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Acute Lymphoblastic leukemia in adults

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https://www.readbyqxmd.com/read/28340183/crlf2-positive-b-cell-acute-lymphoblastic-leukemia-in-adult-patients-a-single-institution-experience
#1
Sergej Konoplev, Xinyan Lu, Marina Konopleva, Nitin Jain, Juan Ouyang, Maitrayee Goswami, Kathryn G Roberts, Marc Valentine, Charles G Mullighan, Carlos Bueso-Ramos, Patrick A Zweidler-McKay, Jeffrey L Jorgensen, Sa A Wang
Objectives: Cytokine receptor-like factor 2 ( CRLF2 ) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2 + cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%)...
March 13, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28331334/safety-efficacy-and-clinical-utility-of-asparaginase-in-the-treatment-of-adult-patients-with-acute-lymphoblastic-leukemia
#2
REVIEW
Jamie Koprivnikar, James McCloskey, Stefan Faderl
Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28328172/acute-lymphoblastic-leukemia-in-adolescents-and-young-adults
#3
REVIEW
Michael E Rytting, Elias J Jabbour, Susan M O'Brien, Hagop M Kantarjian
Acute lymphoblastic leukemia (ALL) in the adolescent and young adult (AYA) population is a difficult clinical problem. The AYA population, generally regarded as patients aged 15 to 39 years, currently draws a good deal of attention, particularly in the area of therapy selection. The current trend is to treat this group of patients with leukemia regimens based on pediatric protocols, and results comparing pediatric approaches versus adult approaches to treatment are maturing. Results are pending from a large US trial in which pediatric-based treatment is given to AYA patients with ALL...
March 22, 2017: Cancer
https://www.readbyqxmd.com/read/28326824/osteopontin-its-potential-role-in-cancer-of-children-and-young-adults
#4
Gabrielle Karpinsky, Aleksandra Fatyga, Malgorzata Anna Krawczyk, Madeleine Chamera, Natalia Sande, Dagmara Szmyd, Ewa Izycka-Swieszewska, Ewa Bien
OBJECTIVE: Osteopontin (OPN) is aglyco-phosphoprotein, involved in tissue remodeling, inflammation and boneresorption. In various adult neoplasms OPN was shown to correlate with cancer progression, invasiveness and metastasis. AIM: to define the role of OPN in malignancies of children and young adults. MATERIAL AND METHODS: a structured PubMed and Google Scholar literature analysis based on reports published in English between I'1995 and XII'2015...
March 14, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28321121/dnmt3a-regulates-t-cell-development-and-suppresses-t-all-transformation
#5
A C Kramer, A Kothari, W C Wilson, H Celik, J Nikitas, C Mallaney, E L Ostrander, E Eultgen, A Martens, M C Valentine, A L Young, T E Druley, M E Figueroa, B Zhang, G A Challen
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises approximately 15 and 25% of pediatric and adult ALL cases respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28320465/reduced-microbial-diversity-in-adult-survivors-of-childhood-acute-lymphoblastic-leukemia-and-microbial-associations-with-increased-immune-activation
#6
Ling Ling Chua, Reena Rajasuriar, Mohamad Shafiq Azanan, Noor Kamila Abdullah, Mei San Tang, Soo Ching Lee, Yin Ling Woo, Yvonne Ai Lian Lim, Hany Ariffin, P'ng Loke
BACKGROUND: Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) have health problems that persist or develop years after cessation of therapy. These late effects include chronic inflammation-related comorbidities such as obesity and type 2 diabetes, but the underlying cause is poorly understood. RESULTS: We compared the anal microbiota composition of adult survivors of childhood ALL (N = 73) with healthy control subjects (N = 61)...
March 20, 2017: Microbiome
https://www.readbyqxmd.com/read/28318489/deletion-of-the-mad2l1-spindle-assembly-checkpoint-gene-is-tolerated-in-mouse-models-of-acute-t-cell-lymphoma-and-hepatocellular-carcinoma
#7
Floris Foijer, Lee A Albacker, Bjorn Bakker, Diana C Spierings, Ying Yue, Stephanie Z Xie, Stephanie H Davis, Annegret Lutum-Jehle, Darin Takemoto, Brian Hare, Brinley Furey, Roderick T Bronson, Peter M Lansdorp, Allan Bradley, Peter K Sorger
Chromosome instability (CIN) is deleterious to normal cells because of the burden of aneuploidy. However, most human solid tumors have an abnormal karyotype implying that gain and loss of chromosomes by cancer cells confers a selective advantage. CIN can be induced in the mouse by inactivating the spindle assembly checkpoint. This is lethal in the germline but we show here that adult T cells and hepatocytes can survive conditional inactivation of the Mad2l1 SAC gene and resulting CIN. This causes rapid onset of acute lymphoblastic leukemia (T-ALL) and progressive development of hepatocellular carcinoma (HCC), both lethal diseases...
March 20, 2017: ELife
https://www.readbyqxmd.com/read/28297628/genetic-basis-of-acute-lymphoblastic-leukemia
#8
Ilaria Iacobucci, Charles G Mullighan
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and despite cure rates exceeding 90% in children, it remains an important cause of morbidity and mortality in children and adults. The past decade has been marked by extraordinary advances into the genetic basis of leukemogenesis and treatment responsiveness in ALL. Both B-cell and T-cell ALL comprise multiple subtypes harboring distinct constellations of somatic structural DNA rearrangements and sequence mutations that commonly perturb lymphoid development, cytokine receptors, kinase and Ras signaling, tumor suppression, and chromatin modification...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295989/pharmacokinetics-of-two-6-mercaptopurine-liquid-formulations-in-children-with-acute-lymphoblastic-leukemia
#9
Jaszianne A Tolbert, Shasha Bai, Susan M Abdel-Rahman, Keith J August, Scott J Weir, Gregory L Kearns, Kathleen A Neville
BACKGROUND: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. METHODS: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28286617/allogeneic-hematopoietic-stem-cell-transplantation-for-adult-acute-lymphoblastic-leukemia-results-from-a-single-center-1993-2011
#10
Ipek Yonal-Hindilerden, Sevgi Kalayoglu-Besisik, Nuray Gurses-Koc, Fehmi Hindilerden, Deniz Sargin
Background: For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature. Subjects and Methods: This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28282510/cxcr4-cd184-expression-on-stem-cell-harvest-and-cd34-cells-post-transplant
#11
Inas Asfour, Hanaa Afify, Shaza Elkourashy, Maryse Ayoub, Gihan Kamal, Mary Gamal, Ghada Elgohary
OBJECTIVES/BACKGROUND: CXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism. METHODS: This is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014...
March 2, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#12
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28274393/low-dose-cranial-boost-in-high-risk-adult-acute-lymphoblastic-leukemia-patients-undergoing-bone-marrow-transplant
#13
William Su, Marcher Thompson, Ren-Dih Sheu, Amir Steinberg, Luis Isola, Richard Stock, Richard L Bakst
PURPOSE: Acute lymphoblastic leukemia (ALL) has a predilection for CNS involvement. Patients with high-risk ALL are often managed with transplant using a radiation-based conditioning regimen. Historically, a high-dose prophylactic cranial boost (CB) of ≥12 Gy was given to reduce risk of central nervous system (CNS) recurrence. However, the use of CB has fallen out of favor because of toxicity concerns. In high-risk adults undergoing transplant at our institution, we have used a low-dose 6 Gy CB to reduce toxicity while conditioning adults with fully developed brains...
March 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28270453/activation-of-the-lmo2-oncogene-through-a-somatically-acquired-neomorphic-promoter-in-t-cell-acute-lymphoblastic-leukemia
#14
Sunniyat Rahman, Michael Magnussen, Theresa E León, Nadine Farah, Zhaodong Li, Brian J Abraham, Krisztina Z Alapi, Rachel J Mitchell, Tom Naughton, Adele K Fielding, Arnold Pizzey, Sophia Bustraan, Christopher Allen, Teodora Popa, Karin Pike-Overzet, Laura Garcia-Perez, Rosemary E Gale, David C Linch, Frank J T Staal, Richard A Young, A Thomas Look, Marc R Mansour
Somatic mutations within non-coding genomic regions that aberrantly activate oncogenes have remained poorly characterized. Here we describe recurrent activating intronic mutations of LMO2, a prominent oncogene in T-cell acute lymphoblastic leukemia (T-ALL). Heterozygous mutations were identified in PF-382 and DU.528 T-ALL cell lines, in addition to 3.7% (6/160) of pediatric and 5.5% (9/163) of adult T-ALL patient samples. The majority of indels harbour putative de novo MYB, ETS1 or RUNX1 consensus binding sites...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28259746/acute-myeloid-leukemia-in-a-patient-with-thrombocytopenia-with-absent-radii-a-case-report-and-review-of-the-literature
#15
Maximilian Jameson-Lee, Katherine Chen, Ellen Ritchie, Tsiporah Shore, Omar Al-Khattab, Usama Gergis
Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia...
February 24, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28249141/blinatumomab-versus-chemotherapy-for-advanced-acute-lymphoblastic-leukemia
#16
RANDOMIZED CONTROLLED TRIAL
Hagop Kantarjian, Anthony Stein, Nicola Gökbuget, Adele K Fielding, Andre C Schuh, Josep-Maria Ribera, Andrew Wei, Hervé Dombret, Robin Foà, Renato Bassan, Önder Arslan, Miguel A Sanz, Julie Bergeron, Fatih Demirkan, Ewa Lech-Maranda, Alessandro Rambaldi, Xavier Thomas, Heinz-August Horst, Monika Brüggemann, Wolfram Klapper, Brent L Wood, Alex Fleishman, Dirk Nagorsen, Christopher Holland, Zachary Zimmerman, Max S Topp
Background Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. Methods In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy...
March 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28245840/prognostic-stratification-improvement-by-integrating-id1-id3-igj-gene-expression-signature-and-immunophenotypic-profile-in-adult-patients-with-b-all
#17
Nataly Cruz-Rodriguez, Alba L Combita, Leonardo J Enciso, Lauren F Raney, Paula L Pinzon, Olga C Lozano, Alba M Campos, Niyireth Peñaloza, Julio Solano, Maria V Herrera, Jovanny Zabaleta, Sandra Quijano
BACKGROUND: Survival of adults with B-Acute Lymphoblastic Leukemia requires accurate risk stratification of patients in order to provide the appropriate therapy. Contemporary techniques, using clinical and cytogenetic variables are incomplete for prognosis prediction. METHODS: To improve the classification of adult patients diagnosed with B-ALL into prognosis groups, two strategies were examined and combined: the expression of the ID1/ID3/IGJ gene signature by RT-PCR and the immunophenotypic profile of 19 markers proposed in the EuroFlow protocol by Flow Cytometry in bone marrow samples...
February 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28245371/-expression-of-cd146-in-adult-and-children-s-acute-b-cell-lymphoblastic-leukemia-and-its-significance
#18
Xiao-Qing Xie, Wei-Min Wang, Si-Lin Gan, Sheng-Mei Chen, Qiu-Tang Zhang, Xin-Sheng Xie, Yan-Fang Liu, Yuan-Dong Cheng, Yu-Feng Liu, Xue-Ju Xu, Hui Sun
OBJECTIVE: To explore the differences of CD146 expression in adult and children's acute B cell lymphoblastic leukemia(B-ALL), and its relation with clinical features, molecular biological and cytogenctic claracteristics. METHODS: The expression of CD146 in bone marrow samples from adult and children's B-ALL patients were detected by flow cytometry (FCM) and the relation of CD146 abnormal high expression with the patients' clinical features, molecular biological and cytogenetical characteristics, as well as other antigens were analyzed...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28244643/plasma-asparaginase-activity-asparagine-concentration-and-toxicity-after-administration-of-erwinia-asparaginase-in-children-and-young-adults-with-acute-lymphoblastic-leukemia-phase-i-ii-clinical-trial-in-japan
#19
Chitose Ogawa, Fumi Taguchi, Hiroaki Goto, Katsuyoshi Koh, Daisuke Tomizawa, Akira Ohara, Atsushi Manabe
BACKGROUND: A phase I/II study of Erwinia asparaginase in Japanese children and young adults with acute lymphoblastic leukemia (ALL) was performed to investigate its activity and toxicity. PROCEDURE: Eligible patients were in remission and had developed allergy to Escherichia coli asparaginase. Erwina asparaginase was intramuscularly administrated on days 2, 5, 7, 9, 11, and 13. To measure the plasma l-asparagine concentration (PAC), amino acids were derivatized with N(α) -(5-fluoro-2,4-dinitrophenyl)-l-leucinamide...
February 28, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28219219/-clinical-features-and-prognosis-in-cd10-pre-b-acute-lymphoblastic-leukemia
#20
X Y Gong, Y Wang, B C Liu, H Wei, C L Zhou, D Lin, K Q Liu, S N Wei, B F Gong, G J Zhang, Y T Liu, X L Zhao, Y Li, R X Gu, S W Qiu, Y C Mi, J X Wang
Objective: To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10(-)pre-B (CD10(-) pre B-ALL) . Methods: 6 adult cases with CD10(-) pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients' clinical features and prognosis. Results: CD10(-) pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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