Acute Leukemias - Republican Scientific Medical Library

a 11.7 · LALA-94 Trial (1994–2002) 149
geneic SCT [19–21]. In the second trial comparing autologous
SCT and chemotherapy, there was only a trend
for better results in the autologous SCT arm.
11.6 LALA-91 Pilot Study (1991–1993)
Between 1991 and 1993, 57 patients were included in a
pilot multicenter trial in which we used sequential administration
of prednisone from day 1 to day 7, and
day 15 to day 21, in combination with a conventional
chemotherapy combining vincristine, daunorubicin,
and cyclophosphamide, with the aim of decreasing the
risk of complications in relation with steroid administration
[22]. A high rate of CR (89%) was observed
without severe toxicity. Severe infectious complications
occurred in only 14% of cases. Sequential use of prednisone
seemed at least as effective as continuous administration
at the expense of a few adverse side effects and
was therefore included in the further trials (LALAG-92
and LALA-94).
11.7 LALA-94 Trial (1994–2002)
The prognosis of adult patients with ALL, treated with
modern chemotherapeutic regimens, is dependent on
a number of variables. These features have been utilized
to identify patients with low and high risk of relapse.
Treatment tailored to individual risk groups has resulted
in dramatic improvements in outcome for pediatric patients
with ALL, and risk-adapted strategies based on
biological and clinical features were also applied to
adults with ALL to improve survival. The major prognostic
factors in adults are age, cytogenetics, immunologic
subtype, white blood cell count, and time to
achieve CR [23]. Risk-adapted strategy is based on a
dose efficacy scheme and the optimal treatment strategy
is related to a perfect knowledge of prognostic factors.
However, prognostic factors are regimen-dependent
and could therefore change according to the period of
study.
Based on the LALA-87 trial results [15], aggressive
induction plus more potent intensification programs
with chemotherapy plus SCT have been proposed to improve
treatment results. We introduced in the LALA-94
trial a risk-adapted postremission strategy according to
initial features and to initial response to therapy, and we
re-evaluated transplantation for high-risk ALL [24]. Be-
tween 1994 and 2002, a total of 1000 untreated ALL patients
(excluding mature B-cell ALL) from 68 French,
Belgian, Swiss, and Australian centers entered the
LALA-94. All patients received a standard 4-drug/4week
induction course. After one course of induction
chemotherapy, patients were systematically stratified,
by initial clinical and biological characteristics (based
on cytogenetic analysis and molecular examination)
and by their response to initial therapy, in different risk
groups. Postinduction intensity was designed according
to the risk level (Fig. 11.4). Standard-risk ALL comprised
all T-cell lineage ALL patients achieving CR after
one course of chemotherapy and B-cell lineage ALL patients
defined by the absence of CNS-positive ALL, the
absence of Philadelphia chromosome, t(4;11), t(1;19), or
other abnormalities involving 11q23 rearrangements, a
white blood cell count < 30 ´10 9 /l, an immunophenotype
characterized by CD10 + /CD19 + , or CD20 + /CD19 +
and the absence of myeloid markers, and achievement
of CR after one course of chemotherapy. Standard-risk
ALL followed a chemotherapy program for 2 years with
a randomization on day 35 between either an intensive
consolidation chemotherapy, combining mitoxantrone
and intermediate-dose cytarabine (HAM), followed by
maintenance therapy or only maintenance chemotherapy.
Philadelphia chromosome-positive ALL and CNSpositive
ALL were individualized. On the basis of intention-to-treat
principle, these patients achieving CR,
after an induction course followed by HAM intensive
consolidation, were distributed in one of the following
groups: matched related allogeneic SCT if they had a
sibling donor, or autologous SCT if they did not meet
criteria for the first group. High-risk ALL was defined
as nonstandard-risk ALL without Philadelphia chromosome
or CNS involvement. In this group, all patients
with a HLA sibling were scheduled for allogeneic SCT.
Patients without a sibling donor were randomly assigned
between the chemotherapy program and autologous
SCT.
Report on 922 eligible patients showed a CR rate of
84%. Median OS was 23 months and median DFS was
17.5 months with 3-year DFS at 37%. In standard-risk
ALL, the 3-year DFS rate was 41%, with no difference
between arms of postremission randomization. In
high-risk ALL and ALL with CNS involvement, the 3year
DFS rates were 38% and 44%, respectively. In
high-risk ALL, autologous SCT and chemotherapy resulted
in not significantly different outcome. Patients
with an HLA-matched sibling had improved DFS [24].