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Philadelphia positive Acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#1
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29742077/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-adults-current-treatments-and-future-perspectives
#2
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/29733512/survival-analysis-of-adult-patients-with-all-in-mexico-city-first-report-from-the-acute-leukemia-workgroup-alwg-gtla
#3
Erick Crespo-Solis, Karla Espinosa-Bautista, Martha Alvarado-Ibarra, Etta Rozen-Fuller, Fernando Pérez-Rocha, Chantal Nava-Gómez, Maricela Ortiz-Zepeda, José Luis Álvarez-Vera, Christian Omar Ramos-Peñafiel, Luis Antonio Meillón-García, Sergio Rodríguez-Rodríguez, Alan Pomerantz-Okon, Francisco Javier Turrubiates-Hernández, Roberta Demichelis-Gómez
Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29713210/inotuzumab-ozogamicin-in-the-treatment-of-relapsed-refractory-acute-b-cell-lymphoblastic-leukemia
#4
REVIEW
Natalie Uy, Michelle Nadeau, Maximilian Stahl, Amer M Zeidan
The improvement in outcomes of adult patients with acute lymphoblastic leukemia (ALL) has been modest, with the exception of Philadelphia chromosome-positive disease, despite advances in supportive care and stem cell transplantation. The recent approvals of novel agents, including the bispecific T-cell engager blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin, and chimeric antigen receptor T-cell products are changing the management of B-ALL, which traditionally relied on chemotherapy-based approaches...
2018: Journal of Blood Medicine
https://www.readbyqxmd.com/read/29694642/final-analysis-of-the-jalsg-ph-all202-study-tyrosine-kinase-inhibitor-combined-chemotherapy-for-ph-all
#5
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
#6
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/29662872/a-rare-variant-of-t-17-19-in-a-case-of-philadelphia-positive-adult-acute-lymphoblastic-leukemia-presenting-with-disseminated-intravascular-coagulation
#7
Moeinadin Safavi, Akbar Safaei, Mahnaz Lotfi
No abstract text is available yet for this article.
March 2018: Blood Research
https://www.readbyqxmd.com/read/29650292/novel-compounds-that-target-lipoprotein-lipase-and-mediate-growth-arrest-in-acute-lymphoblastic-leukemia
#8
Rajesh R Nair, Werner J Geldenhuys, Debbie Piktel, Prabodh Sadana, Laura F Gibson
Over the past decade, the therapeutic strategies employed to treat B-precursor acute lymphoblastic leukemia (ALL) have been progressively successful in treating the disease. Unfortunately, the treatment associated dyslipidemia, either acute or chronic, is very prevalent and a cause for decreased quality of life in the surviving patients. To overcome this hurdle, we tested a series of cylopropanecarboxamides, a family demonstrated to target lipid metabolism, for their anti-leukemic activity in ALL. Several of the compounds tested showed anti-proliferative activity, with one, compound 22, inhibiting both Philadelphia chromosome negative REH and Philadelphia chromosome positive SupB15 ALL cell division...
March 23, 2018: Bioorganic & Medicinal Chemistry Letters
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
#9
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/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
#10
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/29575541/simultaneous-detection-of-abl1-mutation-and-ikzf1-deletion-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-using-a-customized-target-enrichment-system-panel
#11
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/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
#12
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/29567798/ponatinib-efficacy-and-safety-in-philadelphia-chromosome-positive-leukemia-final-5-year-results-of-the-phase-2-pace-trial
#13
Jorge E Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D le Coutre, Ronald Paquette, Charles Chuah, Franck E Nicolini, Jane F Apperley, H Jean Khoury, Moshe Talpaz, Daniel J DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C Müller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Victor M Rivera, Frank G Haluska, François Guilhot, Michael W Deininger, Andreas Hochhaus, Timothy P Hughes, Neil P Shah, Hagop M Kantarjian
Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I The pivotal phase 2 PACE trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia resistant/intolerant to dasatinib or nilotinib, or with BCR ABL1T315I This analysis focuses on chronic-phase CML (CP-CML) patients (n=270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and MR4...
March 22, 2018: Blood
https://www.readbyqxmd.com/read/29552179/prognostic-significance-of-copy-number-alterations-detected-by-multi-link-probe-amplification-of-multiple-genes-in-adult-acute-lymphoblastic-leukemia
#14
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
https://www.readbyqxmd.com/read/29519619/efficacy-of-ponatinib-versus-earlier-generation-tyrosine-kinase-inhibitors-for-front-line-treatment-of-newly-diagnosed-philadelphia-positive-acute-lymphoblastic-leukemia
#15
Elias Jabbour, Maral DerSarkissian, Mei Sheng Duh, Nora McCormick, Wendy Y Cheng, Lisa J McGarry, Ariadne Souroutzidis, Hui Huang, Susan O'Brien, Farhad Ravandi, Hagop M Kantarjian
INTRODUCTION: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). PATIENTS AND METHODS: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29498925/dasatinib-in-pediatric-patients-with-chronic-myeloid-leukemia-in-chronic-phase-results-from-a-phase-ii-trial
#16
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...
May 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29464092/mtor-inhibition-enhances-efficacy-of-dasatinib-in-abl-rearranged-ph-like-b-all
#17
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
https://www.readbyqxmd.com/read/29434963/a-rare-e14a3-bcr-abl-fusion-transcript-in-acute-lymphoblastic-leukemia-patient-treated-with-car-modified-t-cell-therapy
#18
Haodong Cai, Li Yang, Kefeng Shen, Wei Zhang, Jie Xiong, Meilan Zhang, Xia Mao, Ying Wang, Min Xiao
E14a3 breakpoint cluster region (BCR)/ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL) fusion transcript is rare in Philadelphia chromosome positive disease, particularly in acute lymphoblastic leukemia (ALL). Recently an e14a3 fusion transcript was detected by multiple laboratory examinations, and the patient was suffering from ALL. Except for the BCR/ABL fusion gene, in the present study the patient additionally had an IKAROS family zinc finger 1 deletion which, has been confirmed as a significant adverse prognosis factor...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29429020/leukemia-propagating-cells-demonstrate-distinctive-gene-expression-profiles-compared-with-other-cell-fractions-from-patients-with-de-novo-philadelphia-chromosome-positive-all
#19
COMPARATIVE STUDY
Hong-Yan Zhao, Yang Song, Xie-Na Cao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Yuan Kong
Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph+ ALL. Using a xenograft assay, LPCs enrichment in the CD34+ CD38- CD58- fraction in Ph+ ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph+ ALL. However, little is known about the potential molecular mechanism of LPCs-mediated relapse...
May 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29388066/infections-in-patients-on-bcr-abl-tyrosine-kinase-inhibitor-therapy-cases-and-review-of-the-literature
#20
Bettina M Knoll, K Seiter
The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data...
January 31, 2018: Infection
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