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Relapsed acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/27930631/cd19-targeted-car-t-cells-as-novel-cancer-immunotherapy-for-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukemia
#1
Marco L Davila, Renier J Brentjens
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable...
October 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#2
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
While the emergence of bone marrow-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome positive, acute lymphoblastic leukemia (Ph+ ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and employing them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27920559/e2a-pbx1-exhibited-a-promising-prognosis-in-pediatric-acute-lymphoblastic-leukemia-treated-with-the-cclg-all2008-protocol
#3
Yixin Hu, Hailong He, Jun Lu, Yi Wang, Peifang Xiao, Jianqin Li, Jie Li, Yina Sun, Hui Lv, Junjie Fan, Yanhua Yao, Yihuan Chai, Shaoyan Hu
OBJECTIVE: The objective of this study was to observe the prognosis of pediatric patients with E2A-PBX1-positive acute lymphoblastic leukemia (ALL) from the treatment with the CCLG-ALL2008 protocol. DESIGN AND METHODS: Three hundred and forty-nine Chinese pediatric patients with pre-B-cell ALL were enrolled in this study from December 2008 to September 2013. Of these, 20 patients with E2A-PBX1 expression and 223 without the gene expression were stratified into two cohorts...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27917589/the-petale-study-late-adverse-effects-and-biomarkers-in-childhood-acute-lymphoblastic-leukemia-survivors
#4
Sophie Marcoux, Simon Drouin, Caroline Laverdière, Nathalie Alos, Gregor U Andelfinger, Laurence Bertout, Daniel Curnier, Matthias G Friedrich, Ekaterini A Kritikou, Geneviève Lefebvre, Emile Levy, Sarah Lippé, Valérie Marcil, Marie-Josée Raboisson, Frank Rauch, Philippe Robaey, Mariia Samoilenko, Chantal Séguin, Serge Sultan, Maja Krajinovic, Daniel Sinnett
BACKGROUND: Childhood cancer survivorship issues represent an established public health challenge. Most late adverse effects (LAEs) have been demonstrated to be time and treatment dependent. The PETALE study is a multidisciplinary research project aiming to comprehensively characterize LAEs and identify associated predictive biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors. METHODS: cALL survivors treated at Sainte-Justine University Health Center with Dana-Farber Cancer Institution-ALL protocols 87-01 through 2005-01 were eligible...
December 4, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27916615/characterization-of-rare-dormant-and-therapy-resistant-cells-in-acute-lymphoblastic-leukemia
#5
Sarah Ebinger, Erbey Ziya Özdemir, Christoph Ziegenhain, Sebastian Tiedt, Catarina Castro Alves, Michaela Grunert, Michael Dworzak, Christoph Lutz, Virginia A Turati, Tariq Enver, Hans-Peter Horny, Karl Sotlar, Swati Parekh, Karsten Spiekermann, Wolfgang Hiddemann, Aloys Schepers, Bernhard Polzer, Stefan Kirsch, Martin Hoffmann, Bettina Knapp, Jan Hasenauer, Heike Pfeifer, Renate Panzer-Grümayer, Wolfgang Enard, Olivier Gires, Irmela Jeremias
Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD)...
November 18, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#6
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913531/treatment-of-older-patients-with-acute-lymphoblastic-leukemia
#7
Nicola Gökbuget
The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. With increasing age, ALL patients have a significantly lower clinical remission rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is only partly explained by a higher incidence of poor prognostic factors in the older age group. Most importantly, intensive chemotherapy with or without stem cell transplantation (SCT) is less well tolerated in older patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913530/cytokine-release-syndrome-with-novel-therapeutics-for-acute-lymphoblastic-leukemia
#8
Noelle V Frey, David L Porter
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#9
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27904561/analysis-of-outcomes-and-prognostic-factors-of-acute-lymphoblastic-leukemia-patients-treated-by-mcp841-protocol-a-regional-cancer-center-experience
#10
Akhil Kapoor, Ashok Kalwar, Narender Kumar, Mukesh Kumar Singhal, Surender Beniwal, Harvindra Singh Kumar
BACKGROUND: A dramatic improvement in the survival of acute lymphoblastic leukemia (ALL) patients in the last three decades has been observed. MCP 841 protocol is an old but effective tool with tolerable toxicities. The objective of this study was to estimate the relapse-free survival of ALL patients treated uniformly with MCP 841 protocol on the basis of various prognostic factors. MATERIALS AND METHODS: The study design was retrospective and it was conducted in a regional cancer center of Northwest India...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27899802/genomic-and-transcriptional-landscape-of-p2ry8-crlf2-positive-childhood-acute-lymphoblastic-leukemia
#11
C Vesely, C Frech, C Eckert, G Cario, A Mecklenbräuker, U Zur Stadt, K Nebral, F Kraler, S Fischer, A Attarbaschi, M Schuster, C Bock, H Cavé, A von Stackelberg, M Schrappe, M A Horstmann, G Mann, O A Haas, R Panzer-Grümayer
Children with P2RY8-CRLF2-positive ALL have an increased relapse risk. Their mutational and transcriptional landscape as well as the respective patterns at relapse remains largely elusive. We therefore performed an integrated analysis of whole-exome and RNA-sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895713/coexistence-of-iamp21-and-etv6-runx1-fusion-in-an-adolescent-with-b-cell-acute-lymphoblastic-leukemia-literature-review-of-six-additional-cases
#12
Jun Gu, Alexandra Reynolds, Lianghua Fang, Corrie DeGraffenreid, Kenneth Sterns, Keyur P Patel, L Jeffrey Medeiros, Pei Lin, Xinyan Lu
BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21) results from breakage-fusion-bridge cycles and chromothripsis is a distinct marker of a subgroup of B cell acute lymphoblastic leukemia (B-ALL) cases associated with a poor prognosis. iAMP21 accounts for 2% of pediatric B-ALL and occurs predominantly in older children or adolescents. ETV6-RUNX1 fusion, resulting from t(12;21)(p13;q22), is associated with an excellent outcome in younger children with B-ALL. Coexistence of iAMP21 with ETV6-RUNX1 fusion is extremely rare with limited clinical information available...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27894077/tyrosine-kinase-fusion-genes-in-pediatric-bcr-abl1-like-acute-lymphoblastic-leukemia
#13
Judith M Boer, Elisabeth M P Steeghs, João R M Marchante, Aurélie Boeree, James J Beaudoin, H Berna Beverloo, Roland P Kuiper, Gabriele Escherich, Vincent H J van der Velden, C Ellen van der Schoot, Hester A de Groot-Kruseman, Rob Pieters, Monique L den Boer
Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine kinase-activating lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in children with BCP-ALL, we studied the frequency of recently identified tyrosine kinase fusions, associated genetic features, and prognosis in a representative Dutch/German cohort...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889709/role-of-mid-induction-peripheral-blood-minimal-residual-disease-detection-in-pediatric-b-lineage-acute-lymphoblastic-leukemia
#14
Karthik Bommannan, Man Updesh Singh Sachdeva, Neelam Varma, Parveen Bose, Deepak Bansal
OBJECTIVE: To study the role of mid-induction (day 15) peripheral blood minimal residual disease (PBMRD) detection in pediatric B- lineage acute lymphoblastic leukemia (B-ALL). DESIGN: Prospective. SETTING: Tertiary care center. PATIENTS: Forty consecutively diagnosed treatment naive, pediatric B-ALL patients. INTERVENTION: National Cancer Institute (NCI) standard risk patients were given three drug induction regimen comprising vincristine, L-asparginase and prednisolone; NCI high risk patients were supplemented with daunorubicin...
November 5, 2016: Indian Pediatrics
https://www.readbyqxmd.com/read/27888802/low-dose-triptolide-reverses-chemoresistance-in-adult-acute-lymphoblastic-leukemia-cells-via-reactive-oxygen-species-generation-and-dna-damage-response-disruption
#15
Haijun Zhao, Pengcheng Shi, Manman Deng, Zhiwu Jiang, Yin Li, Vinodh Kannappan, Weiguang Wang, Peng Li, Bing Xu
Chemoresistance represents a major challenge for treatment of acute lymphoblastic leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently needed. To this end, we established a cytarabine (araC)-resistant ALL cell line (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin (ADM). Here we report that low dose of triptolide (TPL), a natural product used for treating inflammatory diseases such as arthritis, could reverse araC and ADM resistance and in NALM-6/R cells as well as primary cells from patients with relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation and induction of apoptosis in vitro, and repression of tumor growth in vivo in a mouse xenograft model...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887660/co-infusion-of-haplo-identical-cd19-chimeric-antigen-receptor-t-cells-and-stem-cells-achieved-full-donor-engraftment-in-refractory-acute-lymphoblastic-leukemia
#16
Bo Cai, Mei Guo, Yao Wang, Yajing Zhang, Jun Yang, Yelei Guo, Hanren Dai, Changlin Yu, Qiyun Sun, Jianhui Qiao, Kaixun Hu, Hongli Zuo, Zheng Dong, Zechuan Zhang, Mingxing Feng, Bingxia Li, Yujing Sun, Tieqiang Liu, Zhiqing Liu, Yi Wang, Yajing Huang, Bo Yao, Weidong Han, Huisheng Ai
BACKGROUND: Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. CASE PRESENTATION: We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#17
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879553/acute-vision-loss-as-the-only-sign-of-leukemia-relapse
#18
Marta Cerdà-Ibáñez, Patricia Bayo-Calduch, Laura Manfreda-Domínguez, Antonio Duch-Samper
PURPOSE: To report a case of unilateral exudative retinal detachment as the sole presentation of relapsing B-type lymphoblastic leukemia in a 35-year-old man after 3 years of remission. METHODS: Case report. RESULTS: A 35-year-old man in complete remission of high-risk type B acute lymphoblastic leukemia (ALL-B) presented with acute vision loss in his left eye. Exudative retinal detachment was diagnosed at initial evaluation. Hematological and ocular studies were performed...
August 23, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27875783/prame-overexpression-predicted-good-outcome-in-pediatric-b-cell-acute-lymphoblastic-leukemia-patients-receiving-chemotherapy
#19
Yan-Huan Zhang, Ai-Dong Lu, Lu Yang, Ling-Di Li, Wen-Min Chen, Ling-Yu Long, Le-Ping Zhang, Ya-Zhen Qin
To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5...
November 11, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27873237/estimating-long-term-survival-of-adults-with-philadelphia-chromosome-negative-relapsed-refractory-b-precursor-acute-lymphoblastic-leukemia-treated-with-blinatumomab-using-historical-data
#20
Arie Barlev, Vincent W Lin, Aaron Katz, Kuolung Hu, Ze Cong, Beth Barber
INTRODUCTION: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years. METHODS: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset...
November 21, 2016: Advances in Therapy
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