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Radiation Hormesis in Cancer
Published in T. D. Luckey, Radiation Hormesis, 2020
An extensive survey of cancer mortality near nuclear installations of England and Wales from 1959 to 1980 was summarized by Forman et al.287 This involved about 11,000 deaths each in exposed and control groups. “These data show conclusively that there has been no general increase in cancer mortality in the vicinity of nuclear installations in a 22-year period beginning several years after the opening of the installations that have released the largest amounts of radionuclides into the environment.”287 Of 13 positive correlations found, three concerned liver; excess liver cancer mortalities “…were all present before the opening of the installations as well as after”. Two excess mortalities involved lymphoid leukemia in young persons, 0 to 24 years old; this is not considered to be a radiation-induced cancer in older people. Since the control group had only 56% as much mortality from lymphoid leukemia as the general population, these data may be suspect. The study of brain cancer in the young group was quite squewed; “population selection bias” is the phrase used to discredit such data. In persons 25 to 74 years old, Hodgkin’s disease was excessive in two catagories; this elevated the catagory of “all lymphomas” to significant status, p = 0.04. Of the remaining four catagories, lung mortality accounted for about 3000 deaths in each group. However, the standard mortality ratio for lung cancer mortality in the control group was 90.3; this suggested a bias in the control group compared with the general population.
Logistic Regression for Binary Classification
Published in K. V. S. Sarma, R. Vishnu Vardhan, Multivariate Statistics Made Simple, 2018
K. V. S. Sarma, R. Vishnu Vardhan
9.4 A Study on classifying the status of Acute Lymphoid Leukemia (ALL) as ‘Alive’ or ‘Dead’ is carried out and a sample of 24 records with Age (in years), Sex (0=Female; 1= Male), Risk (1=High; 2=Standard), Duration of Symptoms (in weeks), Antibiotic Before Induction (1=Yes, 0=No), Platelets, Creatinine, Albumin and Outcome (1=Dead; 0=Alive) are given in the Table 9.4.
Case 58
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
The important phases of treatment are induction, pre-emptive central nervous system (CNS)-directed, intensification and maintenance. Induction is with a combination of vinca alkaloids, prednisolone, anthracyclines, cytarabine and l-asparaginase. All children with acute lymphoid leukaemia (ALL) are at risk of CNS disease and treatment aimed at preventing CNS disease should be offered in pre-symptomatic patients. Such treatment includes intrathecal chemotherapy and high-dose treatment with chemotherapeutic drugs that cross the blood–brain barrier (e.g. methotrexate, cytosine arabinoside). Risk stratification is applied to groups of patients, and this is based on prognostic categories and evaluation of response/assessment of minimal residual disease. The overall prognosis for childhood ALL is very good and more than 85% of patients are cured.
The future of antibody therapy in chronic lymphocytic leukemia
Published in Expert Opinion on Emerging Drugs, 2021
Jennifer L. Crombie, Jennifer R. Brown
Despite lower responses in initial studies, the role of rituximab was further explored for the treatment of SLL/CLL, focusing on higher or more intensive dosing[21]. Dose escalation studies demonstrated that rituximab could be administered safely, and response rates improved to 36% in relapsed refractory CLL and 60% in other subtypes of B-cell lymphoid leukemia[22]. Response was correlated with dose, with an overall response of 22% for patients treated at 500 to 825 mg/m2, 43% for those treated at 1,000 to 1,500 mg/m2, and 75% for those treated at the highest dose of 2,250 mg/m2 (P = .007)[22]. Alternative dosing schedules were also investigated with attempts to mitigate associated infusion reactions. A similar study demonstrated that rituximab could be safely administered three times per week with acceptable safety and improved efficacy[23].
Targeted therapy in acute myeloid leukemia: current status and new insights from a proteomic perspective
Published in Expert Review of Proteomics, 2020
Anneke D. van Dijk, Eveline S. J. M. de Bont, Steven M. Kornblau
In hematological diseases, significant improvement in outcomes has been shown with immunotherapy-based regimes. The first FDA approved antibody-based drug in cancer was rituximab, which targets the antigen CD20 on the surface of specific B-cell non-Hodgkin lymphoma (NHL) cells and is part of the gold standard ever since [16,17]. Moreover, in B-cell acute lymphoid leukemia (B-ALL), success has been booked with chimeric antigen receptor (CAR)-T-cell therapy. CAR-T-cells are genetically engineered patient cells that express CARs to target specific antigens on cancer cells. Tisagenlecleucel targeting the CD19 antigen was the first CAR-T cell drug that received FDA approval. In 2018, Maude et al. published their phase II study of Tisagenlecleucel in pediatric B-ALL that showed a complete remission rate of 81% [18]. The relapse rate, however, remained high, especially with antigen-negative leukemia [19]. The key to success in immunotherapy lies within the identification of a target antigen that is predominantly expressed on the surface of malignant cells, such as CD20 on B-cell NHL and CD19 on B-ALL cells. Expression of such target should preferably be restricted to malignant cells, and expression should be present on mature malignant cells as well as on malignant stem cells. For AML the identification of leukemia-specific antigens has been less successful and current therapeutic antibody and CAR-T approaches are directed against CD33 and CD123, both of which are also present on normal hematopoietic stem cells; thus caution in their usage is warranted [20].
Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China
Published in Journal of Medical Economics, 2019
Shaoyan Hu, Yi Han, Wenjie Zhang, Tianxiang Zhang, Xingxing Yao, Li Liu
Approved by the US Food and Drug Administration (FDA) in 2002, rasburicare is indicated for both pediatric and adult patients who are at risk of developing TLS or for the management of elevated uric acid levels. Rasburicase is a recombinant urate oxidase enzyme that can be administered to patients at risk of TLS to convert uric acid to a more soluble product, allantoin, which can be excreted by the kidneys more readily. Therefore, rasburicase is able to prevent or treat TLS in patients with malignancies. It has been widely used for both TLS prevention and treatment in developed countries. Economic studies showed that preventing and treating TLS with rasburicase are highly cost-effective in both pediatric and adult patients with hematological cancer2. Studying patients with acute myeloid/lymphoid leukemia (AML/ALL) and non-Hodgkin’s lymphoma (NHL), Annemans et al.2 found that prevention with rasburicase is cost-effective in children with incremental cost-effectiveness ratios (ICER) between €425 and €3,054 per life-year saved. In addition, treatment of established TLS with rasburicase has demonstrated cost savings among children and is highly cost-effective in adults2.