Acute Leukemias - Republican Scientific Medical Library

132 Chapter 9 · General Approach to the Therapy of Adult Acute Lymphoblastic Leukemia
include addition of known chemotherapy drugs or
further intensification of chemotherapy doses, but also
incorporation of new and targeted drugs (e.g., monoclonal
antibodies and tyrosine kinase inhibitors), reassessment
of the position of stem cell transplant as part of
consolidation in first remission, use of molecular monitoring
for minimal residual disease, and hence establishment
of novel prognostic systems leading to more
patient-specific therapy approaches based on risk profile
and ALL subset (Table 9.1).
The backbone of induction therapy consists of vincristine,
steroids, and anthracyclines to which various
other drugs such as L-asparaginase, cyclophosphamide,
or cytarabine have been added. Dexamethasone has replaced
prednisone for better antileukemia activity and
achievement of higher levels in the CSF [5, 6]. Retrospective
studies suggested that early dose intensification
of daunorubicin would lead to superior leukemia-free
survival and cure rates. Italian investigators used three
cycles of daunorubicin at 30 mg/m2/day for 3 days for
a total of 270 mg/m2 during induction [7]. They reported
long-term disease-free survival (DFS) of 55%.
Other studies have not confirmed an improvement in
DFS, but noted fewer relapses after 2 years [8]. Highdose
cytarabine and mitoxantrone or even single-agent
high-dose idarubicin without the traditional vincristine-steroid
combination as the basic therapy have been
investigated, but there is little evidence of their advantage
[9, 10]. Overall, it has been difficult to prove higher
remission rates with these strategies. However, intensified
induction may result in better quality responses
and longer survival in subsets of patients. Maximum
supportive care is a significant contributor to the success
of induction therapy. Use of antibiotics including
antifungal prophylaxis, laminar air flow rooms for older
patients (³60 years), and hematopoietic growth factors
permit administration of dose-intensive therapy with
relatively low induction mortality due to myelosuppression-associated
complications. The Cancer and Leukemia
Group B (CALGB) randomized untreated ALL patients
to receive either G-CSF or placebo during intensive
remission induction therapy [11]. Patients who
received G-CSF experienced a shorter time to recover
the neutrophil count ³1´109/L (16 days vs. 22 days,
p