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Modern therapy of acute lymphoblastic leukemia

Pavel Klener, Tomas Etrych, Pavel Klener
Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short...
October 6, 2017: Current Medicinal Chemistry
Riad El Fakih, Elias Jabbour, Farhad Ravandi, Mona Hassanein, Farhan Anjum, Syed Ahmed, Hagop Kantarjian
Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) is a biologically, clinically, and genetically distinct subtype of precursor-B ALL. The Ph chromosome, results from a reciprocal translocation of the ABL1 kinase gene on chromosome 9 to the breakpoint cluster region (BCR) gene on chromosome 22. Depending on the translocation breakpoint, typically a p210 BCR-ABL1 or a p190 BCR-ABL onc protein are generated; both are constitutively active tyrosine kinases that play a central role to alter signaling pathways of cell proliferation, survival, and self-renewal, leading to leukemogenesis...
February 2018: American Journal of Hematology
Van Thu Huynh, Sharon Bergeron
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a common cancer in children, and outcomes have greatly improved because of the refinement of multiagent chemotherapy regimens that include intensified asparaginase therapy. Asparaginase, a cornerstone of modern pediatric chemotherapy regimens for ALL and asparaginase-containing protocols, is increasingly used in adolescent and adult patients historically treated with asparaginase-free regimens. 
. OBJECTIVES: This article is an overview of commonly encountered asparaginase-
associated toxicities and offers recommendations for treatment management...
October 1, 2017: Clinical Journal of Oncology Nursing
Renato Bassan, Tamara Intermesoli, Annamaria Scattolin, Piera Viero, Elena Maino, Rosaria Sancetta, Francesca Carobolante, Francesca Gianni, Paola Stefanoni, Manuela Tosi, Orietta Spinelli, Alessandro Rambaldi
The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
Joanna Pierro, Laura E Hogan, Teena Bhatla, William L Carroll
The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Likewise, early experiences with new immunotherapeutic approaches have shown great promise...
August 2017: Expert Review of Anticancer Therapy
Irappa Madabhavi, Apurva Patel, Malay Sarkar, Asha Anand, Harsha Panchal, Sonia Parikh
BACKGROUND: Effective and reliable venous access is one of the cornerstones of modern medical therapy in oncology. MATERIALS AND METHODS: This is a prospective observational study, which collected data of patients who require "PORT" catheter insertion for any cancer, at a tertiary care oncology hospital in Ahmadabad, Gujarat, India, during a 2-year period. AIMS AND OBJECTIVES: The main objective of this study was to study the various complications and outcomes related to "PORT" catheters...
2017: Clinical Medicine Insights. Oncology
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
Thai Hoa Tran, Mignon L Loh
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a newly identified high-risk (HR) B-lineage ALL subtype, accounting for ∼15% of children with National Cancer Institute-defined HR B-ALL. It occurs more frequently in adolescents and adults, having been reported in as much as 27% of young adults with ALL between 21 and 39 years of age. It exhibits adverse clinical features, confers a poor prognosis, and harbors a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, making it amenable to treatment with tyrosine kinase inhibitor (TKI) therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
Betül Orhan, Barış Malbora, Sezin Akça Bayar, Zekai Avcı, Bülent Alioğlu, Namık Özbek
OBJECTIVES: Ophthalmologic disease in patients with acute leukemia occurs due to primary leukemic infiltration (involvement), or secondary to the disease and its treatment. In recent years the life expectancy of acute leukemia patients has increased with the advent of modern therapies. The present study aimed to determine the incidence of ocular manifestations in children with acute leukemia. MATERIALS AND METHODS: The study included 120 patients diagnosed with acute leukemia at Başkent University Hospital, Pediatric Hematology Department between 1995 and 2010...
April 2016: Turkish Journal of Ophthalmology
K H Wu, H P Wu, H J Lin, C H Wang, H Y Chen, T Weng, C T Peng, Y H Chao
Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse...
August 2016: Current Oncology
Andra-Sorina Tatar, Timea Nagy-Simon, Ciprian Tomuleasa, Sanda Boca, Simion Astilean
Acute lymphoblastic leukemia (ALL) is the malignancy with the highest incidence amongst children (26% of all cancer cases), being surpassed only by the cancers of the brain and of the nervous system. The most recent research on ALL is focusing on new molecular therapies, like targeting specific biological structures in key points in the cell cycle, or using selective inhibitors for transmembranary proteins involved in cell signalling, and even aiming cell surface receptors with specifically designed antibodies for active targeting...
September 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Joe Antony Jacob, Jumah Masoud Mohammad Salmani, Baoan Chen
Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration...
2016: Patient Preference and Adherence
Jennifer J Wilkes, Sean Hennessy, Rui Xiao, Susan Rheingold, Alix E Seif, Yuan-Shung Huang, Neika Vendetti, Yimei Li, Rochelle Bagatell, Richard Aplenc, Brian T Fisher
BACKGROUND: There are few contemporary studies of volume-outcome relationships in pediatric oncology. Children with acute lymphoblastic leukemia (ALL) are treated at a wide variety of hospitals. We investigated if inpatient hospital volume influences outcomes. The objective of this study was to evaluate the relationship between inpatient pediatric and pediatric oncology volume and mortality and intensive care resources (ICU care). We hypothesized an inverse relationship between volume and these outcomes...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
Sahaja Acharya, Samantha Hsieh, Eric T Shinohara, Todd DeWees, Haydar Frangoul, Stephanie M Perkins
With modern therapy, overall survival (OS) for children with acute lymphoblastic leukemia approaches 90%. However, inferior outcomes for minority children have been reported. Data on the effects of ethnicity/race as it relates to socioeconomic status are limited. Using state cancer registry data from Texas and Florida, we evaluated the impact of neighborhood-level poverty rate and race/ethnicity on OS for 4719 children with acute lymphoblastic leukemia. On multivariable analysis, patients residing in neighborhoods with the highest poverty rate had a 1...
July 2016: Journal of Pediatric Hematology/oncology
E V Roitman, I M Kolesnikova, I L Davydkin, N S Kozlova, S A Roumiantsev
INTRODUCTION: In today's antithrombotic prevention we forget that hemorheologic abnormalities are part of Virchow's triad. Isn't this one of reasons that venous thromboembolism (VTE) including catheter-related thrombosis (CRT) retain high frequency despite of modern antithrombotic therapy? AIM: The aim was to investigate rheological behavior of blood in patients with some myeloproliferative neoplasms. MATERIALS AND METHODS: The study included 16 adults with Polycythemia Vera (PV), 42 young with acute lymphoblastic leukemia (ALL), and 67 healthy donors as control group...
April 2016: Thrombosis Research
Ümit Yavuz Malkan, Gürsel Güneş, Hakan Göker, İbrahim C Haznedaroğlu, Kadir Acar, Eylem Eliaçık, Sezgin Etgül, Tuncay Aslan, Seda Balaban, Haluk Demiroğlu, Osman I Özcebe, Nilgün Sayınalp, Salih Aksu, Yahya Büyükaşık
OBJECTIVE: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions...
December 1, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Magnus Borssén, Zahra Haider, Mattias Landfors, Ulrika Norén-Nyström, Kjeld Schmiegelow, Ann E Åsberg, Jukka Kanerva, Hans O Madsen, Hanne Marquart, Mats Heyman, Magnus Hultdin, Göran Roos, Erik Forestier, Sofie Degerman
BACKGROUND: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL...
July 2016: Pediatric Blood & Cancer
Renato Bassan, Elena Maino, Sergio Cortelazzo
Lymphoblastic lymphoma is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia, with no or limited bone marrow involvement (<25%), that develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum, and whose diagnostic hallmark is the expression of a T-/B-precursor cell immunophenotype, the T-cell subset accounting for 90% of all cases. The adoption of pediatric-derived, intensive lymphoblastic leukemia-like protocols led to significantly improved results, with survival rates of about 70% and 90% in adults and children, respectively...
May 2016: European Journal of Haematology
Anandani Nellan, Daniel W Lee
PURPOSE OF REVIEW: Modern immunotherapies, most notably in the form of anti-CD19 chimeric antigen receptor (CAR) T cells, have produced significant clinical responses in otherwise refractory pre-B-cell acute lymphoblastic leukemia patients. Several groups have simultaneously reported robust response rates in children and adults alike. These early studies indicate an impending shift in paradigm for the treatment of acute lymphoblastic leukemia. Incorporating CD19 CAR T-cell therapy into upfront or salvage regimens has its challenges and opportunities...
November 2015: Current Opinion in Hematology
E Eigendorff, A Hochhaus
BACKGROUND: The prognosis of adult patients with acute leukemia has continuously improved over the years due to the introduction of new diagnostic and therapeutic procedures and progress in the field of supportive therapy. METHODS: This article gives an overview of the currently available options and the clinical approach to the diagnostics and therapy of acute leukemia. RESULTS: The standardization as well as improvements in diagnostic procedures, in particular by immunocytological and genetic procedures, allow a more rapid determination of the exact diagnosis...
September 2015: Der Pathologe
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