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Philadelphia positive Acute lymphoblastic leukemia

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...
February 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
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
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
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
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
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
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)
Mariarita Sciumè, Nicola Stefano Fracchiolla, Agostino Cortelezzi
No abstract text is available yet for this article.
January 31, 2018: Leukemia & Lymphoma
Salwa S Saadeh, Mark R Litzow
Allogeneic hematopoietic stem cell transplant (allo-HSCT) has an important role in management of acute lymphoblastic leukemia (ALL). Proper patient selection is central to ensure optimal outcomes. Areas covered: This review covers various aspects of HSCT in ALL patients, including indications, donor selection, conditioning regimens, and post-transplant management. Expert commentary: Allo-HSCT is important in post-remission management of ALL but proper risk-stratification is a major challenge. Incorporation of minimal residual disease (MRD) and molecular testing will improve patient allocation...
January 29, 2018: Expert Review of Hematology
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/m2 /day by continuous intravenous infusion for up to four cycles...
January 22, 2018: Blood
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
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
ShenMiao Yang, Jing Wang, Ting Zhao, JinSong Jia, HongHu Zhu, Hao Jiang, Jin Lu, Bin Jiang, HongXia Shi, YanRong Liu, YueYun Lai, LanPing Xu, XiaoJun Huang, Qian Jiang
Patients with standard-risk adult acute lymphoblastic leukemia (ALL) treated with chemotherapy do not have satisfactory outcomes. To more precisely classify ALL patients and optimize treatment, we re-evaluated the risk stratification system by examining CD20 expression and other classic risk factors at diagnosis. We retrospectively analyzed response to induction chemotherapy of 217 consecutive patients with newly diagnosed Philadelphia-negative B cell precursor-ALL. Survival analyses were conducted for the 136 patients who were intended to be treated with chemotherapy alone...
December 1, 2017: Oncotarget
Stephen E Langabeer
No abstract text is available yet for this article.
2017: EXCLI Journal
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
Rachael F Grace, Daniel J DeAngelo, Kristen E Stevenson, Donna Neuberg, Stephen E Sallan, Yasser R Abou Mourad, Julie Bergeron, Matthew D Seftel, Caroline Kokulis, Jean M Connors
Treatment for acute lymphoblastic leukemia (ALL) in adults confers a high risk of venous thromboembolic (VTE) complications. We describe the implementation and results of prophylactic anticoagulation guidelines in adults (18-50 years) treated on a Dana-Farber Cancer Institute ALL pediatric inspired consortium protocol from 2007 to 2013. A high rate of asparaginase related toxicity events, including thrombosis, resulted in a protocol amendment adding guidelines for prophylactic anticoagulation and a modified asparaginase dose and schedule...
December 19, 2017: Journal of Thrombosis and Thrombolysis
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
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
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
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
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