Acute Leukemias - Republican Scientific Medical Library

138 Chapter 10 · Recent Clinical Trials in Acute Lymphoblastic Leukemia by the Cancer and Leukemia Group B
Fig. 10.1. Disease-free survival at 3 years for 611 adults who
achieved a complete remission from ALL after treatment in five
CALGB trials between 1988 and 2001.
Fig. 10.2. Overall survival at 3 years for 759 adults with newly diagnosed
ALL enrolled in five CALGB trials between 1988 and 2001.
dren with high-risk ALL. Other aspects of postremission
therapy were patterned after that used by the adult
German multicenter ALL (GMALL) study group and included
a total of 2 years of scheduled chemotherapy [4].
In this trial, 85% of the 197 evaluable patients (median
age, 32 years; range 16 to 80 years) achieved a CR,
including 94% of patients less than 30 years old, 85%
of patients aged 30–59, and 39% of patients ³60 years
old. The median duration of CR was 2.4 years (95%
CI, 2.0–5.3 years) and was also age-related. Improved results
were noted in patients with T-cell ALL (estimated
3-year survival, 69%) compared to B-lineage ALL (estimated
3-year survival, 38%). The most recent data indicate
that 43% of patients survived > 5 years (95% CI, 36–
50%) and 42% (95% CI, 35–50%) were in continuous CR
(CCR) for >5 years.
In contrast to earlier CALGB studies, there was no
adverse impact on outcome associated with the coexpression
of myeloid antigens [5]. Although the CR rate
was very high, remission induction treatment was complicated
by prolonged granulocytopenia requiring an
average of 26 days of hospitalization. In particular, the
mortality in patients >60 years of age was unacceptably
high, and dose reductions of the cyclophosphamide and
the daunorubicin were implemented for these patients.
Similarly, the first course of consolidation therapy was
also quite myelosuppressive, requiring an average of
14 days of hospitalization during this 2-month treatment.
10.3 CALGB Study 9111
The major cause of treatment-related morbidity and
mortality for patients with ALL is infection due in part
to bone marrow suppression by cytotoxic therapy.
Therefore, the CALGB designed a double-blind, placebo-controlled
clinical trial (9111) to test the effectiveness
of filgrastim (granulocyte colony stimulating factor, G-
CSF) in reducing the complications of treatment by potentially
shortening the time to neutrophil recovery following
courses of remission induction chemotherapy
and postremission consolidation treatment [6].
We randomly assigned 198 adults with untreated
ALL (median age, 35 years; range 16 to 79 years) to receive
either placebo or G-CSF (5 lg/kg/day) subcutaneously,
beginning 4 days after starting the intensive remission
induction chemotherapy and continuing until
the neutrophil count was ³1000/ll for 2 days. The study
assignment was unblinded when individual patients
achieved a CR. Patients initially assigned to G-CSF then
continued to receive G-CSF through 2 monthly courses
of consolidation therapy. Patients assigned to placebo
received no further study drug.
The median time to recover neutrophils ³1000/ll
during the remission induction course was 16 days (interquartile
range (IQR), 15 to 18 days) for the patients
assigned to receive G-CSF and 22 days (IQR, 19–29 days)
for the patients assigned to placebo (p < 0.001). Patients
in the G-CSF group had significantly shorter durations
of neutropenia (< 1000/ll) and of thrombocytopenia
(< 50000/ll) and fewer days in hospital (median, 22
days vs. 28 days, p=0.02) compared to patients receiving
placebo. The patients assigned to receive G-CSF had
a higher CR rate (87% vs. 77%) and fewer deaths during
remission induction (5% vs. 11%) than did those receiving
placebo. During Courses IIA and IIB of consolidation
treatment, patients in the G-CSF group had significantly
more rapid recovery of neutrophils ³1000/ll
than did the control group by approximately 6–9 days.