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philadelphia chromosome-positive acute lymphoblastic leukemia

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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
#1
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
#2
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...
February 10, 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
#3
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
#4
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
#5
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-precursor-acute-lymphoblastic-leukemia
#6
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 30-50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission following 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/m 2 /day by continuous intravenous infusion for up to four cycles...
January 22, 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
#7
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
#8
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...
January 10, 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
#9
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
#10
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...
January 1, 2017: 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
#11
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
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#12
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29233926/targeting-cdk6-and-bcl2-exploits-the-myb-addiction-of-ph-acute-lymphoblastic-leukemia
#13
Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A Mariani, Sankar Addya, Paolo Fortina, Luke F Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1-dependent and -independent mechanisms. Newly developed TKI can target Ph+ ALL cells with BCR-ABL1-dependent resistance; however, overcoming BCR-ABL1-independent mechanisms of resistance remains challenging because transcription factors (TF), which are difficult to inhibit, are often involved...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29222233/current-management-of-philadelphia-chromosome-positive-all-and-the-role-of-stem-cell-transplantation
#14
REVIEW
Farhad Ravandi
Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29214878/combination-of-ikzf1-deletion-and-early-molecular-response-show-significant-roles-on-prognostic-stratification-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patients
#15
He Li, Wanhua Zhang, Pu Kuang, Yuanxin Ye, Jinjun Yang, Yang Dai, Xiaojun Lu, Yuhuan Zheng, Ting Liu
We retrospectively analyzed the samples collected from 66 patients with Ph+ALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.7 ± 11.7% and 26.9 ± 11.6%, 3-year OS and DFS were 31.6 ± 12.0% and 23.4 ± 11.6%. By combining IKZF1 deletion and early molecular responses, we redefined the patients as low, intermediate, and high risk 3 groups separately. Patients with double negative in IKZF1 and early molecular response experienced significant superior survival, while patients with double positive would have the worst outcome, and patients who were one or the other with IKZF1 deletion or MRD status had intermediate outcome...
December 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29212977/-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-complicated-by-concomitant-achromobacter-xylosoxidans-and-corynebacterium-striatum-bacteremia-following-allogeneic-hematopoietic-stem-cell-transplantation
#16
Yuta Katayama, Kouhei Kyo, Koji Iwato, Takeshi Okatani, Ryota Imanaka, Mitsuhiro Itagaki, Shinya Katsutani, Hideki Asaoku
A 54-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) underwent hematopoietic stem cell transplantation from an HLA-matched sibling. Subsequently, she suffered from chronic graft versus host disease (GvHD) and received medical treatment. Fever developed on day 697 and resulted in a shock state at 10 h after the visit. Achromobacter xylosoxidans was detected in the initial blood culture on day 699. General conditions exacerbated even after the start of meropenem hydrate (MEPM, Meropen®) administration, with Corynebacterium striatum detected as an additional species in the initial blood culture on day 701...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29212964/simple-determination-of-plasma-ponatinib-concentration-using-hplc
#17
Takeo Yasu, Kenji Momo, Shunsuke Kobayashi, Seiichirou Kuroda, Arinobu Tojo
Ponatinib, a novel tyrosine kinase inhibitor marketed in 2016, is a key drug used for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. This study aimed to develop a simple method for determining plasma ponatinib concentration. The analysis required extraction of a 400-μL sample of plasma and precipitation of proteins using an Oasis HLB cartridge. Ponatinib and bosutinib, which is used as an internal standard, were separated by HPLC using a mobile phase of acetonitrile: 0...
December 6, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29188580/10-year-complete-remission-in-a-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patient-using-imatinib-without-high-intensity-chemotherapy-or-allogeneic-stem-cell-transplantation
#18
Katsumichi Fujimaki, Yukako Hattori, Hideaki Nakajima
The outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has improved with the use of tyrosine kinase inhibitors, such as imatinib and dasatinib. We report a 63-year-old woman with Ph-ALL who maintained complete remission for 10 years using imatinib without high-intensity chemotherapy or allogeneic stem cell transplantation. She underwent induction therapy with imatinib plus prednisolone and achieved complete remission by day 53. Imatinib was continued until 103 months, when it was stopped in response to renal dysfunction; however, the patient continued to exhibit molecular remission at 120 months...
November 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29152059/gzd824-suppresses-the-growth-of-human-b-cell-precursor-acute-lymphoblastic-leukemia-cells-by-inhibiting-the-src-kinase-and-pi3k-akt-pathways
#19
Wei Ye, Zhiwu Jiang, Xiaoyun Lu, Xiaomei Ren, Manman Deng, Shouheng Lin, Yiren Xiao, Simiao Lin, Suna Wang, Baiheng Li, Yi Zheng, Peilong Lai, Jianyu Weng, Donghai Wu, Yuguo Ma, Xudong Chen, Zhesheng Wen, Yaoyu Chen, Xiaoyan Feng, Yangqiu Li, Pentao Liu, Xin Du, Duanqing Pei, Yao Yao, Bing Xu, Ke Ding, Peng Li
Available therapeutic options for advanced B cell precursor acute lymphoblastic leukemia (pre-B ALL) are limited. Many lead to neutropenia, leaving patients at risk of life-threatening infections and result in bad outcomes. New treatment options are needed to improve overall survival. We previously showed that GZD824, a novel BCR-ABL tyrosine kinase inhibitor, has anti-tumor activity in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia cells and tumor models. Here, we show that GZD824 decreases cell viability, induces cell-cycle arrest, and causes apoptosis in pre-B ALL cells...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29140408/philadelphia-chromosome-like-mixed-phenotype-acute-leukemia-demonstrating-p2ry8-crlf2-fusion-and-jak1-mutation
#20
Sarah M Choi, John K Frederiksen, Charles W Ross, Dale L Bixby, Lina Shao
Objectives: Philadelphia chromosome-like (Ph-like) genetic alterations define a subset of B lymphoblastic leukemia/lymphoma (B-ALL), which represents a separate provisional entity in the World Health Organization 2016 updated classification. However, these alterations have not been described outside the context of B-ALL. Methods: Cytogenomic array and molecular analysis identified a Ph-like signature in a mixed-phenotype acute leukemia (MPAL), B/myeloid, confirmed using conventional immunophenotypic and cytochemical analysis...
November 20, 2017: American Journal of Clinical Pathology
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