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refractory acute leukemia

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https://www.readbyqxmd.com/read/29222234/progress-in-adult-all-incorporation-of-new-agents-to-frontline-treatment
#1
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/29218851/clinical-experience-with-the-bcl2-inhibitor-venetoclax-in-combination-therapy-for-relapsed-and-refractory-acute-myeloid-leukemia-and-related-myeloid-malignancies
#2
Courtney D DiNardo, Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed...
December 8, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#3
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29214213/therapeutic-potential-of-arsenic-trioxide-ato-in-treatment-of-hepatocellular-carcinoma-role-of-oxidative-stress-in-ato-induced-apoptosis
#4
Erika B Dugo, Clement G Yedjou, Jacqueline J Stevens, Paul B Tchounwou
Hepatocellular carcinoma (HCC), the dominant form of primary liver cancer, is the sixth most common cancer in the world with more than 700,000 people diagnosed annually. Arsenic trioxide (ATO) has been shown to be a potent anticancer agent in various carcinomas, proving particularly effective in the clinical treatment of relapsed and refractory acute promyelocytic leukemia. However, its bioactivity and molecular mechanisms against HCC has not been fully studied. Using human HCC (HepG2) cells as a test model, we studied the effects of ATO and examined the role of oxidative stress (OS) and apoptosis in cytotoxicity...
2017: Annals of Clinical Pathology
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
#5
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/29211308/dose-schedule-safety-and-efficacy-of-guadecitabine-in-relapsed-or-refractory-acute-myeloid-leukemia
#6
Gail J Roboz, Hagop M Kantarjian, Karen W L Yee, Patricia L Kropf, Casey L O'Connell, Elizabeth A Griffiths, Wendy Stock, Naval G Daver, Elias Jabbour, Ellen K Ritchie, Katherine J Walsh, David Rizzieri, Scott D Lunin, Tania Curio, Woonbok Chung, Yong Hao, James N Lowder, Mohammad Azab, Jean-Pierre J Issa
BACKGROUND: Outcomes for patients with relapsed or refractory acute myeloid leukemia (AML) are poor. Guadecitabine, a next-generation hypomethylating agent, could be useful in treating such patients. METHODS: In this multicenter, open-label, phase 2 dose-expansion study, AML patients from 10 North American medical centers were first randomized (1:1) to receive subcutaneous guadecitabine at 60 or 90 mg/m2 on 5 consecutive days in each 28-day cycle (5-day regimen)...
December 6, 2017: Cancer
https://www.readbyqxmd.com/read/29209600/targeting-flt3-signaling-in-childhood-acute-myeloid-leukemia
#7
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/29200689/acute-lymphoblastic-leukemia-as-secondary-malignancy-in-a-case-of-ewing-s-sarcoma-on-treatment
#8
Satyam Satyarth, Sonia Parikh, Asha Anand, Jyoti Sawhney, Harsha Panchal, Apurva Patel, Sandeep Shah
The survival of Ewing's sarcoma (ES) has improved due to advances in both local and systemic therapy. This has given rise to an increased detection of second malignant neoplasms which can be in the form of solid tumors and hematological malignancies. The most common hematological malignancies are acute myeloid leukemia/myelodysplastic syndrome. Acute lymphoblastic leukemia (ALL) is relatively uncommon in occurrence in this setting. Furthermore, the average refractory period for hematological malignancies varies from 3 to 5 years...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29196926/glioblastoma-and-acute-myeloid-leukemia-malignancies-with-striking-similarities
#9
REVIEW
Eric Goethe, Bing Z Carter, Ganesh Rao, Naveen Pemmaraju
Acute myeloid leukemia (AML) and glioblastoma (GB) are two malignancies associated with high incidence of treatment refractoriness and generally, uniformly poor survival outcomes. While the former is a hematologic (i.e. a "liquid") malignancy and the latter a solid tumor, the two diseases share both clinical and biochemical characteristics. Both diseases exist predominantly in primary (de novo) forms, with only a small subset of each progressing from precursor disease states like the myelodysplastic syndromes or diffuse glioma...
December 1, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29196889/durable-resolution-of-severe-psoriasis-in-a-patient-treated-with-pentostatin-for-hairy-cell-leukemia-a-case-report
#10
Tamim Alsuliman, Kaiss Lassoued, Maifa Belghoul, Karima Debbache, Bachra Choufi
INTRODUCTION: Pentostatin (2'-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine) are adenosine analogues widely used to treat lymphoid malignancies, mainly hairy cell leukemia (HCL). Oral or parenteral adenosine analogues have been also used as immunomodulatory agents in multiple sclerosis and in acute graft-versus-host disease. CASE REPORT: Here, we report the case of a 43-year-old patient with a history of extensive psoriasis who later developed HCL. RESULTS: The patient had achieved complete remission of both psoriasis and HCL after receiving intravenous infusions of pentostatin...
December 1, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/29196412/a-phase-1-trial-of-vadastuximab-talirine-as-monotherapy-in-patients-with-cd33-positive-acute-myeloid-leukemia-aml
#11
Eytan M Stein, Roland B Walter, Harry P Erba, Amir T Fathi, Anjali S Advani, Jeffrey E Lancet, Farhad Ravandi, Tibor Kovacsovics, Daniel J DeAngelo, Dale Bixby, Stefan Faderl, Anand P Jillella, Phoenix Ho, Megan M O'Meara, Baiteng Zhao, Charles Biddle-Snead, Anthony S Stein
Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study (clinicaltrials.gov NCT01902329) evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naïve patients...
December 1, 2017: Blood
https://www.readbyqxmd.com/read/29190182/checkpoint-inhibition-in-pediatric-hematologic-malignancies
#12
Kara L Davis, Archana M Agarwal, Anupam R Verma
Immune surveillance comprising of adaptive and innate immune systems is naturally designed to eliminate cancer development; overexpression of inhibitory receptors and their ligands prevent this check and lead to evasion and hence cancer progression and metastasis. The use of tumor-specific monoclonal antibodies (MAbs) targeting these checkpoint regulators is promising and has led to this novel field of cancer immunotherapy. The first antibody directed against cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ipilimumab, showed promising results in clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29190169/tacl-ing-supportive-care-needs-in-pediatric-early-phase-clinical-trials-for-acute-leukemia-a-report-from-the-therapeutic-advances-in-childhood-leukemia-lymphoma-tacl-consortium-supportive-care-committee
#13
E Orgel, J J Auletta
A Supportive Care Committee was recently developed within the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Consortium. This was substantiated by the significantly high rate of serious adverse events (SAE) (CTCAE Grade ≥3 toxicity) experienced by patients with relapse/refractory acute leukemia enrolled on our phase I trials. Such treatment-related toxicity has resulted in patients being removed from study and thus potentially not receiving clinical benefit from the novel therapy. In addition, increased treatment-related toxicity may compromise new agents from moving forward in their clinical development...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29190164/investigating-the-biology-of-relapsed-acute-leukemia-proceedings-of-the-therapeutic-advances-for-childhood-leukemia-lymphoma-tacl-consortium-biology-working-group
#14
Deepa Bhojwani, Michael J Burke, Terzah Horton, David S Ziegler, Maria Luisa Sulis, Kirk R Schultz, Alan Wayne, Shai Izraeli, Bill H Chang
During the 2016 Therapeutic Advances for Childhood Leukemia & Lymphoma (TACL) Consortium investigators' meeting (Los Angeles, CA), a Biology Working Group was established to support the consortium's mission of developing innovative therapies for currently incurable childhood leukemias and lymphomas. The charge of the Biology Working Group was to address how TACL could advance biological investigations of pediatric relapsed/refractory hematologic malignancies while undertaking forward-looking therapeutic trials...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29181696/comparison-of-clinical-remission-and-survival-between-clag-and-flag-induction-chemotherapy-in-patients-with-refractory-or-relapsed-acute-myeloid-leukemia-a-prospective-cohort-study
#15
Y Bao, J Zhao, Z-Z Li
PURPOSE: To compare the clinical remission and survival between CLAG and FLAG induction chemotherapy in treating patients with refractory or relapsed acute myeloid leukemia (R/R AML). METHODS: 103 R/R AML patients were consecutively enrolled in this prospective cohort study. 55 patients were treated by CLAG induction chemotherapy as follows: 5 mg/m2/day cladribine (days 1-5); 2 g/m2/day cytarabine (days 1-5) and 300 μg/day filgrastim (days 0-5). While 48 patients were treated by FLAG: 30 mg/m2/day fludarabine (days 1-5), 2 g/m2/day cytarabine (days 1-5), and 300 μg/day filgrastim (days 0-5)...
November 27, 2017: Clinical & Translational 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
#16
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/29175379/ex-vivo-sensitivity-profiling-to-guide-clinical-decision-making-in-acute-myeloid-leukemia-a-pilot-study
#17
Ronan T Swords, Diana Azzam, Hassan Al-Ali, Ines Lohse, Claude-Henry Volmar, Justin M Watts, Aymee Perez, Ana Rodriguez, Fernando Vargas, Roy Elias, Francisco Vega, Arthur Zelent, Shaun P Brothers, Taher Abbasi, Jonathan Trent, Shaukat Rangwala, Yehuda Deutsch, Eibhlin Conneally, Leylah Drusbosky, Christopher R Cogle, Claes Wahlestedt
A precision medicine approach is appealing for use in AML due to ease of access to tumor samples and the significant variability in the patients' response to treatment. Attempts to establish a precision medicine platform for AML, however, have been unsuccessful, at least in part due to the use of small compound panels and having relatively slow turn over rates, which restricts the scope of treatment and delays its onset. For this pilot study, we evaluated a cohort of 12 patients with refractory AML using an ex vivo drug sensitivity testing (DST) platform...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29167924/persistent-cytarabine-and-daunorubicin-exposure-after-administration-of-novel-liposomal-formulation-cpx-351-population-pharmacokinetic-assessment
#18
Mina Nikanjam, Edmund V Capparelli, Jeffrey E Lancet, Arthur Louie, Gary Schiller
PURPOSE: CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML). The current study investigated the pharmacokinetics (PK) of this liposomal formulation. METHODS: CPX-351 PK data (cytarabine, daunorubicin, and metabolites) from a phase I study of relapsed and refractory AML were used for the analysis. Therapy was given days 1, 3, and 5 of induction (3-134 units/m(2))...
November 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29167392/tcr-engagement-negatively-affects-cd8-but-not-cd4-car-t-cell-expansion-and-leukemic-clearance
#19
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/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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