Acute Leukemias - Republican Scientific Medical Library

a 16.10 · Summary and Future Prospects 211
In this study, however, the overall CR rate of 56% and the
DFS for chemotherapy were suboptimal [50].
It is a well-known fact that results of chemotherapy
and SCT cannot be easily compared since retrospectively
analyzed SCT patients generally represent a selected
patient cohort excluding patients not achieving
CR, with early relapse or poor general condition. Particularly
patients with LBL generally achieve remission
rapidly and if they relapse, they do it early. Thus it
can be assumed that these patients are not represented
in the transplantation cohort and that a significant
number of the transplanted patients are already cured
by previous chemotherapy.
A recent study tried to circumvent these issues by an
intent-to-treat analysis. In 34 T-LBL patients, SCT was
planned upfront after an NHL/ALL-type induction regimen.
SCT was actually realized in 29 patients (24 auto,
4 allo), which is a high proportion. The overall survival
was 72% for all patients and 79% for those who actually
proceeded to SCT. For auto SCT the DFS is 69% [34].
This is the first study showing convincingly that auto
SCT may yield similar results as chemotherapy in an intent-to-treat
analysis.
16.8.5 Summary
Auto or allo SCT may confer an advantage in survival for
high-risk LBL. However, in recent studies survival after
chemotherapy is similar to the reported results of allo
or auto SCT; furthermore, no convincing risk model
for LBL is available at present and therefore clear indications
for SCT in first CR are missing. Particularly for
allo SCT results are still scarce and treatment-related
morbidity and mortality is high; it should therefore
probably be restricted to relapse patients.
16.9 Outcome of Salvage Therapy
The outcome of patients with relapsed LBL was poor in
most studies. The disease generally shows a rapid progression
and response rates after salvage chemotherapy
are low. Results of auto SCT are also inferior beyond first
CR (Table 16.4). In a report from the EBMTR, the DFS
for auto SCT in CR2 or in resistant disease was 31 and
15%, respectively, compared to 63% in CR1 [48]. Also
in another large cohort, the DFS after auto SCT in
CR1 was 76% compared to 38% for CR2 [49]. From sin-
gle studies DFS rates between 14 and 50% have been reported
for auto SCT in CR2 [14, 46, 55]. For allo SCT beyond
first CR the DFS was low (16%), which seems to be
a realistic result.
The major problem is to achieve a stable second remission.
Several new treatment options may be evaluated.
Salvage treatment should aim to refer the patients
to an allo SCT as soon as possible. In patients without a
compatible donor auto SCT in second remission is an
option if stem cells are available or may be performed
as interim therapy before allo SCT. Therefore storage
of peripheral stem cells during front-line treatment appears
to be reasonable since particularly in patients
without a sibling donor, the search for an unrelated donor
may be too time-consuming.
16.10 Summary and Future Prospects
For the development of future treatment strategies in
adult LBL various questions remain open since no randomized
studies are available. The use of ALL-type regimens
appears to be justified although a prospective
comparison with intensive NHL regimens is desirable.
In this rare disease this aim could, however, only be
achieved with large cooperative studies.
The requirement for intensive prophylaxis of CNS
relapse in T-LBL is evident. It remains, however, open
whether this aim can be achieved by intensive intrathecal
therapy and systemic high dose chemotherapy,
whether CNS irradiation is required or whether it
may be restricted to patients with stage III/IV disease.
The major problem of local disease control is the effective
treatment of mediastinal tumors. This may be
achieved by increased dose for mediastinal irradiation,
although this approach may compromise further chemotherapy
due to bone marrow suppression.
At the same time intensification of systemic treatment
can be attempted since treatment-related mortality
is generally low in LBL. The value of cytostatic drugs
with particular effectivity in T-ALL should be analyzed.
From adult T-ALL it is known that CYCLO and ARAC
contributed to an improvement of overall results [29].
In childhood T-ALL intensive use of asparaginase [56]
and MTX [57] contributed to better outcome. In T-
LBL superior results were attributed to intensive treatment
including cyclophosphamide, MTX, and dexamethasone
during early phase of treatment. As a result
no relapses occurred later than 1 year compared to