Comparison of central nervous system prophylaxis with cranial radiation and
intrathecal methotrexate versus intrathecal methotrexate alone in acute
lymphoblastic leukemia
FS Muriel, E Svarch, S Pavlovsky, M Eppinger-Helft, J Braier, B Vergara, G Garay, R Kvicala, JM Divito, R Failace, E Dibar and E Jimenez
In acute lymphoblastic leukemia (ALL), central nervous system (CNS)
prophylaxis with cranial irradiation plus 5 doses of intrathecal
methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%.
However, increased evidence of CNS delayed toxicity started to be
recognized as CT scan abnormalities and neuropsychologic alterations,
mainly in children. Two questions were analyzed in the present report: (1)
Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX- DMT)
decrease the incidence of CNS relapse in patients treated early in
remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t.
MTX-DMT given during induction and maintenance equally as effective as
cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to
answer the first question. Incidence of primary CNS relapse in i.t.
MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of
135 patients) and was 11% (17 of 150) in the untreated group. In patients
with a WBC count greater than 50,000, it was 16% (6/37) in the treated
group and 19% (6/31) in the control group. No difference was observed
according to treatment in both prognostic groups. Patients in this study
were retrospectively compared with a consecutive protocol in which patients
received 3 doses of i.t. MTX-DMT alone during induction plus 3 doses weekly
during the first month of remission and every 3 mo thereafter. The
incidence of primary CNS leukemia at 60 mo in patients with a WBC count
less than 50,000 was 20% in the irradiated group and 32% in the group with
i.t. MTX-DMT alone. This difference was not significant. However, the
relapse-free survival at 60 mo was 26% and 41%, respectively, (p less than
0.0005). The incidence of primary CNS relapse in patients with a WBC count
more than 50,000 at 48 mo was 28% in the irradiated group and 42% in the
nonirradiated group. The difference was not significant. The duration of
complete remission was similar, remaining at 15% and 16% of patients
disease-free at 48 mo, respectively. We conclude that (A) after cranial
irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t.
MTX-DMT is not of further benefit in preventing CNS relapse; (B) the use of
i.t. MTX-DMT alone compares similarly with cranial irradiation plus i.t.
MTX-DMT in the incidence of CNS relapse; and (C) relapse-free survival and
survival in patients with a WBC count less than 50,000 were significantly
longer in those without cranial irradiation.
Volume 62,
Issue 2,
pp. 241-250,
08/01/1983
Copyright © 1983 by The American Society of Hematology
