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34 Acute Lymphoblastic Leukemiatreatment (e.g., impact of agents that alter CYPA4 and other p450
enzymes, agents that may alter plasma pharmacokinetics and intra-
cellular concentrations of major antineoplastic agents).
■Treatment of leukemia should proceed expeditiously, but metabolic
stabilization of the patient may be advisable (for a short period) if
the disease is not rapidly progressing or if bulk disease is not criti-
cally impinging on vital structures. If disease is rapidly progressing,
leukopheresis may be helpful for symptoms of hyperleukocytosis,
and initiation of systemic chemotherapy should then begin as soon
as possible.Risk-Based Therapeutic Strategies
■Prognostic Features & Risk Assessment
■Several clinical features are associated with a poor outcome, includ-
ing patient age (e.g.,<1 year old or>50–60 years old); WBC at
presentation (>50,000); time to remission; patients who have resid-
ual disease detected by flow or PCR determination of clonal geno-
typic abnormalities (at level 0.1% or greater)after being in remis-
sion have a high cumulative risk for relapse. Specific cytogenetic
abnormalities confer a worse prognosis, including the following: pts
w/ t:(9;22) or bcr-abl expression by molecular screening have poor
long-term outcome; pts w/ t:(4;11) with MLL-AF4A fusion gene have
a worse long-term prognosis; patients with hypodiploidy (< 45 chro-
mosomes/leukemic cell) have a worse prognosis than those with
hyperdiploidy (>50 chromosomes/leukemic cell). Patients with the
t(12;21) with the TEL-AML1 fusion gene have a favorable prognosis.
In patients with T-cell ALL, the presence of t(11;19) with MLL-ENL
fusion and overexpression of the HOX11 gene confers a good prog-
nosis.
■Patients with standard-risk ALL are treated with multiagent
induction therapy (vincristine, prednisone, cyclophosphamide, L-
asparaginase, and an anthracycline); standard-risk patients require
consolidation with CNS treatment (may include CNS irradiation
and intrathecal chemotherapy) followed by late intensification with
chemotherapy and maintenance chemotherapy for a total duration
of therapy from 2.5 to 3 years. Additional agents used during inten-
sification therapy following achievement of a complete remission
include cyclophosphamide, high-dose methotrexate, mercaptop-
urine, and cytosine arabinoside. Different intensification and con-
solidation regimens have been used but often include drugs other
than those received during initial induction.