308,956 results match your criteria Leukemias


Is DNA a better assay for residual disease in chronic myeloid leukemia?

Authors:
Jerald Radich

Haematologica 2018 Dec 30;103(12):1942-1944. Epub 2018 Nov 30.

Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

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http://dx.doi.org/10.3324/haematol.2018.205583DOI Listing
December 2018

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group.

Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Clinical Hematology, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.

Background: Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). Read More

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http://dx.doi.org/10.1002/cncr.32156DOI Listing

Preclinical activity of the antibody-drug conjugate denintuzumab mafodotin (SGN-CD19A) against pediatric acute lymphoblastic leukemia xenografts.

Pediatr Blood Cancer 2019 Apr 23:e27765. Epub 2019 Apr 23.

Children's Cancer Institute, School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.

Background: Denintuzumab mafodotin (SGN-CD19A) is a CD19-targeting antibody-drug conjugate, comprising a monoclonal antibody conjugated to the potent cytotoxin monomethyl auristatin F. Since denintuzumab mafodotin has previously shown activity against B-cell malignancies in early-stage clinical trials, it was of interest to test it against the Pediatric Preclinical Testing Program preclinical models of CD19 pediatric acute lymphoblastic leukemia (ALL).

Procedures: Denintuzumab mafodotin was evaluated against eight B-cell lineage ALL patient-derived xenografts (PDXs), representing B-cell precursor ALL, Ph-like ALL, and mixed-lineage leukemia rearranged infant ALL . Read More

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http://dx.doi.org/10.1002/pbc.27765DOI Listing

Reply to Letter to the Editor "Staging of acute leukemia based on central nervous system involvement alone: Is it appropriate?"

Pediatr Blood Cancer 2019 Apr 23:e27756. Epub 2019 Apr 23.

Cancer Council Queensland, Brisbane, Australia.

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http://dx.doi.org/10.1002/pbc.27756DOI Listing

Patient with mixed-phenotype acute leukemia with CBFB rearrangement.

Leuk Lymphoma 2019 Apr 23:1-3. Epub 2019 Apr 23.

a Departement of Leukemia , University of Texas MD Anderson Cancer Center , Houston , TX , USA.

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http://dx.doi.org/10.1080/10428194.2019.1605069DOI Listing

Low-dose azacitidine for relapse prevention after allogeneic hematopoietic cell transplantation in children with myeloid malignancies.

Pediatr Transplant 2019 Apr 23:e13423. Epub 2019 Apr 23.

Seattle Children's Hospital, University of Washington, Seattle, Washington.

Background: The prognosis of children who relapse after allogeneic hematopoietic cell transplant (alloHCT) for myeloid malignancies remains poor.

Procedure: To describe the safety and feasibility of post-transplant azacitidine for relapse prevention, we retrospectively reviewed the charts of 18 children undergoing alloHCT for myeloid malignancies.

Results: There were 15 evaluable patients since three patients did not receive planned azacitidine due to early relapse or TRM. Read More

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http://dx.doi.org/10.1111/petr.13423DOI Listing

Venous thromboembolism in a large cohort of children with acute lymphoblastic leukemia: Risk factors and effect on prognosis.

Res Pract Thromb Haemost 2019 Apr 27;3(2):234-241. Epub 2019 Feb 27.

Department of Pediatric Oncology/Hematology Erasmus MC-Sophia Children's Hospital Rotterdam the Netherlands.

Background: Venous thromboembolism (VTE) is relatively common in children with acute lymphoblastic leukemia (ALL). Thrombotic risk factors in ALL are asparaginase and steroids. However, within the ALL populations treated on the same regimen, it is less clear which other risk factors play a role. Read More

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http://dx.doi.org/10.1002/rth2.12182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462738PMC

Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow.

Mol Ther Oncolytics 2019 Sep 23;14:38-56. Epub 2019 Mar 23.

Human Antibody Lab, Innovation Center, Pasteur Institute of Iran, Tehran, Iran.

Despite the success of monoclonal antibodies (mAbs) to treat some disorders, the monospecific molecular entity of mAbs as well as the presence of multiple factors and pathways involved in the pathogenesis of disorders, such as various malignancies, infectious diseases, and autoimmune disorders, and resistance to therapy have restricted the therapeutic efficacy of mAbs in clinical use. Bispecific antibodies (bsAbs), by concurrently recognizing two targets, can partly circumvent these problems. Serial killing of tumor cells by bsAb-redirected T cells, simultaneous blocking of two antigens involved in the HIV-1 infection, and concurrent targeting of the activating and inhibitory receptors on B cells to modulate autoimmunity are part of the capabilities of bsAbs. Read More

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http://dx.doi.org/10.1016/j.omto.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463744PMC
September 2019

Fludarabine as an Adjuvant Improves Newcastle Disease Virus-Mediated Antitumor Immunity in Hepatocellular Carcinoma.

Mol Ther Oncolytics 2019 Jun 27;13:22-34. Epub 2019 Mar 27.

Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.

In addition to direct oncolysis, oncolytic viruses (OVs) also induce antitumor immunity, also called viro-immunotherapy. Limited viral replication and immune-negative feedback are the major hurdles to effective viro-immunotherapy. In this study, we found that use of an adjuvant of fludarabine, a chemotherapeutic drug for chronic myeloid leukemia, increased the replication of Newcastle disease virus (NDV) by targeting signal transducer and activator of transcription 1 (STAT1), which led to enhanced oncolysis of hepatocellular carcinoma (HCC) cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23727705193003
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http://dx.doi.org/10.1016/j.omto.2019.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461577PMC
June 2019
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Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Biomark Res 2019 11;7. Epub 2019 Apr 11.

1Department of Medicine, New York Medical College and Westchester Medical Center, Valhalla, NY 10595 USA.

B cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) frequently express CD19, CD20 and CD22 on the cell surfaces. Immunotherapeutic agents including antibodies and chimeric antigen receptor T cells are widely studied in clinical trials. Several antibody-drug conjugates (ADC) have been approved for clinical use (gemtuzumab ozogamicin in acute myeloid leukemia and brentuximab vedotin in Hodgkin lymphoma as well as CD30+ anaplastic large cell lymphoma). Read More

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http://dx.doi.org/10.1186/s40364-019-0160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458768PMC

IGF1R as druggable target mediating PI3K-δ inhibitor resistance in a murine model of chronic lymphocytic leukemia.

Blood 2019 Apr 22. Epub 2019 Apr 22.

Department of Internal Medicine III, University of Ulm, Germany

Targeted therapy is currently revolutionizing the treatment of cancers, but resistance evolves against these therapies and derogates their success. The PI3K-δ inhibitor idelalisib has been approved for CLL and NHL treatment, but the mechanisms conferring resistance in a subset of patients are unknown. Here, we modelled resistance to PI3K-δ inhibitor using a serial tumor transfer and treatment scheme in mice. Read More

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http://dx.doi.org/10.1182/blood.2018881029DOI Listing

The mitoNEET ligand NL-1 mediates anti-leukemic activity in drug resistant B-cell acute lymphoblastic leukemia.

J Pharmacol Exp Ther 2019 Apr 22. Epub 2019 Apr 22.

West Virginia University

Disease relapse in B-cell acute lymphoblastic leukemia (ALL), either due to development of acquired resistance after therapy or because of de novo resistance, remains a therapeutic challenge. In the present study, we have developed a cytarabine (Ara-C) resistant REH cell line (REH/Ara-C) as a chemoresistance model. REH/Ara-C (a) was not cross-resistant to vincristine or methotrexate; (b) showed a similar proliferation rate and cell surface marker expression as parental REH; (c) demonstrated decreased chemotaxis towards bone marrow stromal cells (BMSC); and (iv) expressed higher transcript levels of cytidine deaminase (CDA) and mitoNEET (CISD1) than the parental REH cell line. Read More

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http://dx.doi.org/10.1124/jpet.118.255984DOI Listing

2-D08 as a SUMOylation inhibitor induced ROS accumulation mediates apoptosis of acute myeloid leukemia cells possibly through the deSUMOylation of NOX2.

Biochem Biophys Res Commun 2019 Apr 19. Epub 2019 Apr 19.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic malignancy with poor survival and frequent relapse. Recently, a posttranslational modification of proteins with small ubiquitin-like modifiers (SUMO) has been notably implicated in a wide spectrum of diseases, especially cancers. Ubc9, as the sole E2-conjugating enzyme in SUMOylation cascade, particularly has been associated with adverse clinical outcomes. Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.04.079DOI Listing

Mechanisms of extramedullary relapse in acute lymphoblastic leukemia: Reconciling biological concepts and clinical issues.

Blood Rev 2019 Apr 17. Epub 2019 Apr 17.

CNRS, IGDR (Institut de Génétique et Développement de Rennes), Univ Rennes, UMR 6290, Rennes F-35000, France; Pediatric Hematology Department, University Hospital, Rennes, France. Electronic address:

Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) are currently above 85% due to huge improvements in treatment. However, 15-20% of children still experience relapses. Relapses can either occur in the bone marrow or at extramedullary sites, such as gonads or the central nervous system (CNS), formerly referred to as ALL-blast sanctuaries. Read More

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http://dx.doi.org/10.1016/j.blre.2019.04.003DOI Listing

Acquired Glanzmann thrombasthenia: From antibodies to anti-platelet drugs.

Authors:
Alan T Nurden

Blood Rev 2019 Mar 20. Epub 2019 Mar 20.

Institut de Rhythmologie et de Modélisation Cardiaque, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France. Electronic address:

In contrast to the inherited platelet disorder given by mutations in the ITGA2B and ITGB3 genes, mucocutaneous bleeding from a spontaneous inhibition of normally expressed αIIbβ3 characterizes acquired Glanzmann thrombasthenia (GT). Classically, it is associated with autoantibodies or paraproteins that block platelet aggregation without causing a fall in platelet count. However, inhibitory antibodies to αIIbβ3 are widely associated with primary immune thrombocytopenia (ITP), occur in secondary ITP associated with leukemia and related disorders, solid cancers and myeloma, other autoimmune diseases, following organ transplantation while cytoplasmic dysregulation of αIIbβ3 function features in myeloproliferative and myelodysplastic syndromes. Read More

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http://dx.doi.org/10.1016/j.blre.2019.03.004DOI Listing

Concurrent Squamous Cell Carcinoma and Chronic Lymphocytic Leukemia Presenting as an Enlarging Neck Mass.

J Investig Med High Impact Case Rep 2019 Jan-Dec;7:2324709619842904

1 University of Florida Jacksonville, FL, USA.

Chronic lymphocytic leukemia (CLL) patients are at an increased risk for developing more aggressive lymphomas via Richter's transformation and of developing secondary malignancies. Despite the known association for secondary cancers, oropharyngeal cancers occur rarely. We present a case of a woman with a history of CLL who presented to our facility via transfer for impending airway compromise. Read More

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http://dx.doi.org/10.1177/2324709619842904DOI Listing

The Antioxidant from Ethanolic Extract of Fruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect.

Int J Mol Sci 2019 Apr 19;20(8). Epub 2019 Apr 19.

Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan.

Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of fruits (RCE) along with its underlying mechanism of action. Read More

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http://dx.doi.org/10.3390/ijms20081935DOI Listing

Providing Informed Consent: A Standardized Case.

MedEdPORTAL 2016 Jul 21;12:10427. Epub 2016 Jul 21.

Director of Advancing Scholarship, University of Michigan Medical School.

Introduction: From the first day of residency, residents may be required to consent patients for interventions, procedures, or tests. The ability to perform an informed consent is considered one of the Association of American Medical College's Core Entrustable Professional Activities for entering residency. This case provides learners with the opportunity to obtain informed consent for a lumbar puncture procedure and to receive immediate structured feedback on their performance. Read More

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http://dx.doi.org/10.15766/mep_2374-8265.10427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464558PMC

Speciation analysis of arsenic in urine samples from APL patients treated with single agent AsO by HPLC-HG-AFS.

J Pharm Biomed Anal 2019 Apr 8;171:212-217. Epub 2019 Apr 8.

Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address:

Arsenic trioxide [AsO, arsenite (As) in solution] has been applied successfully for the treatment of acute promyelocytic leukemia (APL). The arsenic speciation analysis of urine is critical to reveal the metabolic mechanism and the relationship between arsenic species and the clinical response. To characterize the arsenic species in urine, a simple and robust HPLC-HG-AFS method was developed and validated to quantify the levels of arsenic species [As and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenate (As)] in urine samples from 66 patients with APL. Read More

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http://dx.doi.org/10.1016/j.jpba.2019.04.014DOI Listing

Sequential azacitidine and lenalidomide for patients with relapsed and refractory acute myeloid leukemia: Clinical results and predictive modeling using computational analysis.

Leuk Res 2019 Apr 13;81:43-49. Epub 2019 Apr 13.

University of Colorado Division of Hematology, Aurora, CO, United States. Electronic address:

Background: Patients with relapsed and refractory (R/R) acute myeloid leukemia (AML) have limited treatment options. Genomically-defined personalized therapies are only applicable for a minority of patients. Therapies without identifiable targets can be effective but patient selection is challenging. Read More

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http://dx.doi.org/10.1016/j.leukres.2019.04.005DOI Listing

Nucleophosmin in leukemia: consequences of anchor loss.

Int J Biochem Cell Biol 2019 Apr 19. Epub 2019 Apr 19.

Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic. Electronic address:

Nucleophosmin (NPM), one of the most abundant nucleolar proteins, has crucial functions in ribosome biogenesis, cell cycle control, and DNA-damage repair. In human cells, NPM occurs mainly in oligomers. It functions as a chaperone, undergoes numerous interactions and forms part of many protein complexes. Read More

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http://dx.doi.org/10.1016/j.biocel.2019.04.007DOI Listing

Sorafenib therapy is associated with improved outcomes for FLT3-ITD AML relapsing after allo-HSCT.

Biol Blood Marrow Transplant 2019 Apr 19. Epub 2019 Apr 19.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou, 510515, China. Electronic address:

The optimal therapy for acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this study, we retrospectively evaluated the efficacy of sorafenib combined with other therapeutic strategies as salvage therapy for these patients. A total of 83 AML with FLT3-ITD relapsing after allo-HSCT were enrolled in this study. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.04.018DOI Listing

Cytokines secreted from bone marrow derived mesenchymal stem cells promote apoptosis and change cell cycle distribution of K562 cell line as clinical agent in cell transplantation.

PLoS One 2019 22;14(4):e0215678. Epub 2019 Apr 22.

Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Mesenchymal stem cells (MSCs) are of special interest due their potential clinical use in cell-based therapy. Therapies engaging MSCs are showing increasing promise in the cancer treatment and anticancer drug screening applications. A multitude of growth factors and cytokines secreted from these cells are known to give such multifunctional properties, but details of their role are yet to be absolutely demonstrated. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215678PLOS
April 2019
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Evaluation of medication adherence and pharmacokinetics of dasatinib for earlier molecular response in Japanese patients with newly diagnosed chronic myeloid leukemia: a pilot study.

Ther Drug Monit 2019 Apr 16. Epub 2019 Apr 16.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan.

Background: Tyrosine kinase inhibitors (TKIs) markedly improve the survival for patients with chronic myeloid leukemia (CML). However, a decrease in adherence leads to undesired therapeutic outcomes. In this study, the relationships among adherence, pharmacokinetics, response, and adverse effects for dasatinib treatment were prospectively investigated. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000639DOI Listing

Development and validation of a sensitive UHPLC-MS/MS-based method for the analysis of folylpolyglutamate synthetase enzymatic activity in peripheral blood mononuclear cells: application in rheumatoid arthritis and leukemia patients.

Ther Drug Monit 2019 Apr 16. Epub 2019 Apr 16.

Department of Clinical Chemistry, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands.

Background: Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs like methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. To date, assessment of FPGS catalytic activity relies on assays utilizing radioactive substrates which are labor-intensive and require relatively large numbers of cells. Here, we describe a non-radioactive, UHPLC-MS/MS-based method allowing sensitive and accurate measurements of FPGS activity in low cell numbers (i. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000638DOI Listing

An Atypical Chronic Ulcer Caused by Acute Myeloid Leukemia.

Wounds 2019 Apr;31(4):E25-E28

Department of Surgical Infections, University Medical Centre Ljubljana, Slovenia and Medical Faculty, University in Ljubljana, Slovenia.

Introduction: Atypical chronic wounds are challenging for clinicians because of their identification, diagnosis, and treatment. These wounds may reflect an underlying systemic or malignant disease; therefore, an accurate diagnosis and initiation of the appropriate treatment are necessary.

Case Report: A 68-year-old man presented with an atypical chronic ulcer on his left shin of 2 years' duration. Read More

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April 2019
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A Precocious Presentation of B-cell Acute Lymphoblastic Leukemia as Infiltrated Plaques on the Face.

Cureus 2019 Feb 5;11(2):e4021. Epub 2019 Feb 5.

Dermatology, University of California San Diego, San Diego, USA.

Leukemia cutis, or infiltration of leukemic cells into the skin, occurs rarely in B-cell acute lymphocytic leukemia (ALL). Herein, we have described a rare, precocious presentation of B-cell ALL presenting as indurated facial plaques in a 69-year-old man. Biopsy of the facial plaques revealed precursor B-cell leukemia/lymphoma in the skin and prompted urgent hematologic-oncologic evaluation. Read More

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http://dx.doi.org/10.7759/cureus.4021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453639PMC
February 2019

Treatment According to Molecular Profiling in Relapsed/Refractory Cancer Patients: A Review Focusing on Latest Profiling Studies.

Comput Struct Biotechnol J 2019 26;17:447-453. Epub 2019 Mar 26.

Department of Haematology and Oncology, Medical University of Innsbruck, Austria.

In this review we aim to summarize studies investigating the impact of a molecular profiling (MP)-guided treatment approach in heavily pretreated cancer patients. In summary, many independent single- and multicenter studies showed a significant benefit of MP-guided treatment regarding response rates and survival. However, in the only randomized trial conducted so far, no benefit of MP-guided targeted therapy was observed. Read More

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http://dx.doi.org/10.1016/j.csbj.2019.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453774PMC

mutations and clonal dynamics.

Oncotarget 2019 Mar 12;10(21):2010-2011. Epub 2019 Mar 12.

Jaroslaw P. Maciejewski: Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Leukemia Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

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http://dx.doi.org/10.18632/oncotarget.26779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459340PMC

Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report.

Exp Ther Med 2019 May 26;17(5):4285-4288. Epub 2019 Mar 26.

Department of Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

As an essential component of consolidation and maintenance therapy for acute lymphoblastic leukemia (ALL), mercaptopurine (6-MP) causes critical myelosuppression. The current study aimed to clarify the reasons for severe myelosuppression and significant hyperpigmentationin a patient with ALL that received consolidation therapy. The present study performed patient NUDT15 testing with fluorescence hybridization and whole-exome sequencing. Read More

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http://www.spandidos-publications.com/10.3892/etm.2019.7434
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http://dx.doi.org/10.3892/etm.2019.7434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468867PMC
May 2019
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Coombs-positive refractory acquired thrombotic thrombocytopenic purpura in a patient with chronic myelomonocytic leukemia successfully treated with rituximab.

Acta Clin Belg 2019 Apr 22:1-5. Epub 2019 Apr 22.

b Intensive Care Unit, Department of Internal Medicine , University Hospital Centre Zagreb , Zagreb , Croatia.

Objectives: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare autoimmune disorder characterized by auto-antibodies to Willebrand factor (vWF) cleaving enzyme (ADAMTS13), resulting in unusually large vWF multimers that lead to platelet aggregation, microthrombi formation and microangiopathic hemolytic anemia. Hemolysis in aTTP is mechanical; thus, direct antiglobulin test (Coombs test) is usually negative. Multiple autoimmune conditions and various auto-antibodies have been described in the context of chronic myelomonocytic leukemia (CMML). Read More

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http://dx.doi.org/10.1080/17843286.2019.1608395DOI Listing

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects.

Xenobiotica 2019 Apr 22:1-60. Epub 2019 Apr 22.

a Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.

1. Asciminib is a potent, specific BCR-ABL1 inhibitor being developed for the treatment of patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL). 2. Read More

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https://www.tandfonline.com/doi/full/10.1080/00498254.2019.1
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http://dx.doi.org/10.1080/00498254.2019.1594449DOI Listing
April 2019
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Myeloid sarcoma presenting as bilateral acute otitis externa in newly diagnosed acute myeloid leukemia.

Int J Pediatr Otorhinolaryngol 2019 Apr 3;122:126-129. Epub 2019 Apr 3.

Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, OH, USA.

Myeloid sarcoma (MS) is an extramedullary collection of immature myeloid cells that can commonly occur with acute myeloid leukemia (AML). While head and neck presentations are not unheard of, there have been few published pediatric cases of external auditory canal MS. Here, we report a case of a 14-year-old male who presented with MS masquerading as bilateral acute otitis externa. Read More

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http://dx.doi.org/10.1016/j.ijporl.2019.04.002DOI Listing

Efficacy and tolerability of mitoxantrone for neuromyelitis optica spectrum disorder: A systematic review.

J Neuroimmunol 2019 Apr 15;332:126-134. Epub 2019 Apr 15.

Department of Neurosciences, University of the Philippines Manila-Philippine General Hospital, Philippines.

The review assessed the efficacy and tolerability of mitoxantrone in patients with neuromyelitis optica spectrum disorder (NMOSD). Eight articles were reviewed with a total of 117 patients. Annualized relapse rate and progression of disability dramatically decreased post-treatment in most studies. Read More

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http://dx.doi.org/10.1016/j.jneuroim.2019.04.007DOI Listing

Ofatumumab is safe and effective as front-line treatment in older patients with chronic lymphocytic leukemia and severe co-morbidities, including other malignancies.

J Geriatr Oncol 2019 Apr 17. Epub 2019 Apr 17.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: The majority of patients with chronic lymphocytic leukemia (CLL) are older and have multiple comorbidities, including other cancer diagnoses. These patients are routinely excluded from participation in clinical trials.

Objective: In this phase II study, we determined the activity and toxicity of ofatumumab, a fully human anti-CD20 monoclonal antibody, in older patients with CLL, poor performance status and comorbidities. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S18794068193003
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http://dx.doi.org/10.1016/j.jgo.2019.04.002DOI Listing
April 2019
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Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden.

Biochem Pharmacol 2019 Apr 18. Epub 2019 Apr 18.

Division of Drug Research, Department of Medical and Health Sciences, Linköping University, SE-581 83 Linköping, Sweden. Electronic address:

Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.04.020DOI Listing

Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Mol Ther 2019 Apr 8. Epub 2019 Apr 8.

Allogene Therapeutics, Inc., 210 E. Grand Avenue, South San Francisco, CA 94080, USA. Electronic address:

Clinical success of autologous CD19-directed chimeric antigen receptor T cells (CAR Ts) in acute lymphoblastic leukemia and non-Hodgkin lymphoma suggests that CAR Ts may be a promising therapy for hematological malignancies, including multiple myeloma. However, autologous CAR T therapies have limitations that may impact clinical use, including lengthy vein-to-vein time and manufacturing constraints. Allogeneic CAR T (AlloCAR T) therapies may overcome these innate limitations of autologous CAR T therapies. Read More

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http://dx.doi.org/10.1016/j.ymthe.2019.04.001DOI Listing
April 2019
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Xylo-C-nucleosides with a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base: Synthesis and antiproliferative properties.

Bioorg Med Chem Lett 2019 Apr 15. Epub 2019 Apr 15.

Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49-box 1041, Leuven 3000, Belgium. Electronic address:

The synthesis of a xylo-C-nucleoside containing pyrrolo[2,1-f][1,2,4]triazin-4-amine as nucleobase along with that of its 1'-cyano analogue is described. Among different experimental conditions explored in order to optimize a key debenzylation step in the presented synthetic route, it was found that palladium catalyzed hydrogen transfer allowed for obtaining the target compounds in good yields. The resulting mixture of epimers was separated and each was characterized by NOESY NMR experiments. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.04.023DOI Listing

Eremothecium coryli bloodstream infection in a patient with acute myeloid leukemia: first case report of human infection.

Diagn Microbiol Infect Dis 2019 Mar 27. Epub 2019 Mar 27.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Eremothecium coryli is a dimorphic fungus of the Saccharomycetes class. While species within this class are known to cause human infection, Eremothecium species have previously only been known as phytopathogens and never been isolated from a human sample. Here, we report the first known case of human E. Read More

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http://dx.doi.org/10.1016/j.diagmicrobio.2019.03.011DOI Listing

Work-up for Fever During Neutropenia for Both the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient.

Infect Dis Clin North Am 2019 Jun;33(2):381-397

Division of Infectious Diseases, Vanderbilt University Medical Center, A2200 MCN, 1161 21st Avenue South, Nashville, TN 37232-2605, USA. Electronic address:

Fever is a common complication in patients with underlying neutropenia and is associated with significant mortality in neutropenic patients with acute myelogenous leukemia or hematopoietic cell transplant. Fever may be the only sign of infection and requires further clinical assessment, including a history, a physical examination, and additional laboratory and radiographic testing. National and international guidelines recommend initiation of empiric antimicrobial therapy in patients with fever during neutropenia. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08915520193000
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http://dx.doi.org/10.1016/j.idc.2019.02.003DOI Listing
June 2019
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Targeting non-oncogene ROS pathway by alantolactone in B cell acute lymphoblastic leukemia cells.

Life Sci 2019 Apr 17. Epub 2019 Apr 17.

Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China; Department of General Practice, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China. Electronic address:

Aims: Alantolactone (ALT) is active component of natural product Inula helenium with a lot of pharmacological effects, including anti-tumor effect. The present work aimed to explore the antitumor effect of ALT in B cell acute lymphoblastic leukemia (B-ALL).

Main Methods: B-ALL cells were treated with various concentrations of ALT, and then trypan blue assay, Annexin V/PI staining assay, PI staining assay, western blot analysis were employed to measure the effect of ALT on viability, apoptosis and cell cycle in B-ALL cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00243205193029
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http://dx.doi.org/10.1016/j.lfs.2019.04.034DOI Listing
April 2019
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Acute myeloid leukemia with t(8;21)(q22;q22.1)/RUNX1-RUNX1T1 and KIT Exon 8 mutation is associated with characteristic mastocytosis and dismal outcomes.

Exp Mol Pathol 2019 Apr 17. Epub 2019 Apr 17.

Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. Electronic address:

KIT mutations are observed in about 20-40% of acute myeloid leukemia with t(8;21)(q22;q22.1)/RUNX1-RUNX1T1 [abbreviated AML t(8;21) here] with mutations involving exon 17 being the most common. Despite high frequencies of KIT mutations in both AML t(8;21) and systemic mastocytosis (SM), AML t(8;21) associated with SM is uncommon, and restricted to KIT exon 17 mutated cases. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00144800193021
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http://dx.doi.org/10.1016/j.yexmp.2019.04.009DOI Listing
April 2019
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Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia.

Transpl Infect Dis 2019 Apr 20:e13096. Epub 2019 Apr 20.

Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taiwan.

Background: Owing to the shortage of hematopoietic stem cells from matched sibling donors (MSD) and matched unrelated donors (MUD), the number of patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) has rapidly increased. Despite a comparable overall survival (OS) and leukemia-free survival using this approach, some evidence suggests that haploidentical allo-HSCT recipients have a higher incidence of cytomegalovirus (CMV) infection, though this has not been clearly established.

Methods: This study retrospectively compared the cumulative incidence of CMV DNAemia, 2-year OS, and leukemia-free survival rates in acute leukemia patients with with MSD (n=41), MUD (n=18), and haploidentical donor allografts (n=21). Read More

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http://dx.doi.org/10.1111/tid.13096DOI Listing

Non-genotoxic MDM2 inhibition selectively induces pro-apoptotic p53 gene signature in chronic lymphocytic leukemia cells.

Haematologica 2019 Apr 19. Epub 2019 Apr 19.

Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK;

Chronic lymphocytic leukemia is a clinically heterogeneous haematological malignancy which is ~90% TP53 wild-type at diagnosis. As a primary repressor of p53, targeting of mouse double-minute-2 homolog (MDM2) is an attractive therapeutic approach for non-genotoxic reactivation of p53. Since discovery of the first MDM2 inhibitor, Nutlin-3a, newer potent and bioavailable compounds have been developed. Read More

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http://dx.doi.org/10.3324/haematol.2018.206631DOI Listing

Clonal haematopoiesis and risk of acute myeloid leukemia.

Haematologica 2019 Apr 19. Epub 2019 Apr 19.

Washington University School of Medicine;

Nearly all adults harbor acute myeloid leukemia-related clonal hematopoietic mutations at a variant allele fraction of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow-up, to investigate associations of clonal mutations of ≥0. Read More

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http://dx.doi.org/10.3324/haematol.2018.215269DOI Listing
April 2019
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Evolutionary trajectory of leukemic clones and its clinical implications.

Haematologica 2019 Apr 19. Epub 2019 Apr 19.

Weizamnn Institute of scirence

Acute Myeloid Leukemia's ontogeny is a multistep process. It is driven both by features of the malignant clone itself, as well as by environmental pressures, making it a unique process in each individual. Recent years' technological advancements have increased our understanding about the steps that take place at the genomic level. Read More

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http://dx.doi.org/10.3324/haematol.2018.195289DOI Listing