Acute Leukemias - Republican Scientific Medical Library

a 21.6 · CNS Treatment 269
with this form of ALL have CNS leukemia at the time of
diagnosis [34, 35, 68]. Hoelzer et al. [34] used IT and cranial
irradiation and the rate of isolated CNS relapse decreased
from 20 to 0% with the introduction of triple IT
(methotrexate, cytarabine, and dexamethasone). At MD
Anderson Cancer Center (MDACC) [35] the HyperCVAD
regimen includes HDCT (methotrexate, cytarabine,
dexamethasone, cyclophosphamide, doxorubicin, and
vincristine) together with eight alternating IT doses of
methotrexate and cytarabine for a total of 16 doses.
No isolated CNS relapses were observed among 26 patients
treated with this regimen.
In conclusion, CNS prophylaxis in adult ALL can be
achieved without cranial irradiation. For patients with
low-risk for CNS disease, prophylaxis with HDST alone
and an abbreviated course of IT (e.g., 4–6 doses) may
provide effective prophylaxis. For those patients with
high-risk for CNS disease, early HDST and IT virtually
eliminates the risk of CNS relapse. The risk-oriented
approach is an excellent tool to minimize risk and optimize
efficacy.
21.6 CNS Treatment
The treatment of patients who develop CNS leukemia
has unfortunately not been standardized, and there is
little information about the optimal management of
adult patients. There are two different scenarios of occurrence
of CNS leukemia: at the time of diagnosis
and CNS relapse. Patients, who present at the time of diagnosis
with CNS involvement, are treated with a more
intensive IT regimen than the one used for prophylaxis.
This may also include cranial irradiation. Kantarjian et
al. [67] treated patients with CNS leukemia with twiceweekly
IT doses, alternating methotrexate and cytarabine,
until the CSF had no more identifiable leukemia
cells in two consecutive determinations. Patients then
followed the standard IT prophylaxis schedule consisting
of an IT methotrexate and cytarabine dose with each
of the eight courses of chemotherapy. CNS irradiation
was not incorporated into this treatment program, except
for those patients with cranial-nerve root involvement
who received 2400 to 3000 rads of radiation in
10–12 fractions directed to the base of the skull or to
the whole brain. Using this approach, the presence of
CNS leukemia at the time of diagnosis did not have
an adverse impact on outcome, suggesting that the
strategy was effective.
Another approach used 3000 rads cranial irradiation
and IT for patients with CNS leukemia at the time
of induction [69, 70]. Linker et al. [70] treated 109 adult
patients with ALL excluding patients who were more
than 50 years old, and Burkitt’s leukemia. CNS prophylaxis
was initiated within 1 week of the achievement of
CR. Eighteen hundred rads of cranial irradiation were
delivered in 10 fractions over 12–14 days. Six weekly
doses of 12 mg of IT methotrexate were administered
by lumbar puncture. Patients with CNS involvement at
diagnosis began their weekly IT methotrexate during
the induction chemotherapy and received 10 weekly
doses. Thereafter, these high-risk patients received IT
methotrexate monthly during the first year of therapy
and their dose of cranial irradiation was increased to
2,800 rads. This study accrued 109 patients who ranged
in age from 16 to 49 years, with a median age of
25 years. Seven patients presented with CNS disease at
diagnosis. The results of this therapeutic approach
showed that neither sex, WBC count, or the presence
of CNS disease were predictive of outcome. Patients
with no leukemia evidence on day 14 of induction (receiving
three doses of daunorubicin) had projected
CCR rate of 51% ± 8% compared with 40%±8% for patients
achieving remission after four doses of daunorubicin
[70].
CNS disease is present at the time of diagnosis more
frequently among patients with mature B-cell ALL.
Good results have been obtained with a regimen using
intensive IT and high-dose systemic chemotherapy [34,
35]. In one recent study, 26 adults with newly diagnosed
mature B-cell ALL received Hyper-CVAD and CNS
prophylaxis alternated IT methotrexate and cytarabine
on days 2 and 7 of each course for a total eight courses
[35]. Their median age was 58 years (range 17 to
79 years), and 46% were ³60 years. Complete hematologic
remission (CR) was obtained in 21 patients (81%).
There were five induction deaths (19%). Eleven (42%)
patients had CNS disease at the time of diagnosis and
had a similar outcome. The presence of CNS disease
at diagnosis was not associated with a lower probability
of remission or survival. No isolated CNS relapses were
observed.
CNS relapse can occur in three clinical settings: isolated
CNS relapse, concomitant bone marrow (BM) and
CNS relapse, and CNS relapse after BM recurrence. Over
80% of children with isolated CNS recurrence will die or
will have a subsequent recurrence if there is no change
in their systemic therapy [71]. A similar outcome can be