ABSTRACT
UNLABELLED: Polyethylene glycol conjugated asparaginase (PEG-ASNase) can be substituted in cases of hypersensitivity to native Escherichia coli asparaginase. We measured asparagine (asn) levels in plasma after a single dose of 2,500 IU/m(2) i.v. PEG-ASNase (Oncaspar) in consolidation treatment of ALL and compared those with data from the previous protocol COALL-05-92. This protocol was similar to COALL-06-97, except that children had been given 45,000 IU/m(2) C-ASNase instead of PEG-ASNase. PATIENTS AND METHODS: Between May 2000 and December 2001 seventy-one children (38 boys, 33 girls) with newly diagnosed ALL treated according to the multicenter protocol COALL-06-97 were investigated in this study. Four hundred and seventy-four plasma samples (71 patients) were analysed by ion exchange chromatography after column derivatization with o-phthaldialdehyde. For comparison data (350 plasma samples) from 51 patients treated according to the protocol COALL-05-92 were available. The same method for detection of asn in plasma was used. RESULTS: The median asparagine level in plasma after 2,500 IU/m(2) PEG-ASNase i.v. was below the limit of detection for at least 5 weeks in 81 % of the patients. When divided into high risk (HR) and low risk (LR) group, HR patients who had previously received one dose more of C-ASNase showed a markedly shorter depletion than the LR patients compatible with a higher risk of antibody formation and consequent silent inactivation after a higher number of exposures to ASNase. In the previous protocol COALL-05-92 median asn levels in plasma after 45,000 IU/m(2) native C-ASNase i.v. were below the limit of detection for at least 5 weeks in 65 % of the patients. CONCLUSIONS: 2,500 IU/m(2) PEG-ASNase led to an equally long depletion of asn in plasma as did 45,000 IU/m(2) native C-ASNase i.v. used in COALL-05-92.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asparaginase/administration & dosage , Asparagine/blood , Polyethylene Glycols/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Chromatography, Ion Exchange , Dose-Response Relationship, Drug , Drug Hypersensitivity/immunology , Drug Hypersensitivity/prevention & control , Female , Half-Life , Humans , Infant , Infusions, Intravenous , Male , Multicenter Studies as Topic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
A mildly retarded infant with failure to thrive developed hypoglycaemia, focal seizures, respiratory failure and hemiparesis during a febrile episode at the age of 16 months. A brain scan was initially normal and showed hemilateral focal edema and gliosis at later stages. 3-Methylcrotonyl-CoA carboxylase deficiency was suggested by elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, and confirmed by enzyme assays. The patient was treated with protein restriction and carnitine and remained stable during the following 5 years. Hemiparesis and some developmental delay persisted. In acute focal brain disease, metabolic disorders must be considered. 3-Methylcrotonyl-CoA carboxylase deficiency adds to the list of possible causes of "metabolic stroke".
Subject(s)
Amino Acid Metabolism, Inborn Errors/complications , Carbon-Carbon Ligases/deficiency , Hemiplegia/etiology , Leucine/metabolism , Amino Acid Metabolism, Inborn Errors/diet therapy , Carnitine/administration & dosage , Diet, Protein-Restricted , Failure to Thrive/metabolism , Female , Gliosis/etiology , Humans , Infant , Intellectual Disability/etiology , Leucine/administration & dosage , Seizures/etiologyABSTRACT
The ISOLAB NCS phenylalanine determination kit has not been widely applied for neonatal screening and patient follow up in Europe until now. This method, based on fluorescence enhancement of a phenylalanine-ninhydrin reaction product by the dipeptide L-leucyl-L-alanine, was compared with three other procedures: (1) The Quantase kit (Shield Diagnostics) for enzymatic determination of phenylalanine, (2) the standard amino acid analysis by means of ion exchange chromatography, and (3) the Guthrie Test as a bacterial inhibition assay (BIA). Only authentic samples from PKU patients were evaluated: once with the NCS kit and at least once with one of the three other methods. There was good agreement between the results obtained by the NCS kit using dried blood specimens and either of the other three methods, as well as between the NCS kit using plasma samples and the Quantase kit and ion exchange chromatography. Plasma sample measurement by NCS proved advantageous because of the option of measuring each microtiter plate twice by resetting the calibrators, i.e. special standards for plasma samples could be used on the same plate. We conclude that this method should prove time saving and cost effective when both neonatal screening and patient follow up are carried out in the same laboratory.