Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six patients with newly diagnosed ALL (age range 15-49 years, median 32 years) received treatment comprising: cycles 1 and 2: adriamycin 30 mg/m2 days 1-3, vincristine: 2 mg days 1, 8, and 15, with prednisolone 40 mg daily, given until complete remission (CR). L-asparaginase 10000 units/m2, days 1-14, was given only with the first cycle. Cycle 3 consisted of 100 mg/m2 etoposide orally, days 1-5, and 1 gm/m2 bd cytosine arabinoside (ara-C) days 1-5. Cycles 1-3 were then repeated. Intrathecal methotrexate (MTX) 12.5 mg was given on day 1 of each treatment cycle. The first 12 consecutive patients received this chemotherapy alone, the subsequent 14 received, in addition, 3 micrograms/kg GM-CSF subcutaneously, from day 4 of cycles 1,2,4 and 5 (and from day 6 of cycles 3 and 6) until the absolute neutrophil count had reached 0.5 x 10(9)/1. All patients in whom CR was achieved then received prophylactic cranial irradiation. With the exception of those with T-ALL, this was followed by oral maintenance therapy consisting of 6-mercaptopurine, MTX, and cyclophosphamide for 3 years. Patients receiving GM-CSF did not have shorter intercycle times or a lower incidence of documented infections than those who did not receive it. The CR rate was 89% overall-uninfluenced by GM-CSF, but higher than that achieved previously at St Bartholomew's Hospital in an equivalent age-group.
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PMID:Intensive chemotherapy for adult acute lymphoblastic leukaemia given with or without granulocyte-macrophage colony stimulating factor. 900 54

Therapeutic proteins in general induce an immune response, especially when administered as multiple doses over prolonged periods. Non-human therapeutic proteins such as asparaginase and streptokinase induce antibodies by the classical immune reaction and their primary immunogenic factor is the degree of non-self. Human therapeutic proteins such as the interferons and GM-CSF breakdown immune tolerance and protein aggregation is their main factor inducing antibodies. Many other factors influence the level of immunogenicity of proteins, such as storage conditions,contaminants or impurities in the preparation, downstream processing, dose and length of treatment, as well as route of administration, appropriate formulation and disease status and concomitant treatment of patients. Clinical manifestations of antibodies directed against the protein include loss of efficacy, cross neutralization of endogenous proteins and general immune system effects, such as anaphylaxis or serum sickness.
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PMID:How to predict and prevent the immunogenicity of therapeutic proteins. 1860 64