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Nelarabine

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https://www.readbyqxmd.com/read/29047158/hyper-cvad-plus-nelarabine-in-newly-diagnosed-adult-t-cell-acute-lymphoblastic-leukemia-and-t-lymphoblastic-lymphoma
#1
Yasmin Abaza, Hagop M Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28978841/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia
#2
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
#3
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/28961308/nelarabine-induced-peripheral-and-central-neurotoxicity-can-sequential-mri-brain-imaging-help-to-define-its-natural-history
#4
Karl Ewins, Andrea Malone, Ethna Phelan, David Webb, J C McHugh, Owen Smith
A 14-year-old boy with relapsed T cell acute lymphoblastic leukaemia received reinduction chemotherapy that included nelarabine, a purine nucleoside analogue known to cause dose-dependent neurotoxicity. Although he achieved aminimal residual disease negative remission after two cycles of chemotherapy he also developed severe, progressive peripheral and central neurotoxicities. Loss of grey-white differentiation was seen on a T2-weighted magnetic resonance imaging brain scan. This unusual clinical picture and previously unreported radiological findings are thought to be due to nelarabine toxicity...
October 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28891074/nelarabine-toxicity-in-children-and-adolescents-with-relapsed-refractory-t-all-t-lbl-can-we-avoid-throwing-the-baby-out-with-the-bathwater
#5
EDITORIAL
Andrea Malone, Owen P Smith
No abstract text is available yet for this article.
October 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28771663/safety-and-efficacy-of-nelarabine-in-children-and-young-adults-with-relapsed-or-refractory-t-lineage-acute-lymphoblastic-leukaemia-or-t-lineage-lymphoblastic-lymphoma-results-of-a-phase-4-study
#6
MULTICENTER STUDY
Christian Michel Zwaan, Jerzy Kowalczyk, Claudine Schmitt, Bella Bielorai, Mark W Russo, Mary Woessner, Sulabha Ranganathan, Guy Leverger
Nelarabine is an antineoplastic agent approved for the treatment of relapsed/refractory T-lineage acute lymphoblastic leukaemia (T-ALL) or T-lineage acute lymphoblastic lymphoma (T-LBL). The purpose of this phase 4, multicentre, single-arm, observational, open-label trial was to provide additional data on the safety and efficacy of nelarabine under licensed conditions of use in children and young adults ≤21 years of age. Patients (N = 28) had a mean ± standard deviation age of 11·5 ± 4·6 years; 71% were male and 61% had a diagnosis of T-ALL...
October 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28771662/neurotoxic-side-effects-in-children-with-refractory-or-relapsed-t-cell-malignancies-treated-with-nelarabine-based-therapy
#7
MULTICENTER STUDY
Michaela Kuhlen, Kirsten Bleckmann, Anja Möricke, Martin Schrappe, Simon Vieth, Gabriele Escherich, Annika Bronsema, Annika Vonalt, Manon Queudeville, C Michel Zwaan, Martin Ebinger, Klaus-Michael Debatin, Thomas Klingebiel, Ewa Koscielniak, Claudia Rossig, Birgit Burkhardt, Reinhard Kolb, Cornelia Eckert, Arndt Borkhardt, Arend von Stackelberg, Christiane Chen-Santel
The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged ≤19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1-2 cycles of Ara-G...
October 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28745456/pediatric-t-all-complicated-by-irreversible-nelarabine-neurotoxicity
#8
Takuyo Kanayama, Toshihiko Imamura, Norio Nakagawa, Shinya Osone, Hajime Hosoi
No abstract text is available yet for this article.
July 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28436707/samhd1-protects-cancer-cells-from-various-nucleoside-based-antimetabolites
#9
Nikolas Herold, Sean G Rudd, Kumar Sanjiv, Juliane Kutzner, Julia Bladh, Cynthia B J Paulin, Thomas Helleday, Jan-Inge Henter, Torsten Schaller
Recently, we demonstrated that sterile α motif and HD domain containing protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemia (AML) cells to the cytotoxicity of cytarabine (ara-C), the most important drug in AML treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis pathway to ara-CTP, which serves as a substrate but not an allosteric activator of SAMHD1. Using an AML mouse model, we show here that wild type but not catalytically inactive SAMHD1 reduces ara-C treatment efficacy in vivo...
June 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28169005/nelarabine-associated-reversible-guillain-barr%C3%A3-like-syndrome-or-myelopathy-in-an-adult-patient-with-primary-refractory-t-lymphoblastic-lymphoma
#10
Chrysavgi Lalayanni, Eirini Baldoumi, Sotiris Papayiannopoulos, Konstantia Tziola, Riad Saloum, Achilles Anagnostopoulos
Nelarabine is a purine analogue used for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma mainly as a bridge to stem cell transplantation. The water-soluble prodrug of 9-beta-D-arabinofuranosyl guanine (Ara-G) is phosphorylated within leukemic cells to form ara-G triphosphate (ara-GTP), which terminates DNA chain elongation, resulting in cell death. The drug received accelerated approval by the US Food and Drug Administration (FDA) on October 2005 based on the induction of complete remissions in 2 phase II trials...
November 17, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28115371/management-of-adults-with-t-cell-lymphoblastic-leukemia
#11
REVIEW
David I Marks, Clare Rowntree
T-cell acute lymphoblastic leukemia (ALL) is a rare disease in adults with inferior survival outcomes compared with those seen in pediatric patients. Although potentially curable with ∼50% survival at 5 years, adult patients with relapsed disease have dismal outcomes with <10% of patients surviving long term. This review will discuss the diagnosis and management of adult patients with newly diagnosed T-cell ALL with an emphasis on the immunophenotypic and genetic analyses required to assign prognosis, risk stratify, and guide post-remission therapy...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/27869523/nelarabine-in-the-treatment-of-pediatric-and-adult-patients-with-t-cell-acute-lymphoblastic-leukemia-and-lymphoma
#12
REVIEW
Tapan M Kadia, Varsha Gandhi
T-cell acute lymphoblastic leukemia (ALL) and lymphoma (LBL) are aggressive hematologic neoplasms that are treated with combination chemotherapy in the frontline, but have limited options in the relapsed or refractory setting. Based on observations in patients with purine nucleoside phosphorylase (PNP) deficiency, a guanosine nucleoside analogue, arabinosylguanine (ara-G) was developed that provided T-cell specificity. Nelarabine was developed as the water-soluble, clinically useful-prodrug of ara-G and based on its activity was approved for the treatment of relapsed or refractory T-ALL/LBL...
January 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/27776559/improving-nelarabine-efficacy-in-t-cell-acute-lymphoblastic-leukemia-by-targeting-aberrant-pi3k-akt-mtor-signaling-pathway
#13
Annalisa Lonetti, Alessandra Cappellini, Alice Bertaina, Franco Locatelli, Andrea Pession, Francesca Buontempo, Camilla Evangelisti, Cecilia Evangelisti, Ester Orsini, Laura Zambonin, Luca Maria Neri, Alberto Maria Martelli, Francesca Chiarini
BACKGROUND: Although in recent years, the introduction of novel chemotherapy protocols has improved the outcome of T cell acute lymphoblastic leukemia (T-ALL) patients, refractory and/or relapsing disease remains a foremost concern. In this context, a major contribution was provided by the introduction of the nucleoside analog nelarabine, approved for salvage treatment of T-ALL patients with refractory/relapsed disease. However, nelarabine could induce a life-threatening, dose-dependent neurotoxicity...
October 24, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27576612/gene-expression-ratio-as-a-predictive-determinant-of-nelarabine-chemosensitivity-in-t-lymphoblastic-leukemia-lymphoma
#14
Pornpun Sripornsawan, Yasuhiro Okamoto, Takuro Nishikawa, Yuichi Kodama, Yuni Yamaki, Koichiro Kurauchi, Takayuki Tanabe, Shunsuke Nakagawa, Yuichi Shinkoda, Naoko Imuta, Yoshifumi Kawano
BACKGROUND: Nelarabine has been used for the treatment of T-cell malignancies including T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma. However, the mechanisms that underlie the susceptibility or resistance to nelarabine have not been fully elucidated. The aim of this study was to determine the significance of nelarabine transport and metabolism in the context of nelarabine cytotoxicity. PROCEDURE: The expression profiles of six genes in the nelarabine pathway were analyzed in blast cells from six patients with T-ALL as well as in three T-ALL cell lines...
February 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27268298/lineage-switch-with-t-6-11-q27-q23-from-t-cell-lymphoblastic-lymphoma-to-acute-monoblastic-leukemia-at-relapse
#15
Yusuke Higuchi, Kenji Tokunaga, Yuko Watanabe, Toshiro Kawakita, Naoko Harada, Shunichiro Yamaguchi, Kisato Nosaka, Hiroaki Mitsuya, Norio Asou
We present a patient with T-cell lymphoblastic lymphoma (T-LBL) harboring t(6;11)(q27;q23) that converted to acute monoblastic leukemia at relapse. A 27-year-old man developed T-LBL with a mediastinal mass. He exhibited several recurrences in the central nervous system and marrow. A fifth relapse occurred in the marrow, with 42.8% blasts with CD4, CD5, CD7, CD10, CD33, CD34, HLA-DR and cytoplasmic (cy) CD3. While achieving complete remission with nelarabine, sixth relapse occurred in the marrow with 6.8% blasts, which had characteristics of monoblastic features, 2 months later...
2016: Cancer Genetics
https://www.readbyqxmd.com/read/26899359/mr-imaging-in-nelarabine-induced-myelopathy
#16
REVIEW
Sumeet G Dua, Miral D Jhaveri
Nelarabine is one of the newer and novel drugs approved by the USA Food and Drug Administration for treatment of relapsed and resistant acute lymphoblastic leukemia. Although there are a few accounts of the neurologic toxicity of nelarabine in the oncological literature, it has never been discussed from a radiologic stand point to our knowledge. We describe a case of nelarabine-induced myelopathy and review the existing literature in an attempt to characterize the MRI features helpful in making an early diagnosis of this elusive entity...
July 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/26369814/base-modified-nucleosides-as-chemotherapeutic-agents-past-and-future
#17
REVIEW
Matthew P Burke, Kayla M Borland, Vladislav A Litosh
Nucleoside and nucleobase antimetabolites have substantially impacted treatment of cancer and infections. Their close resemblance to natural analogs gives them the power to interfere with a variety of intracellular targets, which on one hand gives them high potency, but on the other hand incurs severe side effects, especially of the chemotherapeutics used against malignancies. Therefore, the development of novel nucleoside analogs with widened therapeutic windows represents an attractive target to synthetic organic and medicinal chemists...
2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/26293208/coma-associated-with-nelarabine-in-an-elderly-patient-with-t-cell-acute-lymphoblastic-leukemia-and-severe-chronic-renal-disease
#18
LETTER
Tomohiro F Nishijima, Thomas C Shea, William A Wood, Peter M Voorhees, Katarzyna Jamieson
No abstract text is available yet for this article.
2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/25966988/how-i-treat-adults-with-relapsed-or-refractory-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia
#19
Noelle V Frey, Selina M Luger
The long-term prognosis of adult patients with relapsed Philadelphia chromosome-negative acute lymphoblastic lymphoma (ALL) is poor. Allogeneic stem cell transplant in second remission is the only curative approach and is the goal when feasible. There is no standard chemotherapy regimen for relapsed disease, although a few agents are approved for use in this setting. The bispecific CD19-directed CD3 T-cell engager, blinatumomab, has recently been granted accelerated approval by the US Food and Drug Administration for relapsed or refractory disease of B-cell lineage...
July 30, 2015: Blood
https://www.readbyqxmd.com/read/25966987/how-i-treat-t-cell-acute-lymphoblastic-leukemia-in-adults
#20
Mark R Litzow, Adolfo A Ferrando
T-cell immunophenotype of acute lymphoblastic leukemia (T-ALL) is an uncommon aggressive leukemia that can present with leukemic and/or lymphomatous manifestations. Molecular studies are enhancing our understanding of the pathogenesis of T-ALL, and the discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation. The use of pediatric intensive combination chemotherapy regimens in adolescents and young adults has significantly improved the outcome of patients with T-ALL...
August 13, 2015: Blood
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