Acute Leukemias - Republican Scientific Medical Library

146 Chapter 11 · Conventional Therapy in Adult Acute Lymphoblastic Leukemia: Review of the LALA Program
into the biologic and molecular abnormalities in ALL
might also provide the necessary clues that allow a
clearer understanding of the crucial differences in the
behavior of the different subtypes of ALL patients.
11.2 General Principles
In the 1960s, a major development in the treatment of
ALL came from St. Jude Children’s Research Hospital
in Memphis, with Don Pinkel introducing a four-phase
treatment plan for ALL, what he called “Total therapy”
[1] that took into account the advantage of combination
chemotherapy in overcoming initial drug resistance and
inhibiting acquired resistance, as well as the superiority
of some drugs for remission induction and others for its
continuation. All available antileukemic agents were included
in the plan. The principles that were applied resulted
in the regular cure of more than 50% of children
with ALL. These principles were induction therapy
using vincristine and prednisone, consolidation chemotherapy,
a maintenance chemotherapy using 6-mercaptopurine
and methotrexate, and then radiotherapy
to the central nervous system (CNS) to prevent meningeal
relapse. This resulted in a tremendous increase in
the survival rate of patients with ALL. This regimen also
recognized the importance of early intensification chemotherapy,
the need for specific CNS treatment to prevent
meningeal relapse, and the idea of continuing combination
chemotherapy for 2 to 3 years. With this basic
therapeutic strategy, results improved regularly over
time with complete remission (CR) rates above 90%
with recent programs and survival approaching 70–
80% [2]. Unfortunately, the success that has been
achieved in children with ALL has not yet been translated
into adult patients [3]. Although CR rates
approach now those in children, only 30–40% of adults
with ALL can expect a cure 4. Less frequent than ALL in
childhood, ALL in adults has long been mishandled [4,
5]. The first cooperative studies in adults with ALL were
initiated during the 1970s and the early 1980s [6–9], of
which the first trial of the LALA group.
11.3 LALA-83 Trial (1983–1985)
A pilot study on 45 patients from 16 to 73 years old was
initiated in 1982 to test the feasibility of an intensive and
short induction phase followed by an early consolida-
tion phase [10]. Eleven French centers participated to
that pilot study. All patients received a 5-day course of
induction chemotherapy with prednisone, vincristine,
cytarabine, and rubidazone. An “AAA” regimen consisting
of Adriamycin, cytarabine (Aracytine), and Asparaginase
was used as consolidation. CR was achieved in
73% of patients and the sequence intensive inductionearly
consolidation was well tolerated and proved feasible.
This allowed the development of a larger multicenter
trial. The LALA-83 trial started at the beginning of
1983 and ran through 1985, including 225 patients from
33 French centers. The major aims of this trial were to
study the usefulness of aggressive CR induction and
Fig. 11.1. Schema of LALA-83 trial. Induction therapy consisted of
VRAP with rubidazone 450 mg/m 2 /d on day 1; vincristine 1.2 mg/
m 2 /d on days 1 and 5; cytarabine 100 mg/m 2 /d on days 1–5; and
prednisone 80 mg/m 2 /d on days 1–5; or VCP with vincristine
1.4 mg/m 2 /d on days 1, 8, 15, and 21; cyclophosphamide 400 mg/
m 2 /d on days 1, 8, 15, and 21; and prednisone 60 mg/m 2 /d on
days 1–15. Consolidation therapy consisted of three 1-month
courses of adriamycin 40 mg/m 2 on day 1; cytarabine 60 mg/m 2 /d
on days 3–7; and asparaginase 1000 U/m 2 /d on days 8–12. Maintenance
chemotherapy consisted of methotrexate 15 mg/m 2 /week
and 6-mercaptopurine 90 mg/m 2 /d for 2 years. Alternating courses
of reinduction consisting of either vincristine 1.4 mg/m 2 on day 1;
cyclophosphamide 600 mg/m 2 on day 1; and prednisone 60 mg/
m 2 /d on days 1–8; or adriamycin 40 mg/m 2 on day 1; and cytarabine
60 mg/m 2 /d on days 1–5, were performed. Abbreviations:
CNS, central nervous system; R1, first randomization; R2, second
randomization.