Acute Leukemias - Republican Scientific Medical Library

a 16.6 · Mediastinal Tumors 207
Center, CR rates of 80% and DFS of 45% could be
achieved with different ALL-type regimens (L2, L10,
L17) [30]. Similar or even better results with CR rates
between 55 and 100% and DFS rates between 45 and
67% were reported later for ALL-type regimens [9, 11,
12, 14–16, 31, 32].
16.4.2.1 MDACC
The MD Anderson Cancer Center (MDACC) reported
the results of 33 patients treated according to the Hyper-CVAD
regimen. The schedule is based on alternating
cycles with fractionated cyclophosphamide (CY-
CLO) combined with other drugs and cycles with HD-
ARAC and methotrexate (HD-MTX). The majority of
patients received consolidative mediastinal irradiation
after eight cycles. The cohort included mainly T-LBL
(80%) with 70% stage III-IV disease.
The CR rate was 91% with 9% partial responses. The
progression-free survival at 3 years was 66% and the
survival 70% with 62% and 67% for the T-cell subtype,
respectively. The major relapse localization was the mediastinum
(50% of the relapses). Ten percent of the CR
patients developed CNS involvement at relapse. Except
CNS involvement at diagnosis, no prognostic factors
could be identified [18].
16.4.2.2 GMALL
The largest cohort of T-LBL was reported by the German
Multicenter Study Group for Adult ALL (GMALL).
Forty-five patients were treated with standard 8-drug
induction including prophylactic CNS irradiation and
mediastinal irradiation followed by consolidation and
reinduction therapy. In the majority of patients, treatment
ended after reinduction at about 30 weeks.
The CR rate was 93%. Thirty-six percent of the patients
relapsed. No late relapses after the first year from
diagnosis were observed. The majority of relapses
(47%) involved the mediastinum, although six out of
seven patients had received mediastinal irradiation with
24 Gy. The survival was 51% at 7 years, 65% for CR patients,
and the DFS was 62%. Advanced stage, age, LDH
and other parameters had no prognostic impact [11].
16.4.3 Summary
These studies provide strong evidence that intensive
chemotherapy in T-LBL may lead to favourable outcome
without SCT in first CR even in patients with advanced
disease and that particularly late relapses may be
avoided to a large extent. Additional evidence for the
high effectivity of ALL-type chemotherapy in T-LBL
comes from a report on 105 children with T-LBL. The
event-free survival of 90% was superior to previous
studies in childhood T-LBL [7].
16.5 CNS Prophylaxis
Initial CNS involvement is observed in approximately
7% of LBL patients, which is similar to the incidence
in ALL [11, 12, 14, 18, 19, 30, 35]. As in ALL, a high rate
of CNS relapse (32–50%) was observed in earlier studies
where patients did not receive specific CNS-directed
prophylaxis [19, 35]. The inclusion of i.th. therapy leads
to a substantial reduction of the CNS relapse rate [19]
which ranged from 0% to 36% in studies with CNS
prophylaxis based on i.th. therapy only [12, 19, 23, 30,
35] and from 3% to 21% in studies with i.th. therapy
and CNS irradiation [12, 23, 26, 35].
Several historical comparisons underline the potential
role of prophylactic CNS irradiation [23, 36]. In the
GMALL study, 91% of the study patients received CNS
irradiation and all of them had intensive i.th. therapy.
This approach proved to be effective since only one of
42 CR patients experienced a CNS relapse [11]. CNS irradiation
is not part of the Hyper-CVAD regimen,
which, however, included i.th. therapy and systemic
high-dose therapy. CNS involvement at relapse was seen
in three of 30 CR patients [18].
Overall published results underline the importance
of effective CNS prophylaxis in LBL and there is some
evidence that CNS irradiation is a successful approach.
It may be reasoned, however, whether CNS irradiation
could be omitted in patients with stage I-II disease in
order to avoid toxicity and treatment delays during induction
therapy.
16.6 Mediastinal Tumors
One major specific issue in T-LBL is the role of mediastinal
tumors (MedTu) as a cause for initial treatment
failure and as relapse localization. Most patients show
large MedTu at diagnosis, which in some patients even
leads to emergency situations with acute respiratory
distress and/or acute vena cava superior syndrome.