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Relapsed acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29043149/pre-b-acute-lymphoblastic-leukemia-with-t-1-19-in-an-adult-initially-presenting-as-hematuria-and-bilateral-renal-enlargement-a%C3%A2-case-report-and-literature-review
#1
Jian Wu, Xiao-Ling Pi, Zhi-Bin Ye
Although pre-B acute lymphoblastic leukemia (ALL) is the most common type of renal leukemic infiltration; the renal infiltration with leukemia cells as the initial manifestation of leukemia is very rare. Translocation (1;19)(q23;p13) is one of the most common chromosomal abnormalities in patients with ALL and is observed in 5 - 6% of children with pre-B ALL. However, the incidence of t(1;19) in adults is lower, not exceeding 3%, and the prognosis of adult patients is usually poor. Herein, we report a 52-year-old female patient with pre-B ALL who initially presented as bilateral renal enlargement...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29042995/overexpression-of-dominant-negative-ikaros-6-isoform-is-associated-with-resistance-to-tkis-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#2
Changfeng Shao, Jie Yang, Yirong Kong, Cong Cheng, Wei Lu, Hongzai Guan, Haiyan Wang
The clinical significance of the dominant-negative Ikaros 6 (DN-IK6) in the treatment of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph(+)-ALL) with tyrosine kinase inhibitors (TKIs) remains elusive. In the present study, it was demonstrated that DN-IK6 was overexpressed in B-cell (B)-ALL cases compared with T cell-ALL cases at the mRNA and protein levels. Furthermore, nucleotide sequencing revealed that DN-IK6 was due to the deletion of IKAROS family zinc finger 1 exons 4-7. The outcome of patients with Ph(+)-B-ALL with DN-IK6, and treated with TKIs and hyper-cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen were restrospectively evaluated in a 2 year follow-up...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29040012/outcome-of-acute-lymphoblastic-leukemia-in-children-with-down-syndrome-polish-pediatric-leukemia-and-lymphoma-study-group-report
#3
Joanna Zawitkowska, Teresa Odój, Katarzyna Drabko, Agnieszka Zaucha-Prażmo, Julia Rudnicka, Michał Romiszewski, Michał Matysiak, Kinga Kwiecińska, Magdalena Ćwiklińska, Walentyna Balwierz, Joanna Owoc-Lempach, Katarzyna Derwich, Jacek Wachowiak, Maciej Niedźwiecki, Elżbieta Adamkiewicz-Drożyńska, Joanna Trelińska, Wojciech Młynarski, Andrzej Kołtan, Mariusz Wysocki, Renata Tomaszewska, Tomasz Szczepański, Marcin Płonowski, Maryna Krawczuk-Rybak, Tomasz Ociepa, Tomasz Urasiński, Agnieszka Mizia-Malarz, Grażyna Sobol-Milejska, Grażyna Karolczyk, Jerzy Kowalczyk
Children with Down syndrome (DS) have a 20-fold increased risk of developing leukemia compared with the general population. The aim of the study was to analyze the outcome of patients diagnosed with Down syndrome and acute lymphoblastic leukemia (ALL) in Poland between the years 2003 and 2010. A total of 1848 children were diagnosed with ALL (810 females and 1038 males). Of those, 41 (2.2%) had DS. The children were classified into three risk groups: a standard-risk group-14 patients, an intermediate-risk group-24, a high-risk group-3...
October 17, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29038338/infectious-complications-of-cd19-targeted-chimeric-antigen-receptor-modified-t-cell-immunotherapy
#4
Joshua A Hill, Daniel Li, Kevin A Hay, Margaret L Green, Sindhu Cherian, Xueyan Chen, Stanley R Riddell, David G Maloney, Michael Boeckh, Cameron J Turtle
Lymphodepletion chemotherapy with CD19-targeted chimeric antigen receptor-modified T (CAR-T) cell immunotherapy is a novel treatment for refractory or relapsed B cell malignancies. However, infectious complications of this approach have not been systematically studied. We evaluated infection events occurring between days 0-28 and 29-90 in 133 patients treated with CD19 CAR-T cells in a phase 1/2 study (https://clinicaltrials.gov/ct2/show/NCT01865617). We used multivariable Poisson and Cox regression to evaluate pre- and post-treatment risk factors for infection, respectively...
October 16, 2017: Blood
https://www.readbyqxmd.com/read/29032733/car-t-cells-and-allogeneic-hematopoietic-stem-cell-transplantation-for-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia
#5
Jun Liu, Xi Zhang, Jiang F Zhong, Cheng Zhang
Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL...
October 2017: Immunotherapy
https://www.readbyqxmd.com/read/29032264/building-a-safer-and-faster-car-seatbelts-airbags-and-crispr
#6
REVIEW
Miguel-Angel Perales, Partow Kebriaei, Leslie S Kean, Michel Sadelain
Therapeutic T cell engineering has recently garnered widespread interest owing to the success of CD19 (Chimeric Antigen Receptor) CAR therapy. CARs are synthetic receptors for antigen that redirect the specificity and reprogram the function of the T cells in which they are genetically introduced. CARs targeting CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded high remission rates in patients with chemorefractory, relapsed disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and non-Hodgkin lymphoma...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29025600/a-novel-somatic-jak2-kinase-domain-mutation-in-pediatric-acute-lymphoblastic-leukemia-with-rapid-on-treatment-development-of-loh
#7
Teresa Sadras, Susan L Heatley, Chung H Kok, Barbara J McClure, David Yeung, Timothy P Hughes, Rosemary Sutton, David S Ziegler, Deborah L White
We report a novel somatic mutation in the kinase domain of JAK2 (R938Q) in a high-risk pediatric case of B-cell acute lymphoblastic leukemia (ALL). The patient developed on-therapy relapse at 12 months, and interestingly, the JAK2 locus acquired loss of heterozygosity during treatment resulting in 100% mutation load. Furthermore, we show that primary ALL mononuclear cells harboring the JAK2 R938Q mutation display reduced sensitivity to the JAK1/2 ATP-competitive inhibitor ruxolitinib in vitro, compared to ALL cells that carry a more common JAK2 pseudokinase domain mutation...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025266/the-abcs-of-immunotherapy-for-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#8
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
October 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29018147/acute-lymphoblastic-leukemia-relapse-after-cd19-targeted-chimeric-antigen-receptor-t-cell-therapy
#9
REVIEW
Jiasheng Wang, Yongxian Hu, He Huang
CART19 therapy has revolutionized the treatment of CD19(+) acute lymphoblastic leukemia, demonstrating an unprecedented complete remission rate; however, as follow-up prolongs, a high relapse rate after CART19 therapy has emerged as one of the major problems. Relapse can be attributed to the loss of leukemic cell immunogenicity, diminished function and amount of CART19 cells, and the inhibitory bone marrow microenvironment. Although studies to prevent and treat relapse have begun, some encouraging results have demonstrated the possibility of decreasing the relapse rate...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29018079/setd2-alterations-impair-dna-damage-recognition-and-lead-to-resistance-to-chemotherapy-in-leukemia
#10
Brenton G Mar, S Haihua Chu, Josephine D Kahn, Andrei V Krivstov, Richard Koche, Cecilia A Castellano, Jacob L Kotlier, Rebecca L Zon, Marie E McConkey, Jonathan Chabon, Ryan Chappell, Peter V Grauman, James J Hsieh, Scott A Armstrong, Benjamin L Ebert
Mutations in SETD2, encoding the histone 3 lysine 36 trimethyltransferase, are enriched in relapsed acute lymphoblastic leukemia and MLL rearranged acute leukemia. We investigated the impact of SETD2 mutations on chemotherapy sensitivity in isogenic leukemia cell lines and in murine leukemia generated from a conditional knockout of Setd2SETD2 mutations led to resistance to DNA-damaging agents, cytarabine, 6-thioguanine, doxorubicin, and etoposide, but not to a non-DNA damaging agent, L-asparaginase. H3K36me3 localizes components of the DNA damage response pathway and SETD2 mutation impaired the DNA damage response (DDR), blunting apoptosis induced by cytotoxic chemotherapy...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28991353/asymptomatic-leukemic-optic-nerve-infiltration-as-presentation-of-acute-lymphoblastic-leukemia-relapse
#11
Jane Caty, A Paula Grigorian, Florin Grigorian
The authors report a case of asymptomatic leukemic optic neuropathy as the first sign of acute lymphoblastic leukemia relapse in a 4-year-old boy. Routine ophthalmologic examination showed normal visual acuity and pupillary function in the presence of a tumoral mass covering the left optic disc. The mass resolved with preservation of vision after intrathecal chemotherapy. A routine ophthalmological examination is recommended for all patients with a history of acute lymphoblastic leukemia to exclude optic nerve involvement without systemic symptoms or signs...
October 9, 2017: Journal of Pediatric Ophthalmology and Strabismus
https://www.readbyqxmd.com/read/28990581/blinatumomab-retreatment-after-relapse-in-patients-with-relapsed-refractory-b-precursor-acute-lymphoblastic-leukemia
#12
M S Topp, M Stelljes, G Zugmaier, P Barnette, L T Heffner, T Trippett, J Duell, R C Bargou, C Holland, J E Benjamin, M Klinger, M R Litzow
Leukemia accepted article preview online, 09 October 2017. doi:10.1038/leu.2017.306.
October 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28983949/improved-prognosis-with-additional-medium-dose-vp16-to-cy-tbi-in-allogeneic-transplantation-for-high-risk-all-in-adults
#13
Yasuyuki Arai, Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Michihiro Hidaka, Naoki Kobayashi, Koji Iwato, Toru Sakura, Makoto Onizuka, Yukiyasu Ozawa, Tetsuya Eto, Mineo Kurokawa, Kaoru Kahata, Naoyuki Uchida, Yoshiko Atsuta, Shuichi Mizuta, Shinichi Kako
Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30 - 40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30-40 mg/kg) (N=376) and CY/TBI (N=1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014...
October 6, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28983018/phase-1-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#14
MULTICENTER STUDY
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter phase 1 study was conducted to determine the maximum-tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (N = 55). Moxetumomab pasudotox was administered as a 30-minute IV infusion at doses of 5 to 50 µg/kg every other day for 6 (cohorts A and B) or 10 (cohort C) doses in 21-day cycles...
October 5, 2017: Blood
https://www.readbyqxmd.com/read/28982056/efficacy-and-safety-of-g-csf-low-dose-cytarabine-and-aclarubicin-in-combination-with-l-asparaginase-prednisone-in-the-treatment-of-refractory-or-relapsed-acute-lymphoblastic-leukemia
#15
Keshu Zhou, Yongping Song, Yanli Zhang, Xudong Wei, Yuewen Fu, Fengkuan Yu, Hu Zhou, Xinjian Liu, Jian Zhou, Baijun Fang
Acute lymphoblastic leukemia (ALL) patients who fail to acquire complete remission (CR) or who relapse after initial response have poor prognosis. At present there is no consensus as to the standard salvage therapy for these patients. In this study, we retrospectively evaluate safety and efficacy of a salvage regimen (CAGLP) consisting of G-CSF, low-dose cytarabine, aclarubicin, l-asparaginase and prednisone. Thirty-six patients were included with primary refractory (n=13) or relapse (n=23). The overall response rate (ORR) and CR rate were 86...
September 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28978841/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia
#16
Kiyotoshi Imai
Most patients with adult acute lymphoblastic leukemia (ALL) undergo relapse, despite the achievement of complete remission with chemotherapy. Among patients with relapsed or refractory ALL, remission rates are 18-44% with the use of standard salvage chemotherapy, but the duration of remission is short. A major goal in this population is to induce remission with a sufficient duration to prepare for stem cell transplantation. The poor outcomes and lack of durable responses seen with conventional chemotherapy have led to the development of several novel agents, including clofarabine and nelarabine...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978840/current-treatment-of-adult-acute-lymphoblastic-leukemia
#17
Shin Fujisawa
The survival outcomes for children with acute lymphoblastic leukemia (ALL) have dramatically improved over recent years, and improved outcomes in adolescents and young adults patients have been achieved by applying regimens based on pediatric protocols. The treatment strategies for adult ALL are similar to those for pediatric ALL. T-cell ALL is less common than B-cell ALL. Therefore, there are only few reports of investigations in a large group of adult T-ALL patients. In Japan, nelarabine-combined chemotherapy has been tested in a phase II study in patients with newly diagnosed T-ALL...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28972800/hidden-flt3-d835y-clone-in-flt3-itd-positive-acute-myeloid-leukemia-that-evolved-into-very-late-relapse-with-t-lymphoblastic-leukemia
#18
Seiichiro Katagiri, Tomohiro Umezu, Kenko Azuma, Michiyo Asano, Daigo Akahane, Hideki Makishima, Kenichi Yoshida, Yosaku Watatani, Kenichi Chiba, Satoru Miyano, Seishi Ogawa, Junko H Ohyashiki, Kazuma Ohyashiki
No abstract text is available yet for this article.
October 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28972594/ras-pathway-mutations-as-predictive-biomarker-for-treatment-adaptation-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#19
I S Jerchel, A Q Hoogkamer, I M Ariës, E M P Steeghs, J M Boer, N J M Besselink, A Boeree, C van de Ven, H A de Groot-Kruseman, V de Haas, M A Horstmann, G Escherich, C M Zwaan, E Cuppen, M J Koudijs, R Pieters, M L den Boer
RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods is lacking. Targeted deep sequencing of 13 RAS-pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnosis-relapse pairs. Mutations were present in 44.2% of patients, with 24...
October 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28971751/anti-cd-19-and-anti-cd-20-car-modified-t-cells-for-b-cell-malignancies-a-systematic-review-and-meta-analysis
#20
Irbaz Bin Riaz, Umar Zahid, Muhammad Umar Kamal, Muhammad Husnain, Ali McBride, Anh Hua, Auon Abbas Hamadani, Laeth George, Ali Zeeshan, Qurat-Ul-Ain Riaz Sipra, Ammad Raina, Bushra Rahman, Soham Puvvada, Faiz Anwer
Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195)...
September 2017: Immunotherapy
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