Asparagine depletion after pegylated E. coli asparaginase treatment and induction outcome in children with acute lymphoblastic leukemia in first bone marrow relapse: a Children's Oncology Group study (CCG-1941).
Pediatr Blood Cancer
; 47(2): 141-6, 2006 Aug.
Article
en En
| MEDLINE
| ID: mdl-16425271
PURPOSE: Re-induction outcomes vary for children with acute lymphoblastic leukemia (ALL) and marrow relapse. We explored possible relationships among asparaginase (ASNase) activity levels, asparagine (ASN) depletion, anti-ASNase antibody titers, and response to re-induction therapy in children and adolescents with ALL and an 'early' first marrow relapse. PATIENTS AND METHODS: After appropriate informed consent, we enrolled children and adolescents 1-21 years old with ALL and first marrow relapse within 12 months of completion of primary therapy. Induction therapy included intramuscular pegylated ASNase on Days 2 and 16. We assessed ASNase activity, anti-ASNase antibody titers against native and pegylated (E. coli) ASNase, and amino acid levels of asparagine (ASN) and glutamine (GLN) on Days 0, 14, and 35 of re-induction. RESULTS: Ninety-three patients were at least partially assessable. Among 21 patients with M1 marrow status at Day 35, the median Day 14 ASN level was <1 microM. This is significantly lower than the median Day 14 ASN level of 4 microM in the group of patients with M3 marrow at Day 35. Neither Day 0 nor Day 35 antibody titers predicted ASNase enzymatic activity level on Day 14. Surprisingly, Day 14 ASNase activity did not predict serum ASN level on Day 14. However, Day 0 and Day 35 anti-native ASNase antibody titers, and Day 0 anti-PEG ASNase antibody titers correlated positively with Day 14 serum ASN levels as one might expect from neutralizing antibody. Day 35 anti-PEG ASNase antibody titers did not. CONCLUSIONS: Patients with greater ASN depletion were more likely to achieve second remission in the context of six-drug therapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Asparaginasa
/
Asparagina
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Blood Cancer
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos