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Acute Lymphoblastic leukemia in adults

Qiuyun Fang, Tian Yuan, Yan Li, Juan Feng, Xiaoyuan Gong, Qinghua Li, Xingli Zhao, Kaiqi Liu, Kejing Tang, Zheng Tian, Qi Zhang, Ying Wang, Bingcheng Liu, Min Wang, Kun Ru, Jianxiang Wang, Yingchang Mi
The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 ( IKZF1 ), paired box 5 ( PAX5 ), ETS variant 6 ( ETV6 ), RB transcriptional corepressor 1 ( RB1 ), BTG anti-proliferation factor 1 ( BTG1 ), early B-cell factor 1 ( EBF1 ), cyclin dependent kinase inhibitor 2A/2B ( CDKN2A/2B ) and cytokine receptor like factor 2 ( CRLF2 ) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed...
April 2018: Oncology Letters
Maria Maruffi, Richard Sposto, Matthew J Oberley, Lynn Kysh, Etan Orgel
The rarity of mixed-phenotype acute leukemia (MPAL) has resulted in diffuse literature consisting of small case series, thus precluding a consensus treatment approach. We conducted a meta-analysis and systematic review to investigate the association of treatment type (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], or "hybrid" regimens), disease response, and survival. We searched seven databases from inception through June 2017 without age or language restriction. Included studies reported sufficient treatment detail for de novo MPAL classified according to the well-established European Group for Immunological Characterization of Acute Leukemias (EGIL) or World Health Organization (WHO2008) criteria...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Reibán-Espinoza Esteban, Bourlon Christianne, Aguayo Alvaro, Demichelis-Gómez Roberta
INTRODUCTION: The expression of the CD20 on adult B-cell acute lymphoblastic leukemia (ALL-B) has generally been associated with a poor prognosis, and several studies have explored the incorporation of rituximab into the therapeutic regimen for adult ALL-B patients, with a positive effect on event-free survival (EFS). PATIENTS AND METHODS: We analyzed the prognostic value of CD20 expression and the effect of rituximab for the treatment of Hispanic adult ALL-B patients...
February 26, 2018: Clinical Lymphoma, Myeloma & Leukemia
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
Rene Marke, Frank N van Leeuwen, Blanca Scheijen
Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 gene defects are associated with inferior treatment outcome in both childhood and adult BCP-ALL and occur in more than 70% of BCR-ABL1 positive and BCR-ABL1-like ALL cases. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome...
March 8, 2018: Haematologica
Ping-Pin Zheng, Johan M Kros, Jin Li
Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah™ and Yescarta™) were recently approved by the FDA. Kymriah™ for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta™ for the treatment of adult patients with R/R large B cell lymphoma. In common, both drugs are CD19-specific CAR T cell therapies lysing CD19-positive targets. Their dramatic efficacy in the short term has been highlighted by many media reports...
March 1, 2018: Drug Discovery Today
Lia Gore, Pamela R Kearns, Maria Lucia de Martino Lee, Carmino Antonio De Souza, Yves Bertrand, Nobuko Hijiya, Linda C Stork, Nack-Gyun Chung, Rocio Cardenas Cardos, Tapan Saikia, Franca Fagioli, Jong Jin Seo, Judith Landman-Parker, Donna Lancaster, Andrew E Place, Karen R Rabin, Mariana Sacchi, Rene Swanink, C Michel Zwaan
Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome-positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients < 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension...
March 2, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Manman Deng, Jie Zha, Zhiwu Jiang, Xian Jia, Yuanfei Shi, Peng Li, Xiao Lei Chen, Zhihong Fang, Zhiqiang Du, Bing Xu
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature B or T lymphocytes. Extensive studies have suggested an involvement of angiogenesis signaling in ALL progression and resistance to treatment. Thus, targeting angiogenesis with anti-angiogenic drugs may be a promising approach for ALL treatment. In this study, we investigated the effectiveness of Apatinib, a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2 in ALL cells...
February 28, 2018: Journal of Translational Medicine
Jae H Park, F Andres Romero, Ying Taur, Michel Sadelain, Renier J Brentjens, Tobias M Hohl, Susan K Seo
Background: Chimeric antigen receptor (CAR)-modified T cells that target the CD19 antigen present a novel promising therapy for the treatment of relapsed B-cell acute lymphoblastic leukemia (ALL). Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant non-infectious complications of CD19 CAR T cell therapy, infections associated with this treatment modality have not been well documented. Methods: We analyzed infectious complications that followed CD19 CAR T cell therapy in 53 adult patients with relapsed ALL enrolled in a phase I clinical trial at Memorial Sloan Kettering Cancer Center (NCT01044069)...
February 22, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
(no author information available yet)
Two studies reported durable long-term remissions in patients with acute lymphoblastic leukemia treated with CAR T-cell therapies. One study focused on children and young adults treated with tisagenlecleucel; the other focused on adults who received infusions of 19-28z CAR T cells.
February 22, 2018: Cancer Discovery
Moran Gotesman, Thanh-Trang T Vo, Lee-Or Herzog, Tiffeny Tea, Sharmila Mallya, Sarah K Tasian, Marina Konopleva, David A Fruman
High-risk subtypes of B-cell acute lymphoblastic leukemia (B-ALL) include Philadelphia chromosome-positive (Ph+) B-ALL driven by the BCR-ABL1 oncogene and a more recently identified subtype known as BCR-ABL -like or Ph-like B-ALL. A hallmark of both Ph+ and Ph-like B-ALL is constitutive activation of tyrosine kinase signaling that is potentially targetable with tyrosine kinase inhibitors (TKIs). B-ALL cells also receive extracellular signals from the microenvironment that can maintain proliferation and survival following treatment with TKIs...
January 19, 2018: Oncotarget
Megan Romeo, Tetiana Hutchison, Aditi Malu, Averi White, Janice Kim, Rachel Gardner, Katie Smith, Katherine Nelson, Rachel Bergeson, Ryan McKee, Carolyn Harrod, Lee Ratner, Bernhard Lüscher, Ernest Martinez, Robert Harrod
In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression...
February 17, 2018: Virology
Nivedita Patni, Xilong Li, Beverley Adams-Huet, Abhimanyu Garg
BACKGROUND: Extreme hypertriglyceridemia (eHTG; serum triglycerides ≥ 2000 mg/dL) poses a significant risk for acute pancreatitis. There is paucity of data regarding the prevalence and etiology of eHTG in children. OBJECTIVE: To determine the prevalence, clinical features and etiologies of patients with eHTG at a tertiary children's hospital in the United States and in the United States National Health and Nutrition Examination Survey (NHANES). METHODS: A retrospective analysis was conducted of the electronic medical records of the Children's Medical Center, Dallas, from 2000-2015, and the NHANES data from 2005-2014 for eHTG...
January 12, 2018: Journal of Clinical Lipidology
Stuart E Siegel, Wendy Stock, Rebecca H Johnson, Anjali Advani, Lori Muffly, Dan Douer, Damon Reed, Mark Lewis, David R Freyer, Bijal Shah, Selina Luger, Brandon Hayes-Lattin, Jerry J Jaboin, Peter F Coccia, Daniel J DeAngelo, Nita Seibel, Archie Bleyer
Importance: The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL...
February 15, 2018: JAMA Oncology
Victor M Orellana-Noia, Michael G Douvas
PURPOSE OF REVIEW: Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years...
February 14, 2018: Current Hematologic Malignancy Reports
Francine Marie Foss, Terri Parker
LESSONS LEARNED: Clofarabine can be active in relapsed and refractory lymphoid malignancies on a weekly dosing schedule.Responses were seen in patients with T-cell lymphomas, including cutaneous T-cell lymphoma, but not in patients with aggressive B-cell lymphomas. BACKGROUND: Clofarabine is a second-generation purine nucleoside analog currently approved for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. In adults, clofarabine has been investigated in several phase I and II trials as a single agent and in combination for relapsed or refractory acute leukemia...
February 7, 2018: Oncologist
Rachael R Schulte, Manasi V Madiwale, Allyson Flower, Jessica Hochberg, Michael J Burke, Jennifer L McNeer, Adam DuVall, Archie Bleyer
Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy...
February 12, 2018: Leukemia & Lymphoma
Elysia Alvarez, Lori Muffly, Qian Li, Ann Brunson, Ted Wun, Lisa Chamberlain, Theresa Keegan
No abstract text is available yet for this article.
February 9, 2018: Leukemia & Lymphoma
Nicholas J Short, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi
PURPOSE OF REVIEW: Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population. RECENT FINDINGS: The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths...
February 8, 2018: Current Hematologic Malignancy Reports
Laurie Freire Boullosa, Payalben Savaliya, Stephanie Bonney, Laurence Orchard, Hannah Wickenden, Cindy Lee, Evelien Smits, Alison H Banham, Ken I Mills, Kim Orchard, Barbara-Ann Guinn
B-cell acute lymphoblastic leukemia (B-ALL) is a rare heterogeneous disease characterized by a block in lymphoid differentiation and a rapid clonal expansion of immature, non-functioning B cells. Adult B-ALL patients have a poor prognosis with less than 50% chance of survival after five years and a high relapse rate after allogeneic haematopoietic stem cell transplantation. Novel treatment approaches are required to improve the outcome for patients and the identification of B-ALL specific antigens are essential for the development of targeted immunotherapeutic treatments...
January 9, 2018: Oncotarget
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