Acute Leukemias - Republican Scientific Medical Library

a 11.4 · LALA-85 Trial (1985–1986) 147
early consolidation in adult ALL, and to study the value
of HLA-matched allogeneic stem cell transplantation
(SCT) performed in early first CR (Fig. 11.1) [11]. One
third of the patients were randomized in the VCP (vincristine,
cyclophosphamide, prednisone) induction
arm, while two thirds in the more aggressive VRAP
(vincristine, rubidazone, cytarabine, prednisone) arm.
CR rates were not statistically different with, however,
a higher toxicity in the VRAP arm. Overall, the CR rate
after one or two courses of induction therapy was 77.5%.
Of patients evaluable for postremission therapy, 39 of 42
patients with a suitable donor were allografted in first
CR, 39 patients initially treated by VCP arm received
consolidation with 3 monthly courses of “AAA,” followed
by a 3-year maintenance therapy, 63 patients initially
treated by VRAP arm were randomized to receive
AAA consolidations and maintenance therapy, or only
maintenance therapy. The median overall survival
(OS) was 13.5 months for the entire cohort. The best results
were observed after allogeneic SCT with 6-year disease-free
survival (DFS) at 53% [12]. There was a significantly
better survival for patients initially treated with
VCP and receiving AAA consolidations followed by
maintenance therapy. In the multivariate analysis, age
(cut-off at 35 years) and initial white blood cell count
(cut-off at 30´10 9 /l) appeared as the main prognostic
factors suggesting their use in a risk model further developed
in subsequent trials.
11.4 LALA-85 Trial (1985–1986)
At the beginning of the 1980s, the overall probability of
achieving CR exceeded 75%, and approximately 35% of
patients achieving CR could be cured using chemotherapy
alone [7, 13]. It was therefore appropriate to study
alternative forms of treatment such as allogeneic or
autologous SCT. In the LALA-83 trial, allogeneic SCT
was performed in all patients aged under 40 years having
an HLA-identical sibling, showing a slight advantage
of SCT over optimal chemotherapy [12]. The LALA
group tested, in this pilot study, the feasibility of purged
autologous SCT, after an intensive induction regimen in
which zorubicin was used instead of the classical daunorubicin
(Fig. 11.2) [14]. The postinduction chemotherapy
arm began with 3-month consolidation according
to AAA regimen. The maintenance chemotherapy
was similar to that of the L10 maintenance regimen,
using eight drugs sequentially [4]. In patients, aged 15 to
Fig. 11.2. Schema of LALA-85 trial. Induction therapy consisted of
rubidazone 100 mg/m 2 /d on days 1–3; vincristine 1.4 mg/m 2 /d on
days 1, 8, and 15; cyclophosphamide 400 mg/m 2 /d on days 1, 8, and
15; 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 a modified L10 regimen for 4 cycles of 64 days including prednisone
60 mg/m 2 /d on days 1–8; adriamycin 20 mg/m 2 on days
15–17; vincristine 1.4 mg/m 2 /d on days 1 and 8; 6-mercaptopurine
60 mg/m 2 /d on days 25–56; methotrexate 20 mg/m 2 /d on days 35,
42, 49, and 56; and dactinomycin 1000 gamma/m 2 on day 56; alternating
with 4 cycles of 64 days including prednisone 60 mg/m 2 /d
on days 1–8; cyclophosphamide 800 mg/m 2 on day 15; carmustine
80 mg/m 2 on day 15; vincristine 1.4 mg/m 2 /d on days 1 and 8;
6-mercaptopurine 60 mg/m 2 /d on days 25–56; methotrexate
15 mg/m 2 /d on days 35, 42, 49 and 56; and dactinomycin
1000 gamma/m 2 on day 56. Abbreviations: R1, first randomization.
50 years, without identical sibling donor, the chemotherapy
arm was randomly compared to autologous
SCT. Ex vivo purging of the stem cells was performed
using mafosfamide or monoclonal antibodies plus complement.
From May 1985 to December 1986, 164 patients
from 33 institutions entered the trial. The overall CR
rate was 83%. For the whole group, DFS was 34% and
OS 42% with a median follow-up of 30 months [14].
Twenty-seven patients received autologous SCT. No difference
appeared between the three arms of postremis