Acute Leukemias - Republican Scientific Medical Library

198 Chapter 15 · Burkitt’s Acute Lymphoblastic Leukemia (L 3ALL) in Adults
served with this protocol, which was then modified [14].
The second group of patients received only six intrathecal
chemotherapy injections and radiotherapy was given
later in the course of the protocol (after chemotherapy).
Neurological toxicity was significantly reduced
with this less-intensive CNS prophylaxis. CNS relapses
and overall treatment efficacy were not modified [13,
14].
Kantarjian et al. [41] reported results of a protocol
alternating eight cycles of hyper-CVAD (with fractionated
CPM and high dose VAD) and HD MTX (3 g/m 2 )
combined to HD AraC (3 g/m 2 ) and overall 16 intrathecal
injections in 11 cases of L 3ALL. Eight achieved
CR, but the 5-year survival rate was only 33%. Causes
of failure were not detailed. When all mature B cell
ALL cases were considered, only 29% of the cases
could be cured.
The combination of Rituximab and “Burkitt-tailored”
chemotherapy has recently been tested in Burkitt
and Burkitt-like leukemia and lymphoma [42, 43]. Preliminary
results in HIV-positive and HIV-negative patients
showed a high response rate in patients with Burkitt
leukemia/lymphoma. Patients with ALL have not
been evaluated separately and it remains to be seen
whether the favorable response rate observed with these
new combinations will translate into improved survival.
Finally, like in children, almost all relapses in adult
disseminated BL and L 3ALL occur within 1 year of diagnosis,
and prolonged maintenance treatment therefore
is also unnecessary in those patients.
15.5 Prognostic Factors in Adult L3ALL
The considerable improvement that has been observed
in the outcome of L 3ALL in adults makes delineation
of the patient population still at high risk of failure with
those regimens particularly important. In the two published
series with sufficiently large numbers of L 3ALL
patients treated “optimally,” patients with poor performance
status at diagnosis [35] and older patients [9]
had somewhat lower CR rates. Patients with CNS involvement
or other extramedullary disease had poorer
outcome in the study of Hoelzer et al. [9]. In the French
SFOP 84 trial, CNS involvement was also a poor prognostic
factor. However, it was no more a prognostic factor
in the SFOP 86 trial, which incorporated higher dose
MTX (8 g/m 2 ), high-dose Ara C 3 g/m 2 , and cranial irradiation
at 24 Gy [28].
Hoelzer, et al. [9] also found high WBC counts
(> 50´10 9 /l) and hemoglobin < 8 g/dl to be associated
with a higher risk of relapse whereas LDH levels had
borderline significance. No other biological prognostic
with prognostic importance clearly exists in L 3ALL.
We found in particular that p53 mutations had no prognostic
value in BL or L3ALL, contrary to most other
hematological malignancies [44].
Recently, additional cytogenetic abnormalities to the
classical c-myc rearrangement were found to be associated
with a poor outcome [45–46]. The prognostic value
of additional cytogenetic abnormalities needs to be
validated on more adult cases but represent new biological
prognostic factors of special interest. Abnormalities
in 1q and 7q detected by CGH analysis could be associated
with a poor outcome in patients with Burkitt lymphoma
or L 3ALL [16].
15.6 Treatment of Resistant and Relapsing
Disease
Experience in the treatment of childhood BL has suggested
that salvage chemotherapy, followed by intensification
with autologous SCT could salvage about 40% of
relapsing patients and patients who achieved only PR
with first-line therapy. Drugs used for salvage chemotherapy
included in particular HD MTX and high-dose
AraC, and/or etoposide and cisplatin.
This relatively high incidence of durable salvage,
however, was mostly reported in selected series of patients
that often had received less than optimal first-line
therapy, and who were able to reach autologous SCT. It
was less clear if similar efficacy could be observed in
unselected patients who had only partial response or relapsed
after first-line treatment using recent intensive
multiagent protocols. For example, Philip et al. [47] reported
the outcome of 27 patients with BL who had relapsed
after the SFOP 84 trial (14% of the patients who
had achieved CR). Three of them had early death; 15 of
the remaining 24 patients had at least partial response
to salvage regimens (VP16 and HD AraC, VP16 and cisplatin
or MIME) and could be autografted. Four of them
had prolonged survival, whereas none of the patients
who could not be autografted survived. Thus, only four
of the 27 patients who relapsed could be durably salvaged.
In the case of adult L3ALL initially treated with conventional
ALL protocols, reports suggest that virtually