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Acute lymphoblastic leukemia and philadelphia chromosome positive

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https://www.readbyqxmd.com/read/28419558/age-but-not-philadelphia-positivity-impairs-outcome-in-older-elderly-patients-with-acute-lymphoblastic-leukemia-in-sweden
#1
Piotr Kozlowski, Emma Lennmyr, Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Holger Karbach, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åström, Heléne Hallböök
OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype...
April 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28401025/adult-acute-precursor-b-cell-lymphoblastic-leukemia-presenting-as-hypercalcemia-and-osteolytic-bone-lesions
#2
Nikki Charlotta Paul Granacher, Zwi N Berneman, Wilfried Schroyens, Ann L R Van de Velde, Anke Verlinden, Alain P A Gadisseur
BACKGROUND: Osteolytic bone lesions and hypercalcemia without peripheral blasts B-cell acute lymphoblastic leukemia (B-ALL) is reported in children but rarely seen in adults. CASE PRESENTATION: We describe the case of a 34-year old man presenting with hypercalcemia and symptomatic osteolytic bone lesions of vertebrae and ribs who was initially suspected as having a solid malignancy. Diagnostic work-up including peripheral blood examination, radiographic and nuclear studies could, however, not detect a primary tumor...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28395443/-clinical-analysis-of-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-p16-gene-deletion
#3
B L He, N Xu, Y L Li, C Y Pan, R Cao, L B Liao, C X Yin, Y Q Lan, Z Y Lu, J X Huang, H S Zhou, Q F Liu, X L Liu
Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph(+) ALL patients with p16 deletion. Results: Of 80 adult Ph(+) ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10(9)/L) and CD20 expression...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28390196/pi3k-isoform-inhibition-associated-with-anti-bcr-abl-drugs-shows-in-vitro-increased-anti-leukemic-activity-in-philadelphia-chromosome-positive-b-acute-lymphoblastic-leukemia-cell-lines
#4
Simona Ultimo, Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Camilla Evangelisti, Claudio Celeghini, James A McCubrey, Giorgia Marisi, Paola Ulivi, Silvano Capitani, Luca M Neri
B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387926/overall-survival-with-ponatinib-versus-allogeneic-stem-cell-transplantation-in-philadelphia-chromosome-positive-leukemias-with-the-t315i-mutation
#5
Franck E Nicolini, Grzegorz W Basak, Dong-Wook Kim, Eduardo Olavarria, Javier Pinilla-Ibarz, Jane F Apperley, Timothy Hughes, Dietger Niederwieser, Michael J Mauro, Charles Chuah, Andreas Hochhaus, Giovanni Martinelli, Maral DerSarkissian, Mei Sheng Duh, Lisa J McGarry, Hagop M Kantarjian, Jorge E Cortes
BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted...
April 7, 2017: Cancer
https://www.readbyqxmd.com/read/28355115/complete-hematologic-and-molecular-response-in-adult-patients-with-relapsed-refractory-philadelphia-chromosome-positive-b-precursor-acute-lymphoblastic-leukemia-following-treatment-with-blinatumomab-results-from-a-phase-ii-single-arm-multicenter-study
#6
Giovanni Martinelli, Nicolas Boissel, Patrice Chevallier, Oliver Ottmann, Nicola Gökbuget, Max S Topp, Adele K Fielding, Alessandro Rambaldi, Ellen K Ritchie, Cristina Papayannidis, Lulu Ren Sterling, Jonathan Benjamin, Anthony Stein
Purpose Few therapeutic options are available for patients with Philadelphia chromosome-positive (Ph(+)) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph(+) ALL. Patients and Methods This open-label phase II study enrolled adults with Ph(+) ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib...
March 29, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28349299/efficacy-and-prognostic-factors-of-imatinib-plus-callg2008-protocol-in-adult-patients-with-newly-diagnosed-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#7
Yinjun Lou, Yafang Ma, Chenyin Li, Sansan Suo, Hongyan Tong, Wenbin Qian, Wenyuan Mai, Haitao Meng, Wenjuan Yu, Liping Mao, Juyin Wei, Weilei Xu, Jie Jin
A CALLG2008 protocol was developed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult acute lymphoblastic leukemia (ALL). We retrospectively analyzed 153 newly diagnosed adult patients with Philadelphia chromosome (Ph)-positive ALL enrolled into imatinib (400 mg/d) plus CALLG2008 regimen between 2009 and 2015. The median age was 40 years (range, 18-68 years), with 81 (52.3%) males. The overall hematologic complete remission (CR) rate was 96.7% after induction. With a median follow-up of 24...
March 27, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28326207/dasatinib-and-prednisolone-induction-therapy-for-a-case-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-dilated-cardiomyopathy-accompanied-by-life-threatening-ventricular-tachycardia
#8
Mitsutaka Nishimoto, Hirohisa Nakamae, Kana Matsumoto, Kunihiko Morita, Yuki Koga, Dai Momose, Masayuki Hino
A 56-year-old man being treated for dilated cardiomyopathy presented with epigastralgia. He was diagnosed with ventricular tachycardia and Philadelphia chromosome-positive acute lymphoblastic leukemia. After treating incessant ventricular tachycardia, we commenced induction therapy for leukemia with dasatinib and prednisolone to minimize toxicity towards cardiomyocytes and the cardiac conduction system. Although dasatinib was temporarily withheld because of a recurrence of ventricular tachycardia, we rechallenged dasatinib while using bisoprolol and amiodarone and achieved a complete hematological response three weeks later...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28270354/isolated-skin-relapse-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-after-allogeneic-stem-cell-transplant
#9
Masumi Ueda, Carlos Silva, Linda Baer, Paolo F Caimi, Kevin Cooper, Kord Honda, Marcos de Lima
No abstract text is available yet for this article.
January 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28243848/new-treatment-strategies-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#10
REVIEW
Lalit Saini, Joseph Brandwein
PURPOSE OF REVIEW: To review recent studies that address important questions regarding the treatment of Philadelphia chromosome-positive ALL. RECENT FINDINGS: Less intensive non-myelosuppressive induction approaches can produce comparable anti-leukemic responses with less toxicity. Second-generation tyrosine kinase inhibitors (TKIs) are not clearly associated with superior outcomes compared to imatinib. Ponatinib is associated with lower early relapse rates, but has additional vascular risks...
February 27, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28186983/differentiation-status-of-primary-chronic-myeloid-leukemia-cells-affects-sensitivity-to-bcr-abl1-inhibitors
#11
Paavo O Pietarinen, Christopher A Eide, Pilar Ayuda-Durán, Swapnil Potdar, Heikki Kuusanmäki, Emma I Andersson, John P Mpindi, Tea Pemovska, Mika Kontro, Caroline A Heckman, Olli Kallioniemi, Krister Wennerberg, Henrik Hjorth-Hansen, Brian J Druker, Jorrit M Enserink, Jeffrey W Tyner, Satu Mustjoki, Kimmo Porkka
Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12)...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184964/absorption-metabolism-and-excretion-of-14-c-ponatinib-after-a-single-oral-dose-in-humans
#12
Yihua E Ye, Caroline N Woodward, Narayana I Narasimhan
PURPOSE: Ponatinib is a novel tyrosine kinase inhibitor (TKI) specifically designed to inhibit native and mutated BCR-ABL. In the United States, ponatinib has received accelerated approval for adults with T315I-positive chronic myeloid leukemia (CML) or T315I (gatekeeper mutation)-positive, Philadelphia chromosome-positive, acute lymphoblastic leukemia (Ph + ALL), and patients with CML or Ph + ALL for whom no other TKI therapy is indicated. The objective of this phase 1, mass balance study was to evaluate the absorption, metabolism, and excretion of [(14)C]ponatinib in healthy subjects...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28103625/phase-ii-study-of-imatinib-based-chemotherapy-for-newly-diagnosed-bcr-abl-positive-acute-lymphoblastic-leukemia
#13
Shin Fujisawa, Shuichi Mizuta, Hideki Akiyama, Yasunori Ueda, Yasutaka Aoyama, Yoshihiro Hatta, Kazuhiko Kakihana, Nobuaki Dobashi, Isamu Sugiura, Yasushi Onishi, Tomoya Maeda, Kiyotoshi Imai, Shigeki Ohtake, Yasushi Miyazaki, Kazunori Ohnishi, Keitaro Matsuo, Tomoki Naoe
This study investigated the efficacy of imatinib based therapy with intensified consolidation therapy in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to prevent early relapse. We conducted a phase II trial of imatinib-combined chemotherapy for newly diagnosed BCR-ABL-positive ALL in adults. Sixty-eight patients were included in the trial between October 2008 and December 2010. The median age was 49 years, with 28 patients >55 years of age. Sixty-five patients achieved CR (95...
April 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28032081/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-8-years-experience-from-a-tertiary-care-center-in-india
#14
Madhav Danthala, Sadashivudu Gundeti, Laxmi Srinivas Maddali, Ashok Pillai, Krishna Chaitanya Puligundla, Raja Praveen Adusumilli
INTRODUCTION: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL...
October 2016: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28024472/-effect-of-brd4-inhibitor-gsk525762a-on-proliferation-and-apoptosis-of-sup-b15-cells-in-vitro-and-its-possible-mechanism
#15
Xue Wang, Na Qi, Sha Ma, Zhi-Ling Yan, Qing-Yun Wu, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To investigate the effect of BRD4 inhibitor GSK525762A on the proliferation and apoptosis of Philadelphia chromosome-positive acute lymphoblastic leukemia SUP-B15 cells and its mechanism. METHODS: SUP-B15 cells were treated with different concentration of GSK525762A, the proliferation-inhibition curve was assayed and plotted by CCK-8 method, the cell viability and apoptosis were detected by flow cytometry with Annexin V and 7-AAD staining. The transcripts of anti-apoptotic genes C-MYC, CDK6 and BCL-2 were detected by real-time PCR...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#16
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/28002337/anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-two-case-reports
#17
Yang-Min Zhu, Zhao Wu, You-Ping Tan, Yuan-Yuan Du, Zhi Liu, Rui-Ming Ou, Shuang Liu, Cheng-Fei Pu, Jing Jiang, Jin-Ping Wang, Lei Xiao, Qing Zhang
RATIONALE: The presence of the Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (ALL) has been associated with a high risk of disease relapse and a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for adults with Ph-positive ALL, but relapse remains the primary cause of treatment failure, and is associated with an extremely poor prognosis. The emergence of resistance to tyrosine kinase inhibitors (TKIs) poses a challenge for patients with disease relapses after initial treatment with TKI-containing regimens...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27988194/hyper-cvad-compared-with-bfm-like-chemotherapy-for-the-treatment-of-adult-acute-lymphoblastic-leukemia-a-retrospective-single-center-analysis
#18
Jean El-Cheikh, Imane El Dika, Radwan Massoud, Maya Charafeddine, Rami Mahfouz, Mohamed A Kharfan-Dabaja, Ali Bazarbachi
BACKGROUND: Several induction regimens have been developed for treatment of adult patients with acute lymphoblastic leukemia (ALL). However, only a few prospective randomized trials have directly compared these regimens. PATIENTS AND METHODS: In this report, we retrospectively evaluated the outcome of 62 adult ALL patients treated with either hyper-CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; n = 38) or a BFM (Berlin-Frankfurt-Munster)-like regimen (n = 24) between November 2000 and January 2016 at the American university of Beirut Medical Center in Lebanon...
March 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27987201/treatment-of-acute-lymphoblastic-leukemia-in-adults-applying-lessons-learned-in-children
#19
REVIEW
Ibrahim T Aldoss, Guido Marcucci, Vinod Pullarkat
Although pediatric acute lymphoblastic leukemia (ALL) has cure rates of over 90%, adult ALL remains a challenging disease to treat, with cure rates roughly half those seen in children. The inferior outcomes in adults can be attributed mainly to adverse genetic features, as well as the inability-particularly of older adults-to tolerate chemotherapy. Modest improvements have been seen in outcomes for adolescents and young adults; these can largely be attributed to the use of pediatric-type combination chemotherapy regimens in patients aged 50 years or younger...
December 15, 2016: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/27930641/should-treatment-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-be-intensive-intensive-treatment-is-not-necessary-at-least-in-induction
#20
REVIEW
Sabina Chiaretti
No abstract text is available yet for this article.
November 2016: Clinical Advances in Hematology & Oncology: H&O
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