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Relapsed acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29222264/incorporation-of-nonchemotherapeutic-agents-in-pediatric-acute-lymphoblastic-leukemia
#1
REVIEW
Lewis B Silverman
With current available therapies, the prognosis for most children and adolescents with acute lymphoblastic leukemia (ALL) is favorable. However, the multiagent chemotherapy regimens used to treat newly diagnosed patients are associated with many acute and long-term complications, and therapy for relapsed disease is intensive and suboptimally effective. Over the last decade, several nonchemotherapeutic approaches have been evaluated, with the goal of identifying more effective, less toxic therapies that can be used in conjunction with, or even replace, current regimens...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222263/crisis-management-in-the-treatment-of-childhood-acute-lymphoblastic-leukemia-putting-right-what-can-go-wrong-emergency-complications-of-disease-and-treatment
#2
REVIEW
Rachael Hough, Ajay Vora
The improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the "burden of therapy" in an increasing number of survivors...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222234/progress-in-adult-all-incorporation-of-new-agents-to-frontline-treatment
#3
REVIEW
Jessica Leonard, Wendy Stock
Treatment of acute lymphoblastic leukemia (ALL) in adults remains a challenge, as the delivery of intensive chemotherapeutic regimens in this population is less feasible than it is in the pediatric population. This has led to higher rates of treatment-related toxicity as well as lower overall survival in the adult population. Over the past several years, a host of novel therapies (eg, immunotherapy and targeted therapies) with better tolerability than traditional chemotherapy are now being introduced into the relapsed/refractory population with very encouraging results...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222233/current-management-of-philadelphia-chromosome-positive-all-and-the-role-of-stem-cell-transplantation
#4
REVIEW
Farhad Ravandi
Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222232/minimal-residual-disease-in-adult-all-technical-aspects-and-implications-for-correct-clinical-interpretation
#5
REVIEW
Monika Brüggemann, Michaela Kotrova
Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29212976/-congenital-leukemia-showing-lineage-switch-following-induction-chemotherapy-and-attaining-long-term-remission-after-hla-haploidentical-stem-cell-transplantation
#6
Kazuki Furudate, Yuri Okimoto, Kumiko Ando, Yuichi Taneyama, Hidemasa Ochiai, Harumi Kakuda
Congenital leukemia is a rare subgroup of childhood leukemia. Lineage switches in leukemic cells are relatively rare events, which have been occasionally reported in congenital leukemia. To the best of our knowledge, the survival of congenital leukemia patients with lineage switch has not been previously documented. This lack of documentation may be attributable to extremely poor prognosis of these patients. We describe a case of a newborn female with initial diagnosis of MLL-AF4 positive B-precursor acute lymphoblastic leukemia, who developed lineage switch to acute monocytic leukemia following the induction therapy...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29210366/outcome-of-relapsed-infant-acute-lymphoblastic-leukemia-treated-on-the-interfant-99-protocol
#7
E M C Driessen, P de Lorenzo, M Campbell, M Felice, A Ferster, I Hann, A Vora, L Hovi, G Escherich, C K Li, G Mann, T Leblanc, F Locatelli, A Biondi, J Rubnitz, M Schrappe, L Silverman, J Stary, R Suppiah, T Szczepanski, M Valsecchi, R Pieters
This corrects the article DOI: 10.1038/leu.2015.246.
December 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29209600/targeting-flt3-signaling-in-childhood-acute-myeloid-leukemia
#8
REVIEW
Amy N Sexauer, Sarah K Tasian
Acute myeloid leukemia (AML) is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3) occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29200159/posterior-reversible-encephalopathy-syndrome-risk-factors-and-impact-on-the-outcome-in-children-with-acute-lymphoblastic-leukemia-treated-with-nordic-protocols
#9
Joanna S Banerjee, Mats Heyman, Maarit Palomäki, Päivi Lähteenmäki, Mikko Arola, Pekka V Riikonen, Merja I Möttönen, Tuula Lönnqvist, Mervi H Taskinen, Arja H Harila-Saari
Posterior reversible encephalopathy syndrome (PRES) in children with acute lymphoblastic leukemia has been increasingly recognized as a clinicoradiological entity. Our aim was to describe the incidence of PRES in pediatric patients with ALL, identify its risk factors, and examine its prognostic importance. For this research, we conducted a systematic, retrospective review of the patient records in a population-based series of children with acute lymphoblastic leukemia (n=643) treated in Finland from 1992 to 2008...
December 1, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29197676/intravenous-busulfan-compared-to-total-body-irradiation-pre-transplant-conditioning-for-adults-with-acute-lymphoblastic-leukemia
#10
Partow Kebriaei, Claudio Anasetti, Mei-Jie Zhang, Hai-Lin Wang, Ibrahim Aldoss, Marcos de Lima, H Jean Khoury, Brenda M Sandmaier, Mary M Horowitz, Andrew Artz, Nelli Bejanyan, Stefan Ciurea, Hillard M Lazarus, Robert Peter Gale, Mark Litzow, Christopher Bredeson, Matthew D Seftel, Michael A Pulsipher, Jaap-Jan Boelens, Joseph Alvarnas, Richard Champlin, Stephen Forman, Vinod Pullarkat, Daniel Weisdorf, David I Marks
Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (BU) to decrease toxicity. This retrospective study analyzed TBI and BU on outcomes of ALL patients aged 18-60 years, in first or second complete remission (CR), undergoing HLA-compatible sibling, related or unrelated donor HCT, reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29191665/augmenting-total-body-irradiation-with-a-cranial-boost-before-stem-cell-transplantation-protects-against-post-transplant-cns-relapse-in-acute-lymphoblastic-leukemia
#11
Robert W Gao, Kathryn E Dusenbery, Qing Cao, Angela R Smith, Jianling Yuan
PURPOSE: The purpose of this study was to determine the effect of a pre-transplant cranial boost (CB) on post-transplant central nervous system (CNS) relapse and survival in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using a total body irradiation (TBI)-containing preparation regimen. METHODS AND MATERIALS: Two hundred thirteen ALL patients were treated consecutively at our institution with allogeneic HSCT...
November 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29189615/multi-modal-treatment-of-rhinocerebral-mucormycosis-in-a-pediatric-patient-with-relapsed-pre-b-acute-lymphoblastic-leukemia
#12
Zephyr D Dworsky, John S Bradley, Matthew T Brigger, Alice L Pong, Dennis John Kuo
A 17-year-old female developed invasive rhinocerebral mucormycosis during intensive re-induction chemotherapy for relapsed pre-B acute lymphoblastic leukemia. Due to the high case fatality rate for invasive mucormycosis in profoundly immunosuppressed patients, an aggressive treatment regimen was pursued. In addition to the standard of care treatments with intravenous amphotericin and aggressive surgical debridements, she received intraventricular amphotericin to the brain via an Ommaya reservoir, hyperbaric oxygen treatments, filgrastim, intravenous immunoglobulin and anti-fungal in vitro synergy testing to allow for more targeted antifungal therapy with the addition of micafungin...
November 16, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29189509/successful-treatment-of-a-very-late-isolated-relapse-in-an-adolescent-with-a-picalm-mllt10-positive-t-lineage-acute-lymphoblastic-leukemia
#13
Emanuela Cannata, Piera Samperi, Carla Cimino, Silvia Marino, Federica Sullo, Elena Mirabile, Andrea Di Cataldo, Giovanna Russo, Luca Lo Nigro
T-lineage ALL is an aggressive disease that needs to be treated with intensive treatment schedules. A late relapse rarely occurs and a clear choice for second-line treatment is on debate. We report on a young adult with a very late isolated extramedullary relapse of PICALM-MLLT10 positive T-ALL, successfully treated with a chemotherapy-based and radiotherapy-based pediatric protocol. We demonstrate that relapse can occur in T-ALL although a SR-MRD behavior treated with a high-risk protocol; specific molecular diagnostic aberrations, as PICALM-MLLT10, are still conserved at very late relapse; a second-line treatment based on pediatric protocol can be effective...
November 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29178361/outcome-of-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia-after-blinatumomab-failure-no-change-in-the-level-of-cd19-expression
#14
Elias Jabbour, Johannes Düll, Musa Yilmaz, Joseph D Khoury, Farhad Ravandi, Nitin Jain, Hermann Einsele, Guillermo Garcia-Manero, Marina Konopleva, Nicholas J Short, Philip A Thompson, William Wierda, Naval Daver, Jorge Cortes, Susan O'Brien, Hagop Kantarjian, Max S Topp
Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has shown significant activity in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). Despite this improvement, most patients relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing after initial response. After a median follow-up of 49 months, 9 (13%) patients remained alive. The median overall survival after blinatumomab failure was 5...
November 27, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29174416/unrelated-donor-umbilical-cord-blood-transplant-versus-unrelated-hematopoietic-stem-cell-transplant-in-patients-with-acute-leukemia-a-meta-analysis-and-systematic-review
#15
REVIEW
Xiao Lou, Chuanhua Zhao, Hu Chen
Acute leukemia is a global disease with a poor prognosis for many patients. While an increasing number of patients with acute leukemia are being treated with unrelated hematopoietic stem cell transplants (HSCT) or umbilical cord blood transplants (UCBT), recent comparative reports of these 2 procedures are lacking. Therefore, we conducted a meta-analysis of the safety and efficacy of unrelated HSCT and unrelated single-unit UCBT for the treatment of pediatric and adult patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML)...
November 15, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29170254/wt1-loss-attenuates-the-tp53-induced-dna-damage-response-in-t-cell-acute-lymphoblastic-leukemia
#16
Fulvio Bordin, Erich Piovan, Elena Masiero, Alberto Ambesi-Impiombato, Sonia Minuzzo, Roberta Bertorelle, Valeria Sacchetto, Giorgia Pilotto, Giuseppe Basso, Paola Zanovello, Alberto Amadori, Valeria Tosello
Loss of function mutations and deletions in Wilms tumor 1 (WT1) gene are present in about 10% of T-cell acute lymphoblastic leukemia. Clinically, (WT1) mutations are enriched in relapsed series and are associated to inferior relapse-free survival in thymic T-cell acute lymphoblastic leukemia cases. Here, we demonstrate that WT1 plays a critical role in DNA damage response in T-cell leukemia. (WT1) loss conferred resistance to DNA damaging agents and attenuated the transcriptional activation of important apoptotic regulators downstream of TP53 in TP53-competent MOLT4 T-leukemia cells but not in TP53-mutant T-cell acute lymphoblastic leukemia cell lines...
November 23, 2017: Haematologica
https://www.readbyqxmd.com/read/29168171/the-arginine-metabolome-in-acute-lymphoblastic-leukemia-can-be-targeted-by-the-peg-recombinant-arginase-i-bct-100
#17
Carmela De Santo, Sarah Booth, Ashley Vardon, Antony Cousins, Vanessa Tubb, Tracey Perry, Boris Noyvert, Andrew Beggs, Margaret Ng, Christina Halsey, Pamela Kearns, Paul Cheng, Francis Mussai
Arginine is a semi-essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT-100, a pegylated recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute Lymphoblastic Leukemia is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT-100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone...
November 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29167392/tcr-engagement-negatively-affects-cd8-but-not-cd4-car-t-cell-expansion-and-leukemic-clearance
#18
Yinmeng Yang, M Eric Kohler, Christopher D Chien, Christopher T Sauter, Elad Jacoby, Chunhua Yan, Ying Hu, Kelsey Wanhainen, Haiying Qin, Terry J Fry
Chimeric antigen receptor (CAR)-expressing T cells induce durable remissions in patients with relapsed/refractory B cell malignancies. CARs are synthetic constructs that, when introduced into mature T cells, confer a second, non-major histocompatibility complex-restricted specificity in addition to the endogenous T cell receptor (TCR). The implications of TCR activation on CAR T cell efficacy has not been well defined. Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T cell therapy for pre-B cell acute lymphoblastic leukemia in which the CAR is introduced into T cells with known TCR specificity, we demonstrate loss of CD8 CAR T cell efficacy associated with T cell exhaustion and apoptosis when TCR antigen is present...
November 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29164065/transcriptional-and-microenvironmental-regulation-of-lineage-ambiguity-in-leukemia
#19
REVIEW
Tianyuan Hu, Rebecca Murdaugh, Daisuke Nakada
Leukemia is characterized by the uncontrolled production of leukemic cells and impaired normal hematopoiesis. Although the combination of chemotherapies and hematopoietic stem cell transplantation has significantly improved the outcome of leukemia patients, a proportion of patients still suffer from relapse after treatment. Upon relapse, a phenomenon termed "lineage switch" is observed in a subset of leukemia patients, in which conversion of lymphoblastic leukemia to myeloid leukemia or vice versa is observed...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#20
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
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