PMID- 16425271
OWN - NLM
STAT- MEDLINE
DCOM- 20060816
LR  - 20181201
IS  - 1545-5009 (Print)
IS  - 1545-5009 (Linking)
VI  - 47
IP  - 2
DP  - 2006 Aug
TI  - 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).
PG  - 141-6
AB  - 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.
FAU - Jarrar, Mohammad
AU  - Jarrar M
AD  - Department of Pediatrics, Division of Hematology/Oncology, USC Keck School of 
      Medicine, Childrens Hospital Los Angeles, Los Angeles, California, USA.
FAU - Gaynon, Paul S
AU  - Gaynon PS
FAU - Periclou, Antonia P
AU  - Periclou AP
FAU - Fu, Cecilia
AU  - Fu C
FAU - Harris, Richard E
AU  - Harris RE
FAU - Stram, Daniel
AU  - Stram D
FAU - Altman, Arnold
AU  - Altman A
FAU - Bostrom, Bruce
AU  - Bostrom B
FAU - Breneman, John
AU  - Breneman J
FAU - Steele, David
AU  - Steele D
FAU - Trigg, Michael
AU  - Trigg M
FAU - Zipf, Theodore
AU  - Zipf T
FAU - Avramis, Vassilios I
AU  - Avramis VI
LA  - eng
PT  - Clinical Conference
PT  - Journal Article
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (Antineoplastic Agents)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 7006-34-0 (Asparagine)
RN  - 7D96IR0PPM (pegaspargase)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Antibody Formation/drug effects
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Asparaginase/administration & dosage/immunology/*pharmacology
MH  - Asparagine/*drug effects/metabolism
MH  - Child
MH  - Female
MH  - Glutamic Acid/drug effects/metabolism
MH  - Humans
MH  - Injections, Intramuscular
MH  - Male
MH  - Polyethylene Glycols/administration & dosage/*pharmacology
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/pathology
MH  - Recurrence
MH  - Remission Induction
MH  - Statistics, Nonparametric
EDAT- 2006/01/21 09:00
MHDA- 2006/08/17 09:00
CRDT- 2006/01/21 09:00
PHST- 2006/01/21 09:00 [pubmed]
PHST- 2006/08/17 09:00 [medline]
PHST- 2006/01/21 09:00 [entrez]
AID - 10.1002/pbc.20713 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2006 Aug;47(2):141-6. doi: 10.1002/pbc.20713.