Acute Leukemias - Republican Scientific Medical Library

204 Chapter 16 · Treatment of Lymphoblastic Lymphoma in Adults
16.2 Immunophenotype
Most published studies in adults summarize patients
with LBL of B- and T-cell origin. Approximately 80%
of LBL carry T-markers which is different from ALL
with > 70% B-markers [5, 6] (Table 16.1). The reported
disease features of LBL are therefore dominated by the
T-cell subtype.
T-LBL can be separated in subtypes according to
differentiation markers similarly to T-ALL. The thymic
subtype (CD1 positive) is found most frequently. In a
childhood ALL series the incidences for early, thymic,
and mature T-ALL were 18, 71, and 10%, respectively
[7]. For adult LBL the incidence of immunologic subtypes
has not been reported so far. Whereas in T-ALL
the immunophenotype is an important prognostic marker
with inferior outcome for early and mature T-ALL
and superior outcome for thymic T-ALL [8], it’s impact
on outcome is unknown in T-LBL.
16.3 Clinical Features
LBL generally has a male preponderance (61–75%). The
majority of patients show advanced disease with stage
III-IV in 58–95%. B symptoms (16–48%) and elevated
LDH (48–84%) were present in a considerable proportion
of patients. The incidence of initial CNS involvement
is similar to ALL (0–10%) (Table 16.1).
T-LBL patients showed, compared to B-LBL younger
age [9], a higher rate of mediastinal [10] or BM [9, 10]
involvement and stage IV disease [9] whereas extranodal
involvement was more frequent in B-LBL [10].
In the so far largest study on T-LBL in adults, 89% of
the patients showed a mediastinal involvement often
(40%) associated with pleural effusion. Seventy percent
of the patients had lymph node or organ involvement
(11%) and most of them (72%) had advanced stage III/
IV disease with LDH values increased above two times
the normal in 33% of the patients [11].
In contrast to T-ALL, peripheral blood values – particularly
hemoglobin and platelet counts – were generally
near to normal in this patient cohort indicating a
potentially better BM reserve and tolerability of chemotherapy
[11].
16.4 Therapeutic Approaches
Therapeutic approaches for adult LBL included in the
past conventional protocols for NHL, intensive combination
chemotherapy protocols designed for high grade
NHL, and protocols for the treatment ALL, with or without
prophylactic cranial irradiation (as in most ALL
protocols) and with or without prophylactic or therapeutic
mediastinal irradiation. Furthermore, stem cell
transplantation (SCT) – particularly autologous SCT –
was included to a different extent in treatment strategies.
These different treatment approaches in conjunction
with differences in patient characteristics – particularly
median age and the proportion of patients with
stage III/IV disease – may explain the considerable variations
in outcome. The cumulative results of different
approaches are summarized in Table 16.2.
16.4.1 Chemotherapy Regimens Designed
for NHL
Earlier reports on conventional NHL protocols such as
CHOP-based regimens yielded relatively low complete
remission (CR) rates (53–71%) and rates for disease-free
survival (DFS) (23–53%) [14, 16, 19–21] (Table 16.2).
Improved results for adult patients with LBL were
later reported for a modified CHOP regimen with additional
application of asparaginase, CNS prophylaxis,
and maintenance therapy. With this regimen, known
as “Stanford/NCOG,” CR rates of 79–100% and DFS
rates of 23–56% were achieved [22–25]. Thus there was
growing evidence that intensified and prolonged chemotherapy
together with CNS prophylaxis is beneficial
in LBL.
With more intensive NHL regimens, designed for
childhood NHL such as the LSA2-L2 or LNH-84 regimen,
the CR rates were higher (73–84%) but not the
DFS rates (35–44%) [14, 26]. Two studies which both included
SCT yielded a more favorable DFS of 75% [27] or
overall survival of 85% in T-LBL [28].
16.4.2 Chemotherapy Regimens Designed
for ALL
The largest experience on treatment of adult LBL is
available from ALL-type regimens (Table 16.3). In earlier
studies at the Memorial Sloan Kettering Cancer