Acute Leukemias - Republican Scientific Medical Library

a 11.10 · Treatment of Elderly Patients 153
Fig. 11.6. LALA trials in the elderly. Abbreviations: AraC, cytarabine;
CPM, cyclophosphamide; DNR, daunorubicin; IFN, interferon-a;
HAM, intermediate-dose cytarabine + mitoxantrone; Imatinib, imatinib
mesylate; Lasp, L-asparaginase; Mitox, mitoxantrone; MTX,
quantitative defect of endogenous IFN may be involved
in the pathogenesis of ALL [50]. From 1992 to 1995, 40
patients from 11 French and Belgian centers were included
in the LALAG-92 study [46]. Compared with
younger adults treated according to the LALA-87 protocol,
elderly patients did not present with more adverse
prognostic features, except for a lower incidence of Tcell
ALL. After completion of induction therapy, 85%
achieved a CR, while treatment-related mortality during
induction was 7.5%. Median OS and DFS were 14.3
months and 14 months, respectively, which, although
inferior to results obtained in younger adults, compared
favorably with available data in the elderly. Treatment
with IFN proved feasible in most patients, but had to
be discontinued in 32% of cases because of toxicity.
In 1997, The LALA group initiated a study (LALAG-
97) derived from the 1992 study, with as main purposes
to better understand the value of IFN and to assess the
toxicity and the impact on OS of an intensified induction
and of a double consolidation (Fig. 11.6). At inclusion,
patients were randomly allocated to therapy with
mitoxantrone; PDN, prednisone; R, randomization; VAD, vincristine +
adriamycin + dexamethasone; VCR, vincristine; VDS, vindesine; 6MP,
6-mercaptopurine.
vincristine or with vindesine during induction and
the dose of daunorubicin was increased. The consolidation
phase was intensified. A 3-month course of IFN was
started after the first consolidation phase. A second consolidation
phase and maintenance were given after IFN
therapy. From 1997 to 1999, 58 patients were included in
this study [51]. A CR was obtained in 58% of patients.
OS and DFS were also inferior to those observed in
the previous trial [46]. The pattern of relapses over time
suggested that the 3-month IFN treatment phase with no
additional chemotherapy might have contributed to the
comparatively poor outcome of this cohort.
Despite the poor prognosis in this type of leukemia,
improvements have been observed over time. The development
of supportive care and the introduction of
growth factors could have been responsible for notable
improvements in outcome related to complete applications
of proposed treatment schedules. This was also
probably due to an improvement of specific therapy
against leukemia. “Personalized” treatments, administered
until 1987, have been progressively given up, and