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The value of high-dose systemic chemotherapy and intrathecal therapy for
central nervous system prophylaxis in different risk groups of adult acute
lymphoblastic leukemia
J Cortes, SM O'Brien, S Pierce, MJ Keating, EJ Freireich and HM Kantarjian
Department of Hematology, University of Texas M.D. Anderson Cancer Center,
Houston 77030, USA.
Although central nervous system (CNS) leukemic relapse is frequent in adult
acute lymphocytic leukemia (ALL), the need for prophylaxis in different
risk groups for CNS relapse, the value of high-dose systemic and
intrathecal (IT) chemotherapy, and the timing of prophylaxis are not well
defined. This analysis was conducted to investigate these questions and to
assess the value of a risk-oriented CNS prophylaxis approach. We analyzed
the incidence of CNS leukemia after initiation of therapy in patients
treated on 4 consecutive trials for adult ALL including different CNS
prophylactic modalities. The treatment groups included (1) the program
preceeding the vincristine-Adriamycin- dexamethasone (VAD) regimen, with no
CNS prophylaxis; (2) the VAD regimen with prophylaxis using high-dose
systemic chemotherapy; (3) the modified VAD program with high-dose systemic
chemotherapy to all patients and IT chemotherapy for high-risk patients
after achieving complete remission; and (4) the hyperCVAD program with
early high-dose systemic and IT chemotherapy starting during induction to
all patients, with more IT injections (16IT) administered to the high-risk
group for CNS relapse compared with the low-risk group (4IT). A total of
391 patients were included, 73 of whom were treated with preVAD, 112 with
VAD, 114 with modified VAD, and 92 with hyperCVAD. The overall CNS relapse
rates were 31%, 18%, 17%, and 3%, respectively for the 4 groups (P <
.001). For the high-risk group for CNS relapse, they were 42%, 26%, 20%,
and 2%, respectively (P < .001). The differences in CNS relapse rates in
the low-risk group were not statistically significant. At 3 years, the
overall CNS leukemia event-free rates were 48%, 76%, and 98%, respectively
(P < .001). In the high-risk group, the CNS event- free rates were 38%,
66%, 75%, and 98%, respectively (P < .001); however, there was no
difference in the low-risk group. We conclude that (1) high-dose systemic
chemotherapy is a useful prophylactic measure; (2) early IT chemotherapy is
necessary to reduce the incidence of CNS leukemia overall and in the
high-risk group; and (3) a risk- oriented approach is appropriate to tailor
the intensity of CNS prophylaxis.
Volume 86,
Issue 6,
pp. 2091-2097,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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