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Acute Lymphoblastic leukemia in adults

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https://www.readbyqxmd.com/read/29155426/cd22-targeted-car-t-cells-induce-remission-in-b-all-that-is-naive-or-resistant-to-cd19-targeted-car-immunotherapy
#1
Terry J Fry, Nirali N Shah, Rimas J Orentas, Maryalice Stetler-Stevenson, Constance M Yuan, Sneha Ramakrishna, Pamela Wolters, Staci Martin, Cindy Delbrook, Bonnie Yates, Haneen Shalabi, Thomas J Fountaine, Jack F Shern, Robbie G Majzner, David F Stroncek, Marianna Sabatino, Yang Feng, Dimiter S Dimitrov, Ling Zhang, Sang Nguyen, Haiying Qin, Boro Dropulic, Daniel W Lee, Crystal L Mackall
Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy...
November 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29149251/parental-age-and-risk-of-lymphoid-neoplasms
#2
Gunnar Larfors, Ingrid Glimelius, Sandra Eloranta, Karin E Smedby
High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29121606/pattern-of-hematological-malignancies-in-adolescents-and-young-adults-in-bangladesh
#3
Md Mahbub Hasan, Enayetur Raheem, Tanvira Afroze Sultana, Mohammad Sorowar Hossain
INTRODUCTION: The adolescent and young adult (AYA) age group (15-39 years) bears distinct characteristics in terms of cancer biology, long-term health and treatment-related complications and psychosocial aspects. The overall scenario of cancer including hematological malignancies (HMs) is largely unknown in Bangladesh, where a significant proportion of people (44% of total population) belong to AYA age group. This study aims to describe the patterns of HM among AYA in the context of Bangladesh METHODS: Two previously published datasets (on hematological malignancies and childhood and adolescent cancer) were merged to construct a comprehensive dataset focusing exclusively on HMs in AYA age group...
November 6, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/29092647/inotuzumab-ozogamicin-for-the-treatment-of-acute-lymphoblastic-leukemia
#4
Ariella Tvito, Jacob M Rowe
Acute lymphoblastic leukemia (ALL) is an uncommon disorder that affects about 20% of adults with acute leukemia. Historically, those who relapse from this condition have a dismal prognosis. Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. One recent development is the FDA approved therapy inotuzumab ozogamicin which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease...
November 1, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29082835/efficacy-and-safety-of-bispecific-t-cell-engager-blinatumomab-and-the-potential-to-improve-leukemia-free-survival-in-b-cell-acute-lymphoblastic-leukemia
#5
Josep-Maria Ribera
Immunotherapy is a promising modality of treatment of neoplastic diseases, including acute lymphoblastic leukemia (ALL). The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody blinatumomab can transiently bind cytotoxic T cells to CD19(+) target B cells of ALL inducing their serial lysis. Areas covered: This review focuses on the efficacy and safety of blinatumomab used for the treatment of relapsed/refractory (R/R) ALL and minimal residual disease (MRD)-positive B-cell precursor (BCP) ALL in adults and children, as well as the future prospects of this drug in the treatment of ALL...
October 30, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29076004/high-mtor-expression-independently-prognosticates-poor-clinical-outcome-to-induction-chemotherapy-in-acute-lymphoblastic-leukemia
#6
Asheema Khanna, Bharat Bhushan, Pradeep Singh Chauhan, Sunita Saxena, Dipendra Kumar Gupta, Fouzia Siraj
In acute lymphoblastic leukemia (ALL), limited data are available on mTOR gene expression in clinical samples and its role in predicting response to induction chemotherapy. mRNA expression of mTOR gene was determined quantitatively by real-time PCR in 50 ALL patients (30 B-ALL and 20 T-ALL) and correlated with clinical outcome after induction chemotherapy. Expression level of mTOR was upregulated in more than 50% of cases of ALL. In T-ALL, high expression of mTOR was commonly seen, more in adults than children (82 vs...
October 26, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29068867/low-expression-of-mir-18a-as-a-characteristic-of-pediatric-acute-lymphoblastic-leukemia
#7
Neda Mosakhani, Mohamed El Missiry, Emmi Vakkila, Sakari Knuutila, Jukka Vakkila
BACKGROUND: Acute lymphoblastic leukemia (ALL) occurs in both adults and children but the response to chemotherapy and survival is significantly worse in the adults. We aimed to study whether the expression of immune system-associated miRNAs would differ between adult and pediatric patients with ALL at the time of diagnosis. MATERIALS AND METHODS: Inflammation-associated miRNA analysis was performed in 19 adults and 79 pediatric patients with ALL and involved miR-10, miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a, miR-222, miR-223, and miR-339...
November 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29050695/how-is-the-ph-like-signature-being-incorporated-into-all-therapy
#8
REVIEW
Luke Maese, Sarah K Tasian, Elizabeth A Raetz
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high risk disease subtype characterized by a gene expression profile similar to that observed in Philadelphia chromosome-positive (Ph-positive) ALL, but without an underlying BCR-ABL1 translocation. Adults and children with Ph-like ALL harbor a diversity of alterations that all lead to activated kinase signaling. Outcomes for patients with Ph-like ALL are poor, which has prompted investigation into the role of tyrosine kinase inhibitor (TKI)-based therapies for this disease...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050694/the-biology-of-philadelphia-chromosome-like-all
#9
REVIEW
Kathryn G Roberts
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poor survival in both children and adults...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050691/philadelphia-chromosome-negative-b-cell-acute-lymphoblastic-leukemia-in-older-adults-current-treatment-and-novel-therapies
#10
REVIEW
Kristen M O'Dwyer, Jane L Liesveld
Older adults with Philadelphia chromosome negative (Ph-),-B-cell acute lymphoblastic leukemia (ALL) have the highest rates of treatment failure and treatment complications with current therapy, and, thus, there is no standard treatment for these patients. Approximately 16 percent of patients with newly diagnosed Ph- B-cell ALL are aged 60 years or older [1]. The five-year overall survival for this older cohort of patients is approximately 20 percent, and there has been no improvement in their survival in decades [2]...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29047158/hyper-cvad-plus-nelarabine-in-newly-diagnosed-adult-t-cell-acute-lymphoblastic-leukemia-and-t-lymphoblastic-lymphoma
#11
Yasmin Abaza, Hagop M Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29043551/magi-1-expression-is-decreased-in-several-types-of-human-t-cell-leukemia-cell-lines-including-adult-t-cell-leukemia
#12
Takashi Kozakai, Masahiko Takahashi, Masaya Higuchi, Toshifumi Hara, Kousuke Saito, Yuetsu Tanaka, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Masahiro Fujii
Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1) is a cytoplasmic scaffold protein that interacts with various signaling molecules; it negatively controls the cell growth of various types of cells and positively controls cell-cell interaction. In T cells, MAGI-1 has been shown to inhibit Akt activity through its interaction with PTEN and MEK1. In this study we found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute lymphoblastic leukemia and chronic T-cell lymphocytic leukemia...
October 17, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29043149/pre-b-acute-lymphoblastic-leukemia-with-t-1-19-in-an-adult-initially-presenting-as-hematuria-and-bilateral-renal-enlargement-a%C3%A2-case-report-and-literature-review
#13
Jian Wu, Xiao-Ling Pi, Zhi-Bin Ye
Although pre-B acute lymphoblastic leukemia (ALL) is the most common type of renal leukemic infiltration; the renal infiltration with leukemia cells as the initial manifestation of leukemia is very rare. Translocation (1;19)(q23;p13) is one of the most common chromosomal abnormalities in patients with ALL and is observed in 5 - 6% of children with pre-B ALL. However, the incidence of t(1;19) in adults is lower, not exceeding 3%, and the prognosis of adult patients is usually poor. Herein, we report a 52-year-old female patient with pre-B ALL who initially presented as bilateral renal enlargement...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29031504/-therapeutic-targeting-of-notch-signaling-in-cancer
#14
REVIEW
Mehdi Brahmi, Olivia Bally, Lauriane Eberst, Philippe Cassier
The Notch pathway plays an essential role during embryonal development and tissue in adults. Notch signaling occurs through transmembrane receptors which undergo several proteolytic cleavages that lead to the release of the Notch intracytoplasmic domain (NICD), which in turn activates the transcription of target genes. Oncogenic alterations of Notch receptors were first identified in T acute lymphoblastic leukemia and subsequently in solid tumors and other hematological malignancies. The important role of Notch signaling in cancer makes it an interesting target for drug development...
October 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29029518/meta-analysis-of-the-clinical-characteristics-and-prognostic-relevance-of-notch1-and-fbxw7-mutation-in-t-cell-acute-lymphoblastic-leukemia
#15
Rong-Bin Liu, Jian-Gui Guo, Tian-Ze Liu, Cheng-Cheng Guo, Xin-Xiang Fan, Xiao Zhang, Wei-Han Hu, Xiu-Yu Cai
The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T-ALL). We performed a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) to assess the prognostic impact of mutations in the NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the Cochrane Library, we investigated overall survival (OS) and event-free survival (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and conducted subgroup analyses based on population and mutation status...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027638/fluconazole-versus-mould-active-triazoles-for-primary-antifungal-prophylaxis-in-adult-patients-with-acute-lymphoblastic-leukemia-clinical-outcome-and-cost-effectiveness-analysis
#16
Yan Wang, Yuanming Xing, Lu Chen, Ti Meng, Ying Li, Jiao Xie, Limei Chen, Yalin Dong, Weihua Dong
This study evaluated the clinical and cost-effectiveness of prophylactic use of fluconazole versus mould-active triazoles (voriconazole and posaconazole) in adult patients with acute lymphoblastic leukemia (ALL). A decision analytical model was developed with inputs from a 7-year retrospective study (2009-2016) of 103 consecutive adult patients with ALL who received antifungal prophylaxis. Information on the administration of antifungal agents, clinical outcomes, and costs were collected. One-way sensitivity analyses and probabilistic sensitivity analysis were performed...
October 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29025771/endothelial-activation-and-blood-brain-barrier-disruption-in-neurotoxicity-after-adoptive-immunotherapy-with-cd19-car-t-cells
#17
Juliane Gust, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, David Myerson, Luis F Gonzalez-Cuyar, Cecilia Yeung, W Conrad Liles, Mark Wurfel, Jose A Lopez, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Tahsin Özpolat, Kathleen R Fink, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19(+) cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability...
October 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29025601/a-neoplasm-with-fip1l1-pdgfra-fusion-presenting-as-pediatric-t-cell-lymphoblastic-leukemia-lymphoma-without-eosinophilia
#18
Matthew J Oberley, Christopher Denton, Jianling Ji, Matthew Hiemenz, Deepa Bhojwani, Dejerianne Ostrow, Samuel Wu, Paul Gaynon, Gordana Raca
The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025593/prognostic-significance-of-recurrent-additional-chromosomal-abnormalities-in-adult-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#19
Chang Ahn Seol, Young-Uk Cho, Seongsoo Jang, Chan-Jeoung Park, Jung-Hee Lee, Je-Hwan Lee, Kyoo Hyung Lee, Eul-Ju Seo
In Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), additional chromosomal abnormalities (ACAs) are frequently observed. We investigated the cytogenetic characteristics and prognostic significance of ACAs in Ph-positive ALL. We reviewed the clinical data and bone marrow cytogenetic findings of 122 adult Ph-positive ALL patients. The ACAs were examined for partial or whole chromosomal gains or losses, and structural aberrations. The overall survival (OS) and disease-free survival (DFS) of patients who received hematopoietic cell transplantation were compared between the isolated Ph group and ACA group...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025266/the-abcs-of-immunotherapy-for-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#20
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
October 1, 2017: Annals of Pharmacotherapy
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