Acute Leukemias - Republican Scientific Medical Library

a 15.4 · Current Treatment of Newly Diagnosed L 3ALL in Adults 193
or “lymphoma regimens” combining relatively moderate
doses of cyclophosphamide (CPM), ANTHR, VCR,
and PR plus “conventional” CNS prophylaxis, that could
cure localized BL, were not sufficient to eradicate systemic
and CNS disease in disseminated BL and L 3ALL
[27–30] (HD MTX, 3 g/m 2 ). Several groups then showed
that considerable improvement in the outcome of disseminated
BL and L 3ALL in children could be obtained.
The St. Jude’s group, French SFOP, and German BFM
group introduced treatment protocols that included, in
particular, fractionated high doses of CPM (or ifosfamide),
intermediate or high dose (HD) methotrexate
and Ara C, and VM26 or VP16 in addition to doxorubicin
and VCR (Tables 15.1, 15.2). Very early CNS treatment,
with repeated intrathecal therapy and CNS irradiation
(which could often be replaced by courses of
HD-MTX at 3 g/m 2 ) was added to reduce the incidence
of CNS disease.
Those groups also showed that, in order to reduce
the risk of potentially lethal tumor lysis syndrome,
treatment had to start by a small dose (“prephase,” generally
combining CPM, VCR, and PR), high-dose chemotherapy
being usually started 1 week later. The combination
of urate oxidase with induction therapy can
also reduce the risk of severe renal injury during early
phase of induction therapy [31]. With these intensified
protocols, and introduction of a treatment prephase,
the prognosis of stage III and stage IV BL had greatly
improved, 70–75% of the patients achieving cure. This
large pediatric experience also showed that virtually
no relapse occurred after 1 year of diagnosis.
However, patients with CNS involvement and
L 3ALL still had poor outcome using such protocols
and had many relapses involving in particular the
CNS, and finally cure rates of only 20–30%. This led
to start approaches using further intensification of
CNS treatment with HDMTX (at 5 g/m 2 in BFM trials
and 8 g/m 2 in SFOP trials), a greater number of triple
intrathecal injections (with AraC, MTX, hydrocortisone),
consolidation with VP16 and HD Ara C, and
cranial irradiation [28, 32, 33]. With those protocols,
about 75% of BL with CNS involvement and L 3ALL
could be cured in the experience of the French SFOP
and the German BFM group. Those results were recently
confirmed by a UK group, using a SFOP protocol
[34].
15.4 Current Treatment of Newly Diagnosed
L 3ALL in Adults
The approaches that showed improved results in children
were rapidly proposed to adults. In particular,
the SFOP and BFM protocols were applied to adults,
with no or minor modifications (Tables 15.1, 15.2).
Groups involved in the treatment of adult ALL also used
the bases of those protocols to adapt their treatment of
L 3ALL. Results of the published experience with such
treatments are shown in Table 15.3.
Application of those reinforced protocols to adult
L 3 ALL rapidly led to improved results. For example,
all the seven adult L 3ALL patients treated by our
group from 1981 to 1984 with conventional (or with
slightly reinforced CNS prophylaxis) ALL protocols
died within 1 year of diagnosis [18]. By contrast, six of
the nine subsequent adult L 3ALL cases, treated by
SFOP 86 protocol, were cured of their disease. Favorable
results of SFOP programs, especially SFOP 86
protocol in adult L 3ALL, were more recently confirmed
by Soussain et al. in 24 patients [35]. Nineteen of them
achieved CR, and 14 of them were alive in prolonged
first CR. Importantly, eight of the 18 patients who
achieved CR in that series were allografted (six cases)
or autografted (two cases) in first CR. Three of them
died from toxicity, two relapsed and only three were
cured of their disease. By comparison, all the 11 patients
consolidated with chemotherapy alone remained
disease free. This transplantation series may have had
especially poor results, notably when compared with a
previous French series of allogeneic BMT performed
in first CR in adult BL with initial CNS and/or marrow
involvement, where seven of nine patients had favorable
outcome [36]. Still, results of Soussain, et al. and
the recent EBMT series [37] suggest that intensification
with an allo or autograft is not justified in L 3ALL in
first CR.
Pees et al. [38] and Todeschini et al. [39] also applied
childhood BL and L3ALL trials to adults (BFM-NHL and
POG protocols, respectively) with favorable results,
although on smaller numbers of cases. POG 86 trial
consists of six courses alternating a cycle A and a cycle
B, which are largely similar to BFM-NHL trials, but include,
like SFOP 86 trial, HDAraC. Magrath et al. [33]
also found that adults with disseminated BL treated with
a childhood BL protocol that included the same drugs at
similar doses as BFM and SFOP trials achieved as favorable
results as with children.