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philadelphia chromosome-positive acute lymphoblastic leukemia

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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
#1
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...
April 18, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29650292/novel-compounds-that-target-lipoprotein-lipase-and-mediate-growth-arrest-in-acute-lymphoblastic-leukemia
#2
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/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
#3
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
#4
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
#5
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
#6
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
#7
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/29498925/dasatinib-in-pediatric-patients-with-chronic-myeloid-leukemia-in-chronic-phase-results-from-a-phase-ii-trial
#8
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...
March 2, 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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/29384978/efficacy-and-safety-of-autologous-peripheral-blood-stem-cell-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-a-study-protocol-for-a-multicenter-exploratory-prospective-study-auto-ph17-study
#13
MULTICENTER STUDY
Satoshi Nishiwaki, Isamu Sugiura, Yasuhiko Miyata, Shigeki Saito, Masashi Sawa, Tetsuya Nishida, Koichi Miyamura, Yachiyo Kuwatsuka, Akio Kohno, Masaaki Yuge, Masanobu Kasai, Hiroatsu Iida, Shingo Kurahashi, Masahide Osaki, Tatsunori Goto, Seitaro Terakura, Makoto Murata, Hiroyoshi Nishikawa, Hitoshi Kiyoi
INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29384412/severe-hypofibrinogenemia-associated-with-imatinib-and-prednisone-therapy-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#14
Mariarita Sciumè, Nicola Stefano Fracchiolla, Agostino Cortelezzi
No abstract text is available yet for this article.
January 31, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29358182/blinatumomab-for-minimal-residual-disease-in-adults-with-b-cell-precursor-acute-lymphoblastic-leukemia
#15
Nicola Gökbuget, Hervé Dombret, Massimiliano Bonifacio, Albrecht Reichle, Carlos Graux, Christoph Faul, Helmut Diedrich, Max S Topp, Monika Brüggemann, Heinz-August Horst, Violaine Havelange, Julia Stieglmaier, Hendrik Wessels, Vincent Haddad, Jonathan E Benjamin, Gerhard Zugmaier, Dirk Nagorsen, Ralf C Bargou
Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission after multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase-polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10-3 ) received blinatumomab 15 µg/m2 per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1...
April 5, 2018: Blood
https://www.readbyqxmd.com/read/29356285/response-to-ponatinib-before-hematopoietic-stem-cell-transplantation-in-a-child-with-relapsed-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#16
Masaki Yamamoto, Tsukasa Hori, Keita Igarashi, Hiroyuki Shimada, Hiroyuki Tsutsumi
No abstract text is available yet for this article.
January 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29318644/description-and-prognostic-significance-of-the-kinetics-of-minimal-residual-disease-status-in-adults-with-acute-lymphoblastic-leukemia-treated-with-hypercvad
#17
Ryan D Cassaday, Philip A Stevenson, Brent L Wood, Pamela S Becker, Paul C Hendrie, Brenda M Sandmaier, Jerald L Radich, Andrei R Shustov
HyperCVAD is a commonly-used regimen for adults with newly-diagnosed acute lymphoblastic leukemia (ALL). However, relatively little is known about the application of minimal residual disease (MRD) detection with this treatment. To address this, we studied 142 adults with ALL treated with hyperCVAD over a 10-year period who had MRD assessed by either multi-parameter flow cytometry or (for patients with Philadelphia chromosome positive ALL) reverse transcriptase polymerase chain reaction for the BCR-ABL1 translocation...
August 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29285010/variant-bcr-abl1-fusion-genes-in-adult-philadelphia-chromosome-positive-b-cell-acute-lymphoblastic-leukemia
#18
Stephen E Langabeer
No abstract text is available yet for this article.
2017: EXCLI Journal
https://www.readbyqxmd.com/read/29284366/pepsi%C3%A2-or-coke%C3%A2-influence-of-acid-on-dasatinib-absorption
#19
Randall W Knoebel, Richard A Larson
Dasatinib is a second generation ABL kinase inhibitor used in the management of chronic myeloid leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib's bioavailability is highly dependent on gastric pH. When proton-pump inhibitors (PPIs) are co-administered with dasatinib, absorption is significantly reduced. Cola intake at the time of drug administration has been demonstrated to lead to relevant increases in the bioavailability for other acid labile drugs during PPI treatment...
March 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29247779/allogeneic-stem-cell-transplantation-versus-tyrosine-kinase-inhibitors-combined-with-chemotherapy-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#20
Jing Wang, Qian Jiang, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Ya-Zhen Qin, Guo-Rui Ruan, Hao Jiang, Jin-Song Jia, Ting Zhao, Kai-Yan Liu, Bin Jiang, Xiao-Jun Huang
Here we compare outcomes between the tyrosine kinase inhibitors (TKIs) plus chemotherapy regimen and allogeneic hematopoietic stem cell transplantation (transplantation cohort) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and explore factors associated with prognosis. Data from 145 Ph+ ALL patients were analyzed retrospectively. Patients were treated with imatinib plus chemotherapy and then transplantation or continuous TKIs with chemotherapy based on patient preference...
December 13, 2017: Biology of Blood and Marrow Transplantation
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