期刊
PEDIATRIC BLOOD & CANCER
卷 46, 期 1, 页码 18-25出版社
WILEY
DOI: 10.1002/pbc.20406
关键词
acute lymphoblastic leukaemia; asparaginase; asparagine; children; CSF
Background and Procedure. Pharmacological surrogate parameters are considered a useful tool in estimating the treatment intensity of asparaginase (ASNase) preparations. When a pegylated ASNase (single infusion of 2,500 IU/m(2) polyethylene glycol (PEG)-ASNase, Oncaspar (TM)) was introduced into the treatment protocols of the German Cooperative Acute Lymphoblastic Leukaemia (COALL) study group, this was accompanied by a drug monitoring programme measuring serum ASNase activity and asparagine (ASN) concentrations in the cerebrospinal fluid (CSF) in 70 children. Results. Four hundred fifty-nine serum samples from 67 evaluable patients showed medians of ASNase activity of 1,189.5, 824.5, 310.5, 41 and 4 U/l on day 7 +/- 1,14 1,21 1,28 1 and 35 1 respectively. One hundred eighty-four samples from 59 patients were evaluable for ASN concentrations in the CSF. The medians of ASN concentration were < 0.2, 0.2, 0.9 and 3.2 mu M on day 14 +/- 1, 21 +/- 1, 28 +/- 1 and 35 +/- 1 respectively. When relating CSF ASN levels to the serum ASNase activity measured on the same day, a median of 1.2 mu M CSF ASN was associated with values of serum ASNase activity between >= 2.5 and < 100 U/l. Serum ASNase activity values >= 100 U/l were associated with a median CSF ASN of < 0.2 mu M, with 13/27 samples being incompletely depleted. Conclusions. The treatment intensity achieved with PEG ASNase in the present study appears to be acceptable based on the surrogate of serum ASNase activity. However, the pharmacological objective of ASNase treatment, that is, complete CSF ASN depletion with an ASNase activity >100 U/l, was not ensured. Nevertheless, one must also be aware that the minimum ASN concentration required for leukaemic cell growth is yet to be established.
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