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Ph+ acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#1
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29768710/improving-the-safety-of-high-dose-methotrexate-for-children-with-hematologic-cancers-in-settings-without-access-to-mtx-levels-using-extended-hydration-and-additional-leucovorin
#2
Kalthi Vaishnavi, Deepak Bansal, Amita Trehan, Richa Jain, Savita Verma Attri
BACKGROUND: A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively...
May 16, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29768231/enhanced-stability-of-l-asparaginase-by-its-bioconjugation-to-poly-styrene-co-maleic-acid-and-ecoflex-nanoparticles
#3
Jaleh Varshosaz, Negin Anvari
Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L-asparaginase (L-ASNase) is one of the first drugs used in ALL treatment. Anti-tumor activity of L-ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L-ASNase polymer bioconjugate to improve pharmacokinetic, increase half-life and stability of the enzyme. The conjugations were achieved by the cross-linking agent of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29742077/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-adults-current-treatments-and-future-perspectives
#4
Musa Yilmaz, Hagop Kantarjian, Farhad Ravandi-Kashani, Nicholas J Short, Elias Jabbour
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs). With the successful incorporation of TKIs into chemotherapy regimens, remissions occur more frequently and patients live longer...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29739753/health-related-quality-of-life-in-adults-with-relapsed-refractory-acute-lymphoblastic-leukemia-treated-with-blinatumomab
#5
Max S Topp, Zachary Zimmerman, Paul Cannell, Hervé Dombret, Johan Maertens, Anthony Stein, Janet Franklin, Qui Tran, Ze Cong, Andre C Schuh
In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ≥1 post-baseline result were available in any EORTC multi-item scale or single-item measure...
May 8, 2018: Blood
https://www.readbyqxmd.com/read/29726059/two-novel-fusion-genes-aif1l-etv6-and-abl1-aif1l-result-together-with-etv6-abl1-from-a-single-chromosomal-rearrangement-in-acute-lymphoblastic-leukemia-with-prenatal-origin
#6
Julius Lukes, Eliska Potuckova, Lucie Sramkova, Jan Stary, Julia Starkova, Jan Trka, Felix Votava, Jan Zuna, Marketa Zaliova
Fusion genes resulting from chromosomal rearrangements represent a hallmark of childhood acute lymphoblastic leukemia (ALL). Unlike more common fusion genes generated via simple reciprocal chromosomal translocations, formation of the ETV6-ABL1 fusion gene requires 3 DNA breaks and usually results from an interchromosomal insertion. We report a child with ALL in which a single interchromosomal insertion led to the formation of ETV6-ABL1 and two novel fusion genes: AIF1L-ETV6 and ABL1-AIF1L. We demonstrate the prenatal origin of this complex chromosomal rearrangement, which apparently initiated the leukemogenic process, by successful backtracking of the ETV6-ABL1 fusion into the patient's archived neonatal blood...
May 4, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29694642/final-analysis-of-the-jalsg-ph-all202-study-tyrosine-kinase-inhibitor-combined-chemotherapy-for-ph-all
#7
Yoshihiro Hatta, Shuichi Mizuta, Keitaro Matsuo, Shigeki Ohtake, Masako Iwanaga, Isamu Sugiura, Noriko Doki, Heiwa Kanamori, Yasunori Ueda, Chikamasa Yoshida, Nobuaki Dobashi, Tomoya Maeda, Toshiaki Yujiri, Fumihiko Monma, Yoshikazu Ito, Fumihiko Hayakawa, Jin Takeuchi, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe
The Japan Adult Leukemia Study Group (JALSG) Ph+ALL202 study reported a high complete remission (CR) rate for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients treated with imatinib-combined chemotherapy. However, the long-term treatment efficacy remains uncertain. Here, we report a final analysis of the JALSG Ph+ALL202 study. The outcomes were compared with those of the JALSG ALL93 and ALL97 studies, which were conducted in the pre-imatinib era. Ninety-nine newly diagnosed Ph+ALL patients were enrolled in Ph+ALL202 (median age, 45 years; median follow-up, 4...
April 24, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29679774/comparable-results-of-autologous-and-allogeneic-haematopoietic-stem-cell-transplantation-for-adults-with-philadelphia-positive-acute-lymphoblastic-leukaemia-in-first-complete-molecular-remission-an-analysis-by-the-acute-leukemia-working-party-of-the-ebmt
#8
Sebastian Giebel, Myriam Labopin, Michael Potter, Xavier Poiré, Henrik Sengeloev, Gerard Socié, Anne Huynh, Boris V Afanasyev, Urs Schanz, Olle Ringden, Peter Kalhs, Dietrich W Beelen, Antonio M Campos, Tamás Masszi, Jonathan Canaani, Mohamad Mohty, Arnon Nagler
BACKGROUND: Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014...
June 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29665896/-a-modified-protocol-for-rapid-establishing-mouse-model-with-ph-positive-acute-lymphoblastic-leukemia
#9
Na Qi, Xue Wang, Qing-Yun Wu, Zhi-Ling Yan, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To investigate a modified protocol of establishing mouse Ph+ ALL model so as to provide a more convenient and more powerful tool for Ph+ ALL studies. METHODS: Immature B cells from BALB/c mice were transfected with the Mig190 retrovirus and infused into irradiated syngeneic mice. The immunophenotype was identified by flow cytometry, the BCR-ABL was identified by RT-PCR and Western blot. Leukemia cells isolated from sick mice were re-infused into syngeneic mice without irradiation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29625246/droplet-digital-pcr-is-a-robust-tool-for-monitoring-minimal-residual-disease-in-adult-philadelphia-positive-acute-lymphoblastic-leukemia
#10
Nicoletta Coccaro, Luisa Anelli, Antonella Zagaria, Paola Casieri, Giuseppina Tota, Paola Orsini, Luciana Impera, Angela Minervini, Crescenzio F Minervini, Cosimo Cumbo, Elisa Parciante, Paola Carluccio, Claudia Brunetti, Giorgina Specchia, Francesco Albano
The BCR-ABL1 p190 fusion transcript (m-bcr) is the most frequent variant observed in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). Qualitative-PCR and real-time quantitative PCR are the currently used methods to monitor minimal residual disease (MRD) in Ph+ ALL patients; for the latter, full standardization and an international quality validation are lacking. Here, we developed a droplet digital PCR (ddPCR) assay for MRD monitoring in p190+ ALL cases. The analytical performance was assessed by the limit of detection determination, demonstrating a reliability, sensitivity, and precision of the assay of up to 0...
April 3, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29603136/anti-thymocyte-globulin-improves-survival-free-from-relapse-and-graft-versus-host-disease-after-allogeneic-peripheral-blood-stem-cell-transplantation-in-patients-with-philadelphia-negative-acute-lymphoblastic-leukemia-an-analysis-by-the-acute-leukemia-working
#11
Tomasz Czerw, Myriam Labopin, Sebastian Giebel, Gérard Socié, Liisa Volin, Nathalie Fegueux, Tamás Masszi, Didier Blaise, Sridhar Chaganti, Jan J Cornelissen, Jakob Passweg, Johan Maertens, Maija Itälä-Remes, Depei Wu, Mohamad Mohty, Arnon Nagler
BACKGROUND: Mobilized peripheral blood stem cells are currently the predominant source of grafts for allogeneic transplantation (allogeneic peripheral blood stem cell transplantation [allo-PBSCT]), although, in comparison with bone marrow, their use is associated with an increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the incidence of cGVHD include the addition of anti-thymocyte globulin (ATG) to the pretransplant conditioning regimen. METHODS: The goal of this retrospective study was to analyze the effect of ATG on allo-PBSCT outcomes for adults with Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL)...
March 30, 2018: Cancer
https://www.readbyqxmd.com/read/29578162/the-autophagy-induced-by-curcumin-via-mek-erk-pathway-plays-an-early-anti-leukemia-role-in-human-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-sup-b15-cells
#12
Yong Guo, Qing Qing Shan, Ping Yu Gong, Sen Chun Wang
Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin has been shown to have inhibitory effects on cancers by inducing apoptosis and autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR, ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph+ ALL cells. Experiments here, were conducted to determine whether autophagy via MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph+ ALL...
2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29577208/hematopoietic-stem-cell-transplantation-for-adult-philadelphia-negative-acute-lymphoblastic-leukemia-in-the-first-complete-remission-in-the-era-of-minimal-residual-disease
#13
REVIEW
Christianne Bourlon, Dennis Lacayo-Leñero, Sergio I Inclán-Alarcón, Roberta Demichelis-Gómez
PURPOSE OF REVIEW: The purpose of this review is to discuss the potential role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia-negative (Ph- ) adult acute lymphoblastic leukemia (ALL) in first complete remission (CR1) in the era of minimal residual disease (MRD). RECENT FINDINGS: Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT...
March 26, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29575541/simultaneous-detection-of-abl1-mutation-and-ikzf1-deletion-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-using-a-customized-target-enrichment-system-panel
#14
M Aoe, H Ishida, T Matsubara, S Karakawa, H Kawaguchi, K Fujiwara, K Kanamitsu, K Washio, K Okada, M Shibakura, A Shimada
INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary...
March 25, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29574915/cyclophosphamide-versus-etoposide-in-combination-with-total-body-irradiation-as-conditioning-regimen-for-adult-patients-with-ph-negative-acute-lymphoblastic-leukemia-undergoing-allogeneic-stem-cell-transplant-on-behalf-of-the-alwp-of-the-ebmt
#15
Anna Czyz, Myriam Labopin, Sebastian Giebel, Gerard Socié, Jane Apperley, Liisa Volin, Péter Reményi, Ibrahim Yakoub-Agha, Kim Orchard, Mauricette Michallet, Gernot Stuhler, Sridhar Chaganti, Martin Murray, Mahmoud Aljurf, Adrian Bloor, Jacob Passweg, Jürgen Finke, Mohamad Mohty, Arnon Nagler
Allogeneic hematopoietic cell transplantation (alloHCT) with myeloablative conditioning based on total body irradiation (TBI) is widely used for the treatment of adults with acute lymphoblastic leukemia (ALL). TBI is most frequently administered in combination with either cyclophosphamide (Cy/TBI) or etoposide (Vp/TBI). The goal of this study was to retrospectively compare these two regimens. Adult patients with Ph-negative ALL treated with alloHCT in first or second complete remission who received Cy/TBI (n=1346) or Vp/TBI (n=152) conditioning were included in the analysis...
March 25, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29574396/comparison-of-intensive-pediatric-inspired-therapy-with-non-intensive-therapy-in-older-adults-aged-55-65-years-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia
#16
Josep-Maria Ribera, Olga García, Cristina Gil, Santiago Mercadal, Irene García-Cadenas, Pau Montesinos, Pere Barba, Susana Vives, José González-Campos, Mar Tormo, Jordi Esteve, Aurelio López, María José Moreno, Jordi Ribera, Natalia Alonso, Arancha Bermúdez, María Luz Amigo, Eulàlia Genescà, Daniel García, Ferran Vall-Llovera, Juan Miguel Bergua, Ramon Guàrdia, María Carmen Monteserín, Teresa Bernal, María Calbacho, María Pilar Martínez, Evarist Feliu
BACKGROUND AND OBJECTIVE: The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55-65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients. PATIENTS AND METHODS: The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07)...
May 2018: Leukemia Research
https://www.readbyqxmd.com/read/29572111/comparative-analysis-of-flow-cytometry-and-rq-pcr-for-the-detection-of-minimal-residual-disease-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-after-hematopoietic-stem-cell-transplantation
#17
Xiangyu Zhao, Xiaosu Zhao, Huan Chen, Yazhen Qin, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Xiaojun Huang, Yingjun Chang
The aim of this study was to examine the value of MRD detection by multiparameter flow cytometry (MFC) and RQ-PCR at the early stage after hematopoietic stem cell transplantation (HSCT) for predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome-positive ALL (Ph+-ALL). Patients who maintained complete molecular remission (CMR, BCR/ABL<0.01%) status at 1 and 3 months were associated with a lower relapse rate (P=0.02 and <0.001) and better LFS (P=0.014 and 0.013) than those without a CMR...
March 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29562467/-prognostic-factors-of-pediatric-patients-with-ph-positive-acute-lymphoblastic-leukemia
#18
Y J Xue, J Wu, Y X Zuo, Y P Jia, A D Lu, L P Zhang
Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29562444/-efficacy-comparison-of-sequential-treatment-with-first-line-administration-of-second-generation-and-first-generation-tyrosine-kinase-inhibitors-in-patients-with-ph-acute-lymphoblastic-leukemia-followed-by-allogeneic-hematopoietic-stem-cell-transplantation
#19
F Yang, W Z Cai, X D Yang, S N Chen, X W Tang, A N Sun, D P Wu, W Q Qian, H Y Qiu
Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph+ ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29562441/-spectrum-of-somatic-mutations-and-their-prognostic-significance-in-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#20
J Feng, X Y Gong, Y J Jia, K Q Liu, Y Li, X B Dong, Q Y Fang, K Ru, Q H Li, H J Wang, X L Zhao, Y N Jia, Y Song, Z Tian, M Wang, K J Tang, J X Wang, Y C Mi
Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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