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Relapsed acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28441264/cd19-isoforms-enabling-resistance-to-cart-19-immunotherapy-are-expressed-in-b-all-patients-at-initial-diagnosis
#1
Jeannette Fischer, Claudia Paret, Khalifa El Malki, Francesca Alt, Arthur Wingerter, Marie A Neu, Bettina Kron, Alexandra Russo, Nadine Lehmann, Lea Roth, Eva-M Fehr, Sebastian Attig, Alexander Hohberger, Thomas Kindler, Jörg Faber
B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy...
April 24, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28438676/factors-associated-with-long-term-risk-of-relapse-after-unrelated-cord-blood-transplantation-for-children-with-acute-lymphoblastic-leukemia-in-remission
#2
Kristin M Page, Myriam Labopin, Annalisa Ruggeri, Gerard Michel, Cristina Diaz de Heredia, Tracey O'Brien, Alessandra Picardi, Mouhab Ayas, Henrique Bittencourt, Ajay J Vora, Jesse Troy, Carmen Bonfim, Fernanda Volt, Eliane Gluckman, Peter Bader, Joanne Kurtzberg, Vanderson Rocha
For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared to other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GvHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence (CI) of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first (n=257, 40%) or second complete remission (CR; n=383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000-2012...
April 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28436979/successful-chimeric-ag-receptor-modified-t-cell-therapy-for-isolated-testicular-relapse-after-hematopoietic-cell-transplantation-in-an-acute-lymphoblastic-leukemia-patient
#3
J Yu, Y Hu, C Pu, Z Liang, Q Cui, H Zhang, Y Luo, J Shi, A Jin, L Xiao, Z Wu, H Huang
No abstract text is available yet for this article.
April 24, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28436581/pediatric-acute-lymphoblastic-leukemia-with-t-1-19-tcf3-pbx1-in-taiwan
#4
Hsiu-Ju Yen, Shih-Hsiang Chen, Tsung-Yen Chang, Chao-Ping Yang, Dong-Tsamn Lin, Iou-Jih Hung, Kai-Hsin Lin, Jiann-Shiuh Chen, Chih-Cheng Hsiao, Tai-Tsung Chang, Te-Kao Chang, Ching-Tien Peng, Ming-Tsan Lin, Tang-Her Jaing, Hsi-Che Liu, Shiann-Tarng Jou, Meng-Yao Lu, Chao-Neng Cheng, Jiunn-Ming Sheen, Shyh-Shin Chiou, Giun-Yi Hung, Kang-Hsi Wu, Ting-Chi Yeh, Shih-Chung Wang, Rong-Long Chen, Hsiu-Hao Chang, Yung-Li Yang, Shu-Huey Chen, Shin-Nan Cheng, Yu-Hsiang Chang, Bow-Wen Chen, Yuh-Lin Hsieh, Fang-Liang Huang, Wan-Ling Ho, Jinn-Li Wang, Chia-Yau Chang, Yu-Hua Chao, Pei-Chin Lin, Yu-Chieh Chen, Yu-Mei Liao, Tung-Huei Lin, Lee-Yung Shih, Der-Cherng Liang
BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28422613/the-impact-of-prospective-telemedicine-implementation-in-the-management-of-childhood-acute-lymphoblastic-leukemia-in-recife-brazil
#5
Francisco Pedrosa, Faisal Shaikh, Gaston Rivera, Raul Ribeiro, Ibrahim Qaddoumi
BACKGROUND: A gap in childhood cancer outcomes remains between developed and developing countries. Persistence of this gap may be caused by financial, social, or educational disparities. Twinning and distance learning initiatives may improve such disparities. Integrating telemedicine into pediatric oncology twinning programs enhances education and facilitates patient-centered capacity building. MATERIALS AND METHODS: We performed an analysis of Web-based meetings held from August 2005 through July 2009 between the International Outreach Program at St...
April 19, 2017: Telemedicine Journal and E-health: the Official Journal of the American Telemedicine Association
https://www.readbyqxmd.com/read/28419486/population-pharmacokinetic-analysis-of-bortezomib-in-pediatric-leukemia-patients-model-based-support-for-body-surface-area-based-dosing-over-the-2-to-16-year-age-range
#6
Michael J Hanley, Diane R Mould, Timothy J Taylor, Neeraj Gupta, Kaveri Suryanarayan, Rachel Neuwirth, Dixie-Lee Esseltine, Terzah M Horton, Richard Aplenc, Todd A Alonzo, Xiaomin Lu, Ashley Milton, Karthik Venkatakrishnan
This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1...
April 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28418909/pathogenesis-of-etv6-runx1-positive-childhood-acute-lymphoblastic-leukemia-and-mechanisms-underlying-its-relapse
#7
REVIEW
Congcong Sun, Lixian Chang, Xiaofan Zhu
ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed by a series of secondary mutations that trigger overt leukemia. The cellular framework in which E/R arises and the maintenance of a pre-leukemic condition by E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly, a variety of studies have focused on the relationship between the clones giving rise to the primary and recurrent E/R-positive ALL...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415593/cysteine-and-glycine-rich-protein-2-csrp2-transcript-levels-correlate-with-leukemia-relapse-and-leukemia-free-survival-in-adults-with-b-cell-acute-lymphoblastic-leukemia-and-normal-cytogenetics
#8
Shu-Juan Wang, Ping-Zhang Wang, Robert Peter Gale, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Hui Zhang, Bin Jiang, Lan-Ping Xu, Xiao-Jun Huang, Kai-Yan Liu, Guo-Rui Ruan
Relapse is the major cause of treatment-failure in adults with B-cell acute lymphoblastic leukemia (ALL) achieving complete remission after induction chemotherapy. Greater precision identifying persons likely to relapse is important. We did bio-informatics analyses of transcriptomic data to identify mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate genes for validation 7 of which proved significantly-associated with B-cell ALL. We next focused on function and clinical correlations of the cysteine and glycine-rich protein 2 (CSRP2)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413717/advances-of-cd19-directed-chimeric-antigen-receptor-modified-t-cells-in-refractory-relapsed-acute-lymphoblastic-leukemia
#9
REVIEW
Guoqing Wei, Lijuan Ding, Jiasheng Wang, Yongxian Hu, He Huang
Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28412288/adult-t-type-lymphoblastic-lymphoma-treatment-advances-and-prognostic-indicators
#10
REVIEW
Stéphane Lepretre, Carlos Graux, Aurore Touzart, Elizabeth Macintyre, Nicolas Boissel
T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor T cells that occurs mostly in adolescents and young adults. In this review, we describe the treatment of adult T-LBL with a focus on recent advances using pediatric-inspired acute lymphoblastic leukemia regimens, which have greatly improved outcome. We also discuss the development of prognostic indicators for T-LBL, especially oncogenetic factors, that can identify patients at higher risk of relapse and should help further extend T-LBL patient survival...
April 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#11
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28406385/retrospective-chart-review-of-hospitalizations-and-costs-associated-with-the-treatment-of-adults-with-philadelphia-negative-b-cell-relapsed-or-refractory-acute-lymphoblastic-leukemia-in-belgium
#12
Johan Maertens, Carlos Graux, Dimitri Breems, Violaine Havelange, Sebastian Wittnebel, Daniëlle Strens, Caroline Hoefkens
OBJECTIVES: To quantify hospitalizations and costs among adults with Philadelphia-negative relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) who received current salvage chemotherapies in Belgium. METHODS: A retrospective chart review identified patients aged ≥18 years and hospitalized between 2005 and 2015 for Ph-negative R/R B-cell ALL. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up...
April 13, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28396160/allogeneic-hematopoietic-cell-transplantation-hct-for-adult-t-cell-acute-lymphoblastic-leukemia-t-all
#13
Betty Ky Hamilton, Lisa Rybicki, Donna Abounader, Kehinde Adekola, Anjali Advani, Ibrahim Aldoss, Veronika Bachanova, Asad Bashey, Stacey Brown, Marcos DeLima, Steven Devine, Christopher R Flowers, Siddharth Ganguly, Madan Jagasia, Vanessa E Kennedy, Dennis Dong Hwan Kim, Joseph McGuirk, Vinod Pullarkat, Rizwan Romee, Karamjeet Sandhu, Melody Smith, Masumi Ueda, Auro Viswabandya, Khoan Vu, Sarah Wall, Simon B Zeichner, Miguel-Angel Perales, Navneet S Majhail
Allogeneic hematopoietic cell transplantation (HCT) is recommended for T-cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and in high risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multi-center retrospective cohort study using data from 208 adult patients transplanted from 2000-2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. Median age at HCT was 37 years and the majority of patients were transplanted in CR, using total body irradiation (TBI) based myeloablative conditioning regimens...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28395443/-clinical-analysis-of-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-p16-gene-deletion
#14
B L He, N Xu, Y L Li, C Y Pan, R Cao, L B Liao, C X Yin, Y Q Lan, Z Y Lu, J X Huang, H S Zhou, Q F Liu, X L Liu
Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph(+) ALL patients with p16 deletion. Results: Of 80 adult Ph(+) ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10(9)/L) and CD20 expression...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28394370/more-chronic-gvhd-and-non-relapse-mortality-after-peripheral-blood-stem-cell-compared-with-bone-marrow-in-hematopoietic-transplantation-for-paediatric-acute-lymphoblastic-leukemia-a-retrospective-study-on-behalf-of-the-ebmt-paediatric-diseases-working-party
#15
M Simonin, A Dalissier, M Labopin, A Willasch, M Zecca, A Mouhab, A Chybicka, A Balduzzi, L Volin, C Peters, P Bader, J-H Dalle
No abstract text is available yet for this article.
April 10, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28391009/the-promise-of-pharmacogenomics-in-reducing-toxicity-during-acute-lymphoblastic-leukemia-maintenance-treatment
#16
REVIEW
Shoshana Rudin, Marcus Marable, R Stephanie Huang
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity...
April 6, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28385156/childhood-pre-b-cell-acute-lymphoblastic-leukemia-with-translocation-t-1-19-q21-1-p13-3-and-two-additional-chromosomal-aberrations-involving-chromosomes-1-6-and-13-a-case-report
#17
Abdulsamad Wafa, Manar As'sad, Thomas Liehr, Abdulmunim Aljapawe, Walid Al Achkar
BACKGROUND: The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20...
April 7, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28371317/molecular-characterization-of-acute-lymphoblastic-leukemia-with-high-crlf2-gene-expression-in-childhood
#18
Juliane Schmäh, Birthe Fedders, Renate Panzer-Grümayer, Susanna Fischer, Martin Zimmermann, Elif Dagdan, Susanne Bens, Denis Schewe, Anja Moericke, Julia Alten, Kirsten Bleckmann, Reiner Siebert, Martin Schrappe, Martin Stanulla, Gunnar Cario
BACKGROUND: A high-level expression of the CRLF2 gene is frequent in precursor B-cell acute lymphoblastic leukemia (pB-ALL) and can be caused by different genetic aberrations. The presence of the most frequent alteration, the P2RY8/CRLF2 fusion, was shown to be associated with a high relapse incidence in children treated according to ALL-Berlin-Frankfurt-Münster (BFM) protocols, which is poorly understood. Moreover, the frequency of other alterations has not been systematically analyzed yet...
April 1, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28363872/novel-therapeutic-strategies-to-target-leukemic-cells-that-hijack-compartmentalized-continuous-hematopoietic-stem-cell-niches
#19
REVIEW
Vashendriya V V Hira, Cornelis J F Van Noorden, Hetty E Carraway, Jaroslaw P Maciejewski, Remco J Molenaar
Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28360149/notch1-mutation-tp53-alteration-and-myeloid-antigen-expression-predict-outcome-heterogeneity-in-children-with-first-relapse-of-t-cell-acute-lymphoblastic-leukemia
#20
Jana Hof, Corinne Kox, Stefanie Groeneveld-Krentz, Obul R Bandapalli, Leonid Karawajew, Katharina Schedel, Joachim B Kunz, Cornelia Eckert, Wolf-Dieter Ludwig, Richard Ratei, Peter Rhein, Günter Henze, Martina U Muckenthaler, Andreas E Kulozik, Arend von Stackelberg, Renate Kirschner-Schwabe
No abstract text is available yet for this article.
March 30, 2017: Haematologica
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