Journal of Clinical Oncology, Vol 11, 209-217, Copyright © 1993 by American Society of Clinical Oncology
Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide
NJ Winick, RW McKenna, JJ Shuster, NR Schneider, MJ Borowitz, WP Bowman, D Jacaruso, BA Kamen and GR Buchanan
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
PURPOSE: To describe the occurrence of secondary acute myeloid leukemia
(AML) in children with acute lymphoblastic leukemia (ALL) treated with
etoposide (VP-16). PATIENTS AND METHODS: Two hundred five consecutive
children with early B-lineage ALL were treated according to the Dallas/Fort
Worth (DFW) protocol between January 1986 and July 1, 1991. Therapy
included a four-drug induction followed by consolidation and continuation
phases of nightly oral mercaptopurine (6-MP) and repetitive courses of
divided-dose oral methotrexate (dMTX) and asparaginase (L-asp). Three doses
of VP-16 and cytarabine (Ara-C) were given during consolidation and later,
during continuation, two doses were given 3 to 4 days apart, every 9 weeks.
Intrathecal (IT) chemotherapy was given throughout the treatment period.
RESULTS: Two hundred three of the 205 patients entered remission. Only
eight of these 203 children have had a bone marrow relapse (ALL). However,
10 other children have developed secondary AML 23 to 68 months following
the diagnosis of ALL. Overall event-free survival (EFS) at 4 years is 79.3%
+/- 5.1%, with a risk of secondary AML at 4 years of 5.9% +/- 3.2%.
CONCLUSION: This experience provides strong evidence for a link between
epipodophyllotoxin therapy and secondary AML since none of these children
received alkylating agent therapy or irradiation. This serious complication
raises concern as to the appropriate use of epipodophyllotoxins in the
treatment of childhood ALL.
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