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Treatment for Newly Diagnosed Childhood ALL

    continued...

    Patients with an allergic reaction to PEG-L-asparaginase should be switched to Erwinia L-asparaginase.

    Pharmacokinetics and toxicity profiles are similar for IV and IM PEG-L-asparaginase administration.[22] The toxicity of PEG-L-asparaginase seems to be similar to that observed with native E. coli asparaginase. It is safe to give IV PEG-L-asparaginase in pediatric patients.[21,22]

    ErwiniaL-asparaginase:

    The half-life of Erwinia L-asparaginase (0.65 days) is much shorter than that of native E. coli (1.2 days) or PEG-L-asparaginase (5.7 days).[19] If Erwinia L-asparaginase is utilized, the shorter half-life of the Erwinia preparation requires more frequent administration and a higher dose to achieve adequate asparagine depletion.

    Evidence (Erwinia L-asparaginase):

    1. In two studies, newly diagnosed patients were randomly assigned to receive the same schedule and dosage of Erwinia L-asparaginase or E. coli L-asparaginase.[24,25]
      • Patients who received Erwinia L-asparaginase had a significantly worse EFS.
      • When administered more frequently (twice weekly), the use of Erwinia L-asparaginase did not adversely impact EFS in patients experiencing an allergic reaction to E. coli L-asparaginase.[26]

    Response to remission induction chemotherapy

    More than 95% of children with newly diagnosed ALL will achieve a complete remission (CR) within the first 4 weeks of treatment. Of those who fail to achieve CR within the first 4 weeks, approximately half will experience a toxic death during the induction phase (usually due to infection) and the other half will have resistant disease (persistent morphologic leukemia).[25,27,28]; [29][Level of evidence: 3iA] Patients with persistent leukemia at the end of the 4-week induction phase have a poor prognosis and may benefit from an allogeneic stem cell transplant (SCT) once CR is achieved.[30,31,32] In a large retrospective series, the 10-year overall survival for patients with persistent leuekmia was 32%.[33] A trend for superior outcome with allogeneic SCT compared with chemotherapy alone was observed in patients with T-cell phenotype (any age) and B-precursor patients younger than 6 years. B-precursor ALL patients who were aged 1 to 5 years at diagnosis and did not have any adverse cytogenetic abnormalities (MLL translocation, BCR-ABL) had a relatively favorable prognosis, without any advantage in outcome with the utilization of SCT compared with chemotherapy alone.[32]

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