Acute Leukemias - Republican Scientific Medical Library

148 Chapter 11 · Conventional Therapy in Adult Acute Lymphoblastic Leukemia: Review of the LALA Program
sion (chemotherapy, allogeneic SCT, autologous SCT) in
terms of DFS or survival. However, the number of allocated
patients in each arm was too small to draw any
conclusions. Furthermore, 12 out of the 34 allografted
patients have relapsed, of whom 10 had received T-depleted
marrow.
11.5 LALA-87 Trial (1986–1991)
The previous pilot study has led the LALA group to propose
a new trial (LALA-87 trial) testing the different
strategies for postinduction therapy with the aim to ascertain
clearly the value of transplantation and of chemotherapy
in first CR [15]. The objective was therefore,
first, to evaluate randomly, after consolidation chemotherapy,
the benefits of autologous SCT over classical
maintenance chemotherapy (L10 regimen), and second,
to pursue the evaluation of allogeneic SCT in first remission.
Finally, a randomized evaluation of zorubicin over
daunorubicin as a part of the induction regimen was
performed (Fig. 11.3). This multicentric cooperative trial
was conducted between 1986 and 1991 by 43 French and
Belgian institutions.
In ALL, many attempts have been made to intensify
induction regimens by adding a fourth or a fifth drug
[13, 16, 17], but the actual benefit of this approach remained
questionable. In the LALA-87, we proposed the
administration of a high-dose anthracycline added to
cyclophosphamide in induction therapy. Of the 572 assessable
patients, 76% achieved CR. No differences in
terms of CR, DFS, or survival were observed when considering
the two randomized induction regimens. The
OS rate of the entire cohort was 27% at 10 years [18].
The survival rate for the 436 patients achieving CR
was 30% at 10 years. All patients aged 51–60 years were
treated with chemotherapy only. The 10-year survival of
those patients was 18%. In the LALA-87 trial, assignment
to postremission arm based on the results of
HLA typing was considered as a “genetic randomization”.
Patients with an HLA-matched sibling donor were
assigned to the allogeneic SCT arm, while those without
donor were assigned to the control arm, and then secondarily
randomly allocated to receive autologous SCT
or chemotherapy. In the allogeneic SCT trial, based on
an intent-to-treat analysis, the 10-year survival rate
was 46% in the allogeneic SCT arm vs. 31% in the control
arm (p = 0.04). In the autologous SCT trial, based
on an intent-to-treat analysis, the 10-year survival was
Fig. 11.3. Schema of LALA-87 trial. Induction therapy consisted of
vincristine 1.5 mg/m 2 /d on days 1, 8, 15 and 22; cyclophosphamide
600 mg/m 2 /d on days 1 and 8; and prednisone 60 mg/m 2 /d on
days 1 to 22. In addition, two anthracyclines, either rubidazone
(RBZ) 100 mg/m 2 /d on days 1 to 3 or daunorubicin (DNR) 50 mg/
m 2 /d on days 1 to 3, were compared (R1). In absence of CR, patients
received salvage therapy including cytarabine 500 mg/m 2 /12 h on
days 1 to 4, and amsacrine 120 mg/m 2 /d on days 1 to 3. Consolidation
therapy consisted of three 1-month courses of either rubidazone
120 mg/m 2 on day 1 or daunorubicin 60 mg/m 2 on day 1;
cytarabine 60 mg/m 2 /d on days 3 to 7; and asparaginase 1000 U/
m 2 /d on days 8 to 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 to 8; daunorubicin 60 mg/m 2 on day 15 or
rubidazone 120 mg/m 2 on day 15; vincristine 1.5 mg/m 2 /d on
days 1 and 8; 6-mercaptopurine 60 mg/m 2 /d on days 25 to 56;
methotrexate 15 mg/m 2 /d on days 35, 42, 49 and 56; and dactinomycin
1000 gamma/m 2 on day 64; alternating with 4 cycles of 64
days including prednisone 60 mg/m 2 /d on days 1 to 8; cyclophosphamide
800 mg/m 2 on day 15; carmustine 80 mg/m 2 on day 15;
vincristine 1.5 mg/m 2 /d on days 1 and 8; 6-mercaptopurine 60 mg/
m 2 /d on days 25 to 56; methotrexate 15 mg/m 2 /d on days 35, 42, 49
and 56; and dactinomycin 1000 gamma/m 2 on day 64. Abbreviations:
AlloSCT, allogeneic stem cell transplantation; Amsa, amsacrine;
AraC, cytarabine; Autologous SCT, autologous stem cell
transplantation; CNS, central nervous system; DNR, daunorubicin;
RBZ, rubidazone; R1, first randomization; R2, second randomization.
34% in the autologous SCT arm vs. 29% in the chemotherapy
arm (p =NS). Overall results were in the
range of those published by most larger cooperative
groups. The LALA-87 confirmed the efficacy of allo-