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Acute T Lymphoblastic Leukemia

María Sol Brassesco, Elvis Terci Valera, Claus Meyer, Rolf Marschalek, Bruno Almeida Lopes, Rosane Gomes de Paula Queiroz, Rodrigo de Tocantins Calado, Carlos Alberto Scrideli, Luiz Gonzaga Tone
We present a case of an infant who developed pro-B acute lymphoblastic leukemia with a rare and complex MLL-translocation. Cytogenetic analysis of bone marrow cells at diagnosis showed a 46,XY,t(X;11)(p11.2;q23)[13]/46,XY[7] karyotype. Fluorescence in situ hybridization analysis using a break apart specific probes showed a split in the MLL gene. Long distance inverse-PCR and next generation sequencing analysis depicted a complex rearrangement t(X;11;17)(p11.2;q23;q12) involving MLL, MLLT6 and the genomic region Xp11...
December 2018: Cancer Genetics
S Modvig, H O Madsen, S M Siitonen, S Rosthøj, A Tierens, V Juvonen, L T N Osnes, H Vålerhaugen, M Hultdin, I Thörn, R Matuzeviciene, M Stoskus, M Marincevic, L Fogelstrand, A Lilleorg, N Toft, O G Jónsson, K Pruunsild, G Vaitkeviciene, K Vettenranta, B Lund, J Abrahamsson, K Schmiegelow, H V Marquart
Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3 ) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99...
December 14, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jinfeng Xiang, Gang Wang, Tian Xia, Zhixin Chen
Mutation of PHF6 has been identified in Börjeson-Forssman-Lehmann syndrome and some types of subsets of childhood leukemia. However, the molecular function and the relationship of PHF6 mutation with glucocorticoid drug resistance during T-ALL treatment remains elusive. Here we report the influence of PHF6 expression on the drug response of T-ALL to prednisolone, and the underlying mechanism of this. Through sanger sequencing and western blotting assays, we identified two T-ALL cell lines with wild-type PHF6 expression, including SIL-ALL and CCRF-CEM, and two T-ALL cell lines without PHF6 expression, including TALL-1 and HPB-ALL, due to the nonsense and frameshift mutations in the coding region of PHF6...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Reith R Sarkar, Nicholas J Gloude, Deborah Schiff, James D Murphy
Background: Chimeric antigen receptor T-cell (CAR-T) therapy is a promising new class of cancer therapy but has a high up-front cost. We evaluated the cost-effectiveness of CAR-T therapy among pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Methods: We built a microsimulation model for pediatric patients with relapsed/refractory B-ALL receiving either CAR-T therapy or standard of care. Outcomes included costs, quality of life (health utility), complications, and survival...
December 14, 2018: Journal of the National Cancer Institute
J Prinz, Y d'Hargues, P Gödel, A Shimabukuro-Vornhagen, M Kochanek, B Böll
BACKGROUND: The development of chimeric antigen receptor (CAR) T‑cells has shown promising results in relapsed/refractory B‑cell acute lymphoblastic leukemia/lymphoma (B-ALL) and diffuse large cell B‑cell lymphoma. Complications, especially cytokine release syndrome (CRS) and CAR T‑cell related encephalopathy syndrome (CRES), can be life threatening. The management of both plays a key role in CAR T‑cell therapy. OBJECTIVES: Diagnosis, clinical presentation and development of complications in the treatment with CAR T‑cells...
December 13, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Umit Y Malkan, Gursel Gunes, Haluk Demiroglu, Hakan Goker
Posterior reversible encephalopathy syndrome (PRES) was described in 1996. Herein, we aimed to report an immunosuppression- related PRES case. A 34-year-old woman was diagnosed as t-cell acute lymphoblastic leukemia and allogeneic hematopoietic stem cell transplantation (HSCT) was performed. Cyclosporine was given for GVHD prophylaxis in addition to the other routine medications of HSCT. She was hospitalized for acute renal failure and due to the possible contribution of acute renal failure cyclosporine was stopped...
November 6, 2018: Hematology Reports
Christopher Kim, Julia T Molony, Victoria M Chia, Vamsi K Kota, Aaron J Katz, Shuling Li
To describe patient characteristics and treatment patterns among elderly patients (≥66 years) newly diagnosed with acute lymphoblastic leukemia (ALL), we analyzed 100% Medicare ALL data from 2007 to 2015. Only 764 out of 1428 (53.5%) elderly patients received treatment within 90 d of diagnosis with ≥30-d follow-up; 32.4% received chemotherapy without tyrosine kinase inhibitors (TKIs), 8.8% received both chemotherapy and TKIs, 9.8% received steroids only and 2.6% received TKIs only. Among 717 patients receiving chemotherapy any time during follow-up, 65...
December 13, 2018: Leukemia & Lymphoma
Keichiro Mihara, Tetsumi Yoshida, Joyeeta Bhattacharyya
Chimeric antigen receptors against CD19 (anti-CD19-CAR) are widely recognized and used by not only researchers associated with immunology, molecular biology, and cell biology but also physicians to treat B-cell malignancies. Anti-CD19-CAR is currently clinically available as one of the therapeutic modalities for refractory acute B-cell-typed lymphoblastic leukemia (B-ALL) patients. However, to detect CAR on the cell surface and investigate the efficacy of CAR-T cells, there are numerous experimental modalities including flow cytometry, the Cr-releasing assay, immunoblot, and immunostaining...
2019: Methods in Molecular Biology
J Gao, W-J Liu
OBJECTIVE: To systematically review prednisone induced test results in the prognosis assessment of acute lymphoblastic leukemia in children. MATERIALS AND METHODS: Based on the established inclusion and exclusion criteria, studies of prednisone induced test in evaluating the prognosis of childhood acute lymphoblastic leukemia were electronically searched from January 1990 to November 2016 using Pubmed, Embase, The Cochrane Library, Web of Science, WanFang, VIP, and CNKI database...
November 2018: European Review for Medical and Pharmacological Sciences
Min Jiang, Xueqin Zou, Lingyun Lu
Acute B‑cell lymphoblastic leukemia (B‑ALL) is a common type of blood cancer, which is associated with aberrant gene expression. Cytokine receptor‑like factor 2 (CRLF2) serves a crucial role in the growth and allergic and inflammatory responses of dendritic cells and T cells. The purpose of the present study was to investigate the potential therapeutic and prognostic effect of silencing the CRLF2‑mediated RAC‑α serine/threonine‑protein kinase (AKT)/serine/threonine‑protein kinase mTOR (mTOR) pathway in B‑ALL...
December 7, 2018: Oncology Reports
Z Takki Chebihi, A Belkhayat, E Chadli, L Hessissen, M El Khorassani, M El Kababri, A Kili, M Khattab, Y Bakri, N Dakka
Cytogenetic studies of acute lymphoblastic leukemia have been at the forefront of research in the pathogenesis of cancer. The presence of recurring chromosomal abnormalities (either numeral or structural rearrangements) provides immediate clues to the genetic events leading to leukemia and many abnormalities have important prognostic significance. The rare translocation t(14,21)(q11.2;q22) has been described in pediatric T lineage ALL in only one case so far in 2000. The present study is a case report of an ALL case in which we found a t(14,21)(q11...
2019: Leukemia Research Reports
Jen-Sheng Pei, Wen-Shin Chang, Pei-Chen Hsu, Chao-Chun Chen, Shun-Ping Cheng, Yun-Chi Wang, Chia-Wen Tsai, Te-Chun Shen, Da-Tian Bau
Purpose: A growing body of evidence shows an association between DNA repair protein genotypes and susceptibility to various cancers. However, few studies have assessed the contribution of the genotype of XRCC3 , a homologous repair gene, to the occurrence or prognosis of childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the contribution of seven XRCC3 polymorphisms to childhood ALL. Patients and methods: We recruited 266 patients with childhood ALL and 266 healthy controls...
2018: Cancer Management and Research
Sabrina Traxel, Linda Schadt, Tatjana Eyer, Vanessa Mordasini, Claudine Gysin, Ludvig A Munthe, Felix Niggli, David Nadal, Simone Bürgler
Precursor B cell acute lymphoblastic leukemia (BCP-ALL) constitutes the leading cause of cancer-related death in children. While chromosomal alterations contribute to BCP-ALL pathogenesis, they are insufficient for leukemia development. Epidemiological data and evidence from a mouse model suggest that immune responses to infections may trigger the emergence of leukemia, but the mechanisms remain unclear. Here, we show that T helper (Th) cells from bone marrow of pediatric BCP-ALL patients can be attracted and activated by autologous BCP-ALL cells...
December 7, 2018: Oncogene
Yo-Taro Shirai, Anna Mizutani, Saori Nishijima, Masafumi Horie, Chisato Kikuguchi, Olga Elisseeva, Tadashi Yamamoto
Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT complex, is found to be associated with T-cell acute lymphoblastic leukemia, T-ALL, though its contribution to other cancers has not been reported. Here, we provide evidence suggesting that CNOT3 is required for the growth of non-small cell lung cancer...
December 10, 2018: Oncogene
Jennifer N Brudno, James N Kochenderfer
Chimeric antigen receptor (CAR) T-cell therapy is an effective new treatment for hematologic malignancies. Two CAR T-cell products are now approved for clinical use by the U.S. FDA: tisagenlecleucel for pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma subtypes (DLBCL), and axicabtagene ciloleucel for DLBCL. CAR T-cell therapies are being developed for multiple myeloma, and clear evidence of clinical activity has been generated. A barrier to widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) and neurologic toxicity...
November 14, 2018: Blood Reviews
Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin
Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4 -Erucoyl spermidine (designed as N4 -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown...
2018: Epigenetics insights
Charles E de Bock, Michelle Down, Kinsha Baidya, Bram Sweron, Andrew W Boyd, Mark Fiers, Gordon F Burns, Timothy J Molloy, Richard B Lock, Jean Soulier, Tom Taghon, Pieter Van Vlierberghe, Jan Cools, Jeff Holst, Rick F Thorne
No abstract text is available yet for this article.
December 4, 2018: Haematologica
Tania Jain, Mark R Litzow
Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Michael A Pulsipher
Multicenter trials in children and young adults using second-generation CD19-targeted chimeric antigen receptor (CAR) T cells have shown dramatic levels of remission in patients with multiply relapsed/refractory disease (80% to ≥90%). Early results in adult trials have also shown significant responses, and strategies aimed at mitigating toxicities associated with the therapy have improved tolerability. Therefore, if available, CAR T-cell therapy deserves consideration for salvage of children and adults with B-lineage acute lymphoblastic leukemia (B-ALL) who are multiply relapsed, refractory, or relapsed after a previous allogeneic transplantation...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Shira Dinner, Michaela Liedtke
The use of multiagent combination chemotherapy regimens results in cure rates of >90% for children and ∼40% for adults with acute lymphoblastic leukemia (ALL) but is associated with extensive toxicity and disappointingly low efficacy in relapsed patients. ALL blast cells express several surface antigens, including CD20, CD22, and CD19, which represent valuable targets for immunotherapy. Monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell-engaging antibodies targeting these antigens offer novel mechanisms of action...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
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