurin as the first-in-class FLT3 inhibitor has been approved for treatment of patients with FLT3-mutated AML. In this review, we summarized the preclinical and clinical studies on new FLT3 inhibitors, including sorafenib, lestaurtinib, sunitinib, tandutinib, quizartinib, midostaurin, gilteritinib, crenolanib, cabozantinib, Sel24-B489, G-749, AMG 925, TTT-3002, and FF-10101...
December 4, 2018: Journal of Hematology & Oncology
Jie Xiong, Wei-Li Zhao
Natural-killer/T cell lymphoma (NKTCL) represents the most common subtype of extranodal lymphoma with aggressive clinical behavior. Prevalent in Asians and South Americans, the pathogenesis of NKTCL remains to be fully elucidated. Using system biology techniques including genomics, transcriptomics, epigenomics, and metabolomics, novel biomarkers and therapeutic targets have been revealed in NKTCL. Whole-exome sequencing studies identify recurrent somatic gene mutations, involving RNA helicases, tumor suppressors, JAK-STAT pathway molecules, and epigenetic modifiers...
December 4, 2018: Journal of Hematology & Oncology
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