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refractory acute leukemia

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https://www.readbyqxmd.com/read/28454312/treatment-with-a-selenium-platinum-compound-induced-t-cell-acute-lymphoblastic-leukemia-lymphoma-cells-apoptosis-through-the-mitochondrial-signaling-pathway
#1
Feifei Wu, Wei Cao, Huaping Xu, Mingxia Zhu, Jing Wang, Xiaoyan Ke
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive hematological disorder that is sensitive to chemotherapy; however, it exhibits frequent relapse rates. Platinum-containing therapeutics are the first-line salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium-containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer properties have been poorly investigated. In the present study, the Cell Counting Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt on cell viability...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453885/lineage-switch-under-blinatumomab-treatment-of-relapsed-common-acute-lymphoblastic-leukemia-without-mll-rearrangement
#2
Annabelle Zoghbi, Udo Zur Stadt, Beate Winkler, Ingo Müller, Gabriele Escherich
Blinatumomab is a bispecific T-cell engaging αCD19 antibody used in refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL). Recently, lineage switch to a myeloid phenotype has been described following CD19 targeting treatment in three pediatric patients with mixed lineage leukemia (MLL) rearranged ALL. We report the case of a female who received blinatumomab for a first relapse of ALL without MLL alterations. She suffered from a second relapse early after hematopoietic stem cell transplantation and was treated with blinatumomab again...
April 28, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28449314/characterization-of-the-anti-cd22-targeted-therapy-moxetumomab-pasudotox-for-b-cell-precursor-acute-lymphoblastic-leukemia
#3
Ichiko Kinjyo, Ksenia Matlawska-Wasowska, Xiaoru Chen, Noel R Monks, Patricia Burke, Stuart S Winter, Bridget S Wilson
Moxetumomab pasudotox is a second-generation recombinant immunotoxin against CD22 on B-cell lineages. Antileukemic activity has been demonstrated in children with chemotherapy-refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), with variable responses. Here, we report in vitro and in vivo evaluation of moxetumomab pasudotox treatment of human cell lines and patient-derived cells as a preliminary study to understand characteristics of sensitivity to treatment. Binding, internalization, and apoptosis were evaluated using fluorescently tagged moxetumomab pasudotox...
April 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28446272/-efficacy-comparison-of-different-salvage-treatment-regimens-for-patients-with-refractory-relapsed-acute-myeloid-leukemia
#4
Wen-Hui Gao, Hong-Min Li, Jing-Yi Yu, Ya-Li Zheng, Li-Hua Wu, Qing-Guo Liu, Jun-Fan Li, Chun-Hua Liu, Yi-Ming Hu, Ning Xu, Shang-Zhu Li, Ying-Chang Mi, Ping-Ping Huang
OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445872/successful-management-of-decitabine-prior-to-full-dose-idarubicin-and-cytarabine-in-the-treatment-of-refractory-recurrent-acute-myeloid-leukemia
#5
Hongyu Zhao, Li Xu, Yongjian Yang, Jianhua Shao, Ping Chen, Xuebin Dong, Linping Gu, Daqi Li
AIMS: To investigate the safety and efficacy of the triple therapy of decitabine, idarubicin, and cytarabine in the treatment of refractory or recurrent acute myeloid leukemia (R/R AML). METHODS: We conducted a single-center retrospective study in which decitabine treatment was administered prior to full-dose idarubicin and cytarabine (D-IA) for 21 R/R AML patients. RESULTS: After 1 cycle of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21 (9...
April 27, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28441264/cd19-isoforms-enabling-resistance-to-cart-19-immunotherapy-are-expressed-in-b-all-patients-at-initial-diagnosis
#6
Jeannette Fischer, Claudia Paret, Khalifa El Malki, Francesca Alt, Arthur Wingerter, Marie A Neu, Bettina Kron, Alexandra Russo, Nadine Lehmann, Lea Roth, Eva-M Fehr, Sebastian Attig, Alexander Hohberger, Thomas Kindler, Jörg Faber
B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy...
April 24, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28428443/mechanisms-of-pinometostat-epz-5676-treatment-emergent-resistance-in-mll-rearranged-leukemia
#7
Carly T Campbell, Jessica N Haladyna, David A Drubin, Ty M Thomson, Michael J Maria, Taylor Yamauchi, Nigel J Waters, Edward J Olhava, Roy M Pollock, Jesse J Smith, Robert A Copeland, Stephen J Blakemore, Kathrin M Bernt, Scott R Daigle
DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28419965/chidamide-in-flt3-itd-positive-acute-myeloid-leukemia-and-the-synergistic-effect-in-combination-with-cytarabine
#8
Xia Li, Xiao Yan, Wenjian Guo, Xin Huang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Yu Xu, ShuJuan Huang, Chenying Li, Yile Zhou, Jie Jin
Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28413717/advances-of-cd19-directed-chimeric-antigen-receptor-modified-t-cells-in-refractory-relapsed-acute-lymphoblastic-leukemia
#9
REVIEW
Guoqing Wei, Lijuan Ding, Jiasheng Wang, Yongxian Hu, He Huang
Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#10
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28406385/retrospective-chart-review-of-hospitalizations-and-costs-associated-with-the-treatment-of-adults-with-philadelphia-negative-b-cell-relapsed-or-refractory-acute-lymphoblastic-leukemia-in-belgium
#11
Johan Maertens, Carlos Graux, Dimitri Breems, Violaine Havelange, Sebastian Wittnebel, Daniëlle Strens, Caroline Hoefkens
OBJECTIVES: To quantify hospitalizations and costs among adults with Philadelphia-negative relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) who received current salvage chemotherapies in Belgium. METHODS: A retrospective chart review identified patients aged ≥18 years and hospitalized between 2005 and 2015 for Ph-negative R/R B-cell ALL. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up...
April 13, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28401497/bortezomib-combined-with-standard-induction-chemotherapy-in-japanese-children-with-refractory-acute-lymphoblastic-leukemia
#12
Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita, Tadashi Ariga, Yosuke Hosoya, Shinsuke Hirabayashi, Atsushi Manabe, Keisuke Hara, Tetsuya Aiba, Tsugumi Shiokawa, Hiroko Tada, Norihiro Sato
Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study...
April 11, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28396160/allogeneic-hematopoietic-cell-transplantation-hct-for-adult-t-cell-acute-lymphoblastic-leukemia-t-all
#13
Betty Ky Hamilton, Lisa Rybicki, Donna Abounader, Kehinde Adekola, Anjali Advani, Ibrahim Aldoss, Veronika Bachanova, Asad Bashey, Stacey Brown, Marcos DeLima, Steven Devine, Christopher R Flowers, Siddharth Ganguly, Madan Jagasia, Vanessa E Kennedy, Dennis Dong Hwan Kim, Joseph McGuirk, Vinod Pullarkat, Rizwan Romee, Karamjeet Sandhu, Melody Smith, Masumi Ueda, Auro Viswabandya, Khoan Vu, Sarah Wall, Simon B Zeichner, Miguel-Angel Perales, Navneet S Majhail
Allogeneic hematopoietic cell transplantation (HCT) is recommended for T-cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and in high risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multi-center retrospective cohort study using data from 208 adult patients transplanted from 2000-2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. Median age at HCT was 37 years and the majority of patients were transplanted in CR, using total body irradiation (TBI) based myeloablative conditioning regimens...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28395942/ex-vivo-t-cell-depleted-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-the-search-for-an-optimum-transplant-t-cell-dose-and-t-cell-add-back-strategy
#14
Prathima Anandi, Xin Tian, Sawa Ito, Pawel Muranski, Puja D Chokshi, Noelle Watters, Upneet Chawla, Nancy Hensel, David F Stroncek, Minoo Battiwalla, A John Barrett
BACKGROUND: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10(4)/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10(7)/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT...
April 7, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28395439/-the-guidelines-for-diagnosis-and-treatment-of-acute-myelogenous-leukemia-relapse-refractory-in-china-2017
#15
(no author information available yet)
No abstract text is available yet for this article.
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28380463/wnt5a-and-ccl25-promote-adult-t-cell-acute-lymphoblastic-leukemia-cell-migration-invasion-and-metastasis
#16
Xinzhou Deng, Zhenbo Tu, Meng Xiong, Kingsley Tembo, Lu Zhou, Pan Liu, Shan Pan, Jie Xiong, Xiangyong Yang, Jun Leng, Qian Zhang, Ruijing Xiao, Qiuping Zhang
Adult T-cell acute lymphoblastic leukemia (T-ALL) is a refractory leukemia. We previously showed that CCL25/CCR9 promotes T-ALL metastasis. In the present study, we assessed the effects of CCL25 on Wnt expression and the effects of Wnt5a and CCL25 on PI3K/Akt and RhoA activation. Transwell assays and mouse xenograft experiments were utilized to assess the effects of Wnt5a and CCL25 on MOLT4 cell invasion, migration and metastasis. The effects of Wnt5a on MOLT4 cell actin polarization and pseudopodium formation were examined using laser scanning confocal microscopy and scanning electron microscopy...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379283/blinatumomab-blincyto%C3%A2-lessons-learned-from-the-bispecific-t-cell-engager-bite%C3%A2-in-acute-lymphocytic-leukemia-all
#17
Greg Friberg, David Reese
BiTE® antibody constructs are single-chain bispecific antibodies with specificity for CD3 on the T cell and a selected surface antigen on a tumor cell. When infused into patients, they are capable of eliciting a polyclonal T cell response that is unrestricted by T cell receptor specificity, presence of MHC class, or additional T cell co-stimuli. The most clinically advanced is the CD19/CD3 construct blinatumomab (Blincyto®), which is approved in the US and EU for relapsed and refractory Philadelphia negative B-cell precursor ALL...
March 31, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28378367/clonal-evolution-detected-with-conventional-cytogenetic-analysis-is-a-potent-prognostic-factor-in-adult-patients-with-relapsed-aml
#18
Hiroaki Shimizu, Akihiko Yokohama, Takuma Ishizaki, Nahoko Hatsumi, Satoru Takada, Takayuki Saitoh, Toru Sakura, Yoshihisa Nojima, Hiroshi Handa
We retrospectively investigated 144 patients with relapsed acute myeloid leukemia (AML) to clarify predisposing factors and the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) at the first relapse. Additional cytogenetic abnormalities are recognized as clonal evolution at the cytogenetic level. Fifty-nine patients (41%) acquired ACA at the first relapse. The incidences of ACA acquisition varied depending on cytogenetic abnormalities at initial diagnosis. Multivariate analysis identified t(8;21), complex karyotype, and a duration of fewer than 12 months of complete remission as independent predisposing factors for ACA acquisition...
April 4, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28370201/a-phase-1-study-of-amg-900-an-orally-administered-pan-aurora-kinase-inhibitor-in-adult-patients-with-acute-myeloid-leukemia
#19
Hagop M Kantarjian, Michael W Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F Chow, Greg Friberg, Florian D Vogl, Mikkael A Sekeres
Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small-molecule inhibitor of both Aurora kinase A and B, in patients with AML. Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every-2-week dose-escalation schedules using a modified 3 + 3+3 design were used: AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule)...
March 28, 2017: American Journal of Hematology
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
#20
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
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