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Daratumumab and Nelarabine Treatment as Salvage Therapy for T-Lymphoblastic Lymphoma: A Case Report.
Gonzalo Castellanos, Laura Pardo, Alberto López, Javier Cornago, Jose Luis López, Alicia de Las Heras, Francisco J Díaz, Marta Martínez de Bourio, Eva Castillo, Pilar Llamas, Laura Solán
T-cell lymphoblastic lymphoma is an uncommon lymphoid neoplasm in adults, although more frequent in children and teenagers, that often affects the mediastinum and bone marrow, requiring intensive chemotherapy protocols. Its prognosis is poor if a cure is not achieved with first-line treatments. We present a case report of a 19-year-old man diagnosed with this type of lymphoma due to significant respiratory distress and a mediastinal mass. He received treatment according to the hyper-CVAD regimen, with a complete metabolic response...
February 24, 2024: Biomedicines
#2
Osamu Imataki, Haruyuki Fujita, Makiko Uemura
INTRODUCTION: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare subtype of T-cell leukemia that phenotypically expresses mature T-cell markers and immature myeloid markers such as CD33. Gemtuzumab ozogamicin (GO) is a novel agent for the CD33 molecular targeting antibody conjugated to the cytotoxic agent calicheamicin. GO is anticipated to be effective against ETP-ALL. In vivo studies promise antileukemic effects in cell lines; however, clinical reports to support this research are lacking...
2024: Case Reports in Oncology
#3
JOURNAL ARTICLE
Naokazu Nakamura, Chisaki Mizumoto, Akihiko Sugimoto, Masakazu Fujimoto, Takashi Ayaki, Akifumi Takaori-Kondo
T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has a poor prognosis. Nelarabine has recently shown relatively good results in patients with relapsed or refractory T-ALL/LBL, but requires careful monitoring for neurological complications. A 50-year-old man with early recurrence of T-LBL after allogenic peripheral blood stem cell transplantation received nelarabine monotherapy and achieved complete remission after 1 cycle. He then received umbilical cord blood transplantation, and experienced sustained disturbance of consciousness...
2024: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
#4
JOURNAL ARTICLE
Masato Yanagi, Makiko Mori, Mamoru Honda, Yuichi Mitani, Masafumi Seki, Kohei Fukuoka, Koichi Oshima, Yuki Arakawa, Katsuyoshi Koh
Therapy for relapsed or refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in children is challenging, and new treatment methods are needed. We retrospectively analyzed eight patients with r/r T-ALL (five patients) and T-LBL (three patients) who were treated with nelarabine (NEL) plus etoposide, cyclophosphamide, and intrathecal therapy, administered 3 days apart. Five patients achieved a complete response, and the other three achieved a partial response (PR)...
March 2024: International Journal of Hematology
#5
Poorva Vaidya, Huan-You Wang, Michelle D Don, Brian R Hinds, James K Mangan
Near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare hematologic malignancy, for which second line therapeutic options are limited. T-cell leukemias are also rarely associated with leukemia cutis, which is more often seen in leukemias of myeloid origin. We present the case of an adult male diagnosed with near ETP-ALL, with IDH2 and DNMT3A mutations, suggestive of a myeloid origin, and leukemia cutis. After the patient progressed on hyper-CVAD and nelarabine, we treated him with the BCL-2 inhibitor venetoclax and the hypomethylating agent decitabine...
2024: Leukemia Research Reports
#6
JOURNAL ARTICLE
U Karthik, J Motwani
INTRODUCTION: Nelarabine is now increasingly being used for the treatment of relapsed T-cell acute lymphoblastic leukemia/lymphoma, and about 18% of patients experience ≥ grade 3 toxicity. Despite the increasing use of this drug, there are no guidelines for managing its neurotoxicity. We would like to share our experience with one such case. CASE REPORT: A sixteen-year-old girl with T-lymphoblastic lymphoma received Nelarabine as part of her relapse treatment...
December 17, 2023: Journal of Oncology Pharmacy Practice
#7
JOURNAL ARTICLE
Marissa L Calbert, Gurushankar Chandramouly, Clare M Adams, Magali Saez-Ayala, Tatiana Kent, Mrityunjay Tyagi, V S S Abhinav Ayyadevara, Yifan Wang, John J Krais, John Gordon, Jessica Atkins, Monika M Toma, Stéphane Betzi, Andrew S Boghossian, Matthew G Rees, Melissa M Ronan, Jennifer A Roth, Aaron R Goldman, Nicole Gorman, Ramkrishna Mitra, Wayne E Childers, Xavier Graña, Tomasz Skorski, Neil Johnson, Christian Hurtz, Xavier Morelli, Christine M Eischen, Richard T Pomerantz
Anticancer nucleosides are effective against solid tumors and hematological malignancies, but typically are prone to nucleoside metabolism resistance mechanisms. Using a nucleoside-specific multiplexed high-throughput screening approach, we discovered 4'-ethynyl-2'-deoxycytidine (EdC) as a third-generation anticancer nucleoside prodrug with preferential activity against diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). EdC requires deoxycytidine kinase (DCK) phosphorylation for its activity and induced replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator...
December 8, 2023: Molecular Cancer Therapeutics
#8
JOURNAL ARTICLE
Xiaojiang Tang, Baohua Ping, Yang Liu, Yuhui Zhou
INTRODUCTION: Breast cancer remains the predominant cancer among females, accounting for about 24.2% of all cancer cases. Alarmingly, it is the primary cause of cancer-related mortality in women under 45. METHODS: This research analyzed RNA sequencing data from 1082 TCGA-BRCA and 107 GSE58812 breast cancer patients. Single-cell RNA data from five patients in the GSE118389 data set were also studied. Using Random forest and COX regression, we developed a prognostic model...
December 5, 2023: Environmental Toxicology
#9
Shunsuke Kimura, Petri Polonen, Lindsey Montefiori, Chun Shik Park, Ilaria Iacobucci, Allen Ej Yeoh, Andishe Attarbaschi, Andrew S Moore, Anthony Brown, Atsushi Manabe, Barbara Buldini, Burgess B Freeman, Chelsey Chen, Cheng Cheng, Chiew Kean Hui, Chi-Kong Li, Ching-Hon Pui, Chunxu Qu, Daisuke Tomizawa, David T Teachey, Elena Varotto, Elisabeth M Paietta, Elizabeth D Arnold, Franco Locatelli, Gabriele Escherich, Hannah Elisa Muhle, Hanne Vibeke Marquart, Hester A de Groot-Kruseman, Jacob M Rowe, Jan Stary, Jan Trka, John Kim Choi, Jules P P Meijerink, Jun J Yang, Junko Takita, Katarzyna Pawinska-Wasikowska, Kathryn G Roberts, Katie Han, Kenneth J Caldwell, Kjeld Schmiegelow, Kristine R Crews, Mariko Eguchi, Martin Schrappe, Martin Zimmerman, Masatoshi Takagi, Mellissa Maybury, Michael Svaton, Michaela Reiterova, Michal Kicinski, Mollie S Prater, Motohiro Kato, Noemi Reyes, Orietta Spinelli, Paul Thomas, Pauline Mazilier, Qingsong Gao, Riccardo Masetti, Rishi S Kotecha, Rob Pieters, Sarah Elitzur, Selina M Luger, Sharnise Mitchell, Shondra M Pruett-Miller, Shuhong Shen, Sima Jeha, Stefan Köhrer, Steven M Kornblau, Szymon Skoczeń, Takako Miyamura, Tiffaney L Vincent, Toshihiko Imamura, Valentino Conter, Yanjing Tang, Yen-Chun Liu, Yunchao Chang, Zhaohui Gu, Zhongshan Cheng, Zhou Yinmei, Hiroto Inaba, Charles G Mullighan
PURPOSE: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease. METHODS: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing. Experimental modeling was used to examine the mechanistic impacts of genomic alterations...
November 8, 2023: medRxiv
#10
JOURNAL ARTICLE
Diane Ito, Chaoling Feng, Christine Fu, Chong Kim, James Wu, David Dalton, Josh Epstein, Julia T Snider, Adam S DuVall
PURPOSE: Although immunotherapies such as blinatumomab and inotuzumab have led to improved outcomes, financial burden and health resource utilization (HRU) have increased for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). This study assessed real-world HRU and costs of care among adult patients with R/R B-ALL by line of therapy (LoT) in the United States. METHODS: We selected patients from the MarketScanⓇ Database (January 1, 2016 through December 31, 2020) as follows: ≥1 claims of ALL-indicated first-line (1L) therapies, ≥1 diagnosis of ALL before the index date (1L initiation date), 6-month continuous enrollment before the index date, second-line (2L) therapy initiation, ≥18 years old at 2L, no clinical trial enrollment, no diagnosis of other forms of non-Hodgkin's lymphoma, and no claim for daratumumab or nelarabine during the study period...
November 17, 2023: Clinical Therapeutics
#11
REVIEW
Lane H Miller, Kim L Maxa, Stuart S Winter, Nathan P Gossai
INTRODUCTION: Nelarabine is a guanine nucleoside analog and functions to terminate DNA synthesis in dividing cells. Pre-clinical and clinical studies have shown that it preferentially accumulates in T-cells where it exerts its cytotoxic effects. After generations of treatment protocol advances, it has been incorporated into numerous treatment regimens against T-lineage acute lymphoblastic leukemia/lymphoma (T-ALL/LLy). On 8 March 2023, the FDA approved the use of nelarabine for its use in T-ALL due to clear evidence of clinical benefits...
2023: Expert Review of Anticancer Therapy
#12
REVIEW
Sima Jeha
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. The T-cell subtype (T-ALL) accounts for 10-15% of pediatric ALL cases and has been historically associated with outcomes inferior to those of B-cell ALL (B-ALL). The prognosis of T-ALL has significantly improved with contemporary intensive pediatric regimens. However, most children with relapsed T-ALL have dismal outcomes and fewer therapeutic salvage options than those available for B-ALL. After demonstrating efficacy in relapsed T-ALL, nelarabine is being increasingly incorporated into frontline T-ALL regimens...
August 29, 2023: Indian Journal of Pediatrics
#13
JOURNAL ARTICLE
Daiki Mukai, Naonori Harada, Ikumi Shibano, Yusuke Kizawa, Hiroshi Shiragami, Atsuko Mugitani, Masayuki Hino
No abstract text is available yet for this article.
August 2023: EJHaem
#14
JOURNAL ARTICLE
Yanjie Yi, Urvi Zankharia, Joel A Cassel, Fang Lu, Joseph M Salvino, Paul M Lieberman, Ronald G Collman
HIV-infected macrophages are long-lived cells that represent a barrier to functional cure. Additionally, low-level viral expression by central nervous system (CNS) macrophages contributes to neurocognitive deficits that develop despite antiretroviral therapy (ART). We recently identified H3K9me3 as an atypical epigenetic mark associated with chronic HIV infection in macrophages. Thus, strategies are needed to suppress HIV-1 expression in macrophages, but the unique myeloid environment and the responsible macrophage/CNS-tropic strains require cell/strain-specific approaches...
August 14, 2023: Journal of Virology
#15
JOURNAL ARTICLE
Hongjin Wang, Nian Wang, Ze Tang, Qiuyu Liu, Shiyu Nie, Wu Tao
BACKGROUND: The study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC). METHODS: We downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model...
July 18, 2023: Hereditas
#16
REVIEW
Shai Shimony, Daniel J DeAngelo, Marlise R Luskin
T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma (T-ALL/LBL) is a rare hematologic malignancy most commonly affecting adolescent and young adult males. Outcomes are dismal for patients who relapse, thus, improvement in treatment is needed. Nelarabine, a prodrug of the deoxyguanosine analog 9-β-arabinofuranosylguanine, is uniquely toxic to T lymphoblasts, compared with B lymphoblasts and normal lymphocytes, and has been developed for the treatment of T-ALL/LBL. Based on phase 1 and 2 trials in children and adults, single-agent nelarabine is approved for treatment of patients with relapsed or refractory T-ALL/LBL, with the major adverse effect being central and peripheral neurotoxicity...
January 9, 2024: Blood Advances
#17
JOURNAL ARTICLE
Yanlin Wu, Zhengjun Lin, Xianzhe Tang, Zhongyi Tong, Yuqiao Ji, Yingting Xu, Ziting Zhou, Jing Yang, Zhihong Li, Tang Liu
BACKGROUND: Hypermethylated in Cancer 1 (HIC1) was originally confirmed as a tumor suppressor and has been found to be hypermethylated in human cancers. Although growing evidence has supported the critical roles of HIC1 in cancer initiation and development, its roles in tumor immune microenvironment and immunotherapy are still unclear, and no comprehensive pan-cancer analysis of HIC1 has been conducted. METHODS: HIC1 expression in pan-cancer, and differential HIC1 expression between tumor and normal samples were investigated...
2023: Frontiers in Immunology
#18
COMMENT
Niharendu Ghara, Vaskar Saha
No abstract text is available yet for this article.
June 2023: Lancet Haematology
#19
RANDOMIZED CONTROLLED TRIAL
Atsushi Sato, Yoshihiro Hatta, Chihaya Imai, Koichi Oshima, Yasuhiro Okamoto, Takao Deguchi, Yoshiko Hashii, Takashi Fukushima, Toshinori Hori, Nobutaka Kiyokawa, Motohiro Kato, Shoji Saito, Kenichi Anami, Tatsuhiro Sakamoto, Yoshiyuki Kosaka, Souichi Suenobu, Toshihiko Imamura, Akiko Kada, Akiko M Saito, Atsushi Manabe, Hitoshi Kiyoi, Itaru Matsumura, Katsuyoshi Koh, Arata Watanabe, Yasushi Miyazaki, Keizo Horibe
BACKGROUND: T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. METHODS: In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group...
June 2023: Lancet Haematology
#20
REVIEW
Janisha Patel, Xueliang Gao, Haizhen Wang
Current therapies for T-cell acute leukemia are based on risk stratification and have greatly improved the survival rate for patients, but mortality rates remain high owing to relapsed disease, therapy resistance, or treatment-related toxicities/infection. Patients with relapsed disease continue to have poor outcomes. In the past few years, newer agents have been investigated to optimize upfront therapies for higher-risk patients in the hopes of decreasing relapse rates. This review summarizes the progress of chemo/targeted therapies using Nelarabine/Bortezomib/CDK4/6 inhibitors for T-ALL in clinical trials and novel strategies to target NOTCH-induced T-ALL...
April 13, 2023: International Journal of Molecular Sciences
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