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Ph+ acute lymphoblastic leukemia

Sapan J Patel, Costel C Darie, Bayard D Clarkson
Tumors contain heterogeneous cell populations and achieve dominance by functioning as collective systems. The mechanisms underlying the aberrant growth and interactions between cells are not very well understood. The pre-B acute lymphoblastic leukemia cells we studied were obtained directly from a patient with Ph+ ALL. A new Ph+ ALL cell line (ALL3) was established from the leukemic cells growing as ascitic cells in his pleural fluid. The patient died of his disease shortly after the cells were obtained. ALL3 cells grow well at high cell densities (HD), but not at low cell densities...
2016: American Journal of Translational Research
Ashley Rosko, Hai-Lin Wang, Marcos de Lima, Brenda Sandmaier, H Jean Khoury, Andrew Artz, Johnathan Brammer, Christopher Bredeson, Sherif Farag, Mohamed Kharfan-Dabaja, Hillard M Lazarus, David I Marks, Rodrigo Martino Bufarull, Joseph McGuirk, Mohamed Mohty, Taiga Nishihori, Ian Nivison-Smith, Armin Rashidi, Olle Ringden, Matthew Seftel, Daniel Weisdorf, Veronika Bachanova, Wael Saber
: Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older and explored prognostic factors associated with long-term outcomes. METHODS: Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55-72) with B-ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001-2012 using mostly unrelated donor (59%) or HLA-matched sibling (32%)...
October 6, 2016: American Journal of Hematology
Laurence Baranger, Wendy Cuccuini, Christine Lefebvre, Isabelle Luquet, Christine Perot, Isabelle Radford, Marina Lafage-Pochitaloff
Cytogenetic analyses (karyotype and, if necessary, appropriate complementary FISH analyses) are mandatory at diagnosis in acute lymphoblastic leukemia (ALL) as their results are taken into account in therapeutic protocols due to their diagnostic and prognostic values. In some cases, karyotype can be completed by other techniques (RT-PCR, RQ-PCR, DNA content, SNP-array, MLPA…) that can be equally or more informative than FISH. Here, we have tempted to establish guidelines concerning karyotype and FISH analyses according to the most recent data of the litterature which is reviewed here, completing the 2008 WHO classification with the recent new cytogenomic entities such as Ph-like ALL and indicating possible therapeutic implications...
October 1, 2016: Annales de Biologie Clinique
Nikolaos Papadantonakis, Anjali S Advani
This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells...
October 2016: Therapeutic Advances in Hematology
N Gökbuget, M Kelsh, V Chia, A Advani, R Bassan, H Dombret, M Doubek, A K Fielding, S Giebel, V Haddad, D Hoelzer, C Holland, N Ifrah, A Katz, T Maniar, G Martinelli, M Morgades, S O'Brien, J-M Ribera, J M Rowe, A Stein, M Topp, M Wadleigh, H Kantarjian
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial...
2016: Blood Cancer Journal
He Li, Wanhua Zhang, Dongni Yi, Yuanxin Ye, Xueqiu Xiao
No abstract text is available yet for this article.
September 23, 2016: Leukemia & Lymphoma
Jessica T Leonard, Wendy Stock
No abstract text is available yet for this article.
November 2016: Biology of Blood and Marrow Transplantation
Sébastien Maury, Sylvie Chevret, Xavier Thomas, Dominik Heim, Thibaut Leguay, Françoise Huguet, Patrice Chevallier, Mathilde Hunault, Nicolas Boissel, Martine Escoffre-Barbe, Urs Hess, Norbert Vey, Jean-Michel Pignon, Thorsten Braun, Jean-Pierre Marolleau, Jean-Yves Cahn, Yves Chalandon, Véronique Lhéritier, Kheira Beldjord, Marie C Béné, Norbert Ifrah, Hervé Dombret
Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point...
September 15, 2016: New England Journal of Medicine
Daniela Renzi, Francesco Marchesi, Gottardo De Angelis, Loredana Elia, Emanuela Salvatorelli, Svitlana Gumenyuk, Francesca Palombi, Francesco Pisani, Atelda Romano, Antonio Spadea, Elena Papa, Marco Canfora, William Arcese, Andrea Mengarelli
We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment...
September 10, 2016: Chemotherapy
Noura El-Ahmady El-Naggar, Sahar F Deraz, Hoda M Soliman, Nehal M El-Deeb, Sara M El-Ewasy
L-asparaginase is an important enzyme as therapeutic agents used in combination with other drugs in the treatment of acute lymphoblastic leukemia. A newly isolated actinomycetes strain, Streptomyces sp. NEAE-82, was potentially producing extracellular L-asparaginase, it was identified as Streptomyces fradiae NEAE-82, sequencing product was deposited in the GenBank database under accession number KJ467538. L-asparaginase was purified from the crude enzyme using ammonium sulfate precipitation, dialysis and ion exchange chromatography using DEAE Sepharose CL-6B...
2016: Scientific Reports
Nicola Gökbuget, Hervè Dombret, Jose-Maria Ribera, Adele K Fielding, Anjali Advani, Renato Bassan, Victoria Chia, Michael Doubek, Sebastian Giebel, Dieter Hoelzer, Norbert Ifrah, Aaron Katz, Michael Kelsh, Giovanni Martinelli, Mireia Morgades, Susan O' Brien, Jacob M Rowe, Julia Stieglmaier, Martha Wadleigh, Hagop Kantarjian
Adults with relapsed/refractory acute lymphoblastic leukemia have an unfavourable prognosis, which is influenced by disease and patient characteristics. To further evaluate these characteristics, a retrospective analysis of 1,706 adult patients with Ph-negative relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed between 1990-2013 was conducted using data reflecting the standard of care from 11 study groups and large centers in Europe and the United States. Outcomes included complete remission, overall survival, and realization of stem cell transplantation after salvage treatment...
September 1, 2016: Haematologica
Z L Bian, Y J Chang, L P Xu, Y Wang, X H Zhang, K Y Liu, X J Huang
OBJECTIVE: To compare the early stage immune reconstitution of high- and standard-risk Philadelphia chromosome- negative acute lymphoblastic leukemia (ALL) CR1 patients who had haploidentical blood and marrow stem cell transplantation (HBMT). METHODS: A total of 49 Ph-negative ALL CR1 patients who received HBMT and had complete early stage immune reconstitution data(+30, +60 and +90 d post transplantation) from Jan. 2010 to Dec. 2012 were enrolled. Immunophenotyping for B and T lymphocytes was performed post HBMT via flow cytometry...
August 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Jessica T Leonard, Joelle S J Rowley, Christopher A Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E Spurgeon, Brian J Druker, Jeffrey W Tyner, Bill H Chang
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies...
August 31, 2016: Science Translational Medicine
Tobias Herold, Stephanie Schneider, Klaus Metzeler, Martin Neumann, Luise Hartmann, Kathryn G Roberts, Nikola P Konstandin, Philipp A Greif, Kathrin Bräundl, Bianka Ksienzyk, Natalia Huk, Irene Schneider, Evelyn Zellmeier, Vindi Jurinovic, Ulrich Mansmann, Wolfgang Hiddemann, Charles G Mullighan, Stefan K Bohlander, Karsten Spiekermann, Dieter Hölzer, Monika Brüggemann, Claudia D Baldus, Martin Dreyling, Nicola Gökbuget
Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult B-cell precursor ALL (BCP-ALL) patients (median age: 42 years) were classified as Ph-like using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and MLL rearrangements...
August 25, 2016: Haematologica
Ahmet Ulu, Suleyman Koytepe, Burhan Ates
We prepared biodegradable P(MAA-co-MMA)-starch composite as carrier matrix for the immobilization of l-asparaginase (l-ASNase), an important chemotherapeutic agent in acute lymphoblastic leukemia. Chemical characteristics and thermal stability of the prepared composites were determined by FT-IR, TGA, DTA and, DSC, respectively. Also, biodegradability measurements of P(MAA-co-MMA)-starch composites were carried out to examine the effects of degradation of the starch. Then, l-ASNase was immobilized on the P(MAA-co-MMA)-starch composites...
November 20, 2016: Carbohydrate Polymers
Xavier Thomas, Maël Heiblig
In Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL...
November 2016: Expert Opinion on Drug Discovery
Yoshimasa Kamoda, Kiyotaka Izumi, Futoshi Iioka, Takashi Akasaka, Fumihiko Nakamura, Chiyuki Kishimori, Katsuyo Tsuda, Katsuhiro Fukutsuka, Atsuko Okumura, Masahiko Hayashida, Hitoshi Ohno
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-...
2016: Acta Haematologica
Sabina Chiaretti, Antonella Vitale, Marco Vignetti, Alfonso Piciocchi, Paola Fazi, Loredana Elia, Brunangelo Falini, Francesca Ronco, Felicetto Ferrara, Paolo De Fabritiis, Mario Luppi, Giorgio La Nasa, Alessandra Tedeschi, Catello Califano, Renato Fanin, Fausto Dore, Franco Mandelli, Giovanna Meloni, Robin Foa'
In the GIMEMA LAL 0904 protocol, adult Ph+ acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant...
August 11, 2016: Haematologica
Takanobu Morishita, Fumihiko Hayakawa, Keiki Sugimoto, Mizuho Iwase, Hideyuki Yamamoto, Daiki Hirano, Yuki Kojima, Naoto Imoto, Tomoki Naoe, Hitoshi Kiyoi
Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, particularly from the viewpoints of microenvironmental independence. Patient-derived xenografts (PDX) are established by the transfer of primary tumor cells directly from patients into immunodeficient mice and can provide primary-like tumor cells of the amount needed at the desired time. We developed a high-throughput drug screening system using PDX cells and performed drug screening using the PDX cells of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)...
August 2, 2016: Oncotarget
Federico Lussana, Tamara Intermesoli, Francesca Gianni, Cristina Boschini, Arianna Masciulli, Orietta Spinelli, Elena Oldani, Manuela Tosi, Anna Grassi, Margherita Parolini, Ernesta Audisio, Chiara Cattaneo, Roberto Raimondi, Emanuele Angelucci, Irene Maria Cavattoni, Anna Maria Scattolin, Agostino Cortelezzi, Francesco Mannelli, Fabio Ciceri, Daniele Mattei, Erika Borlenghi, Elisabetta Terruzzi, Claudio Romani, Renato Bassan, Alessandro Rambaldi
Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials...
November 2016: Biology of Blood and Marrow Transplantation
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