Journal of Clinical Oncology, Vol 15, 1786-1795, Copyright © 1997 by American Society of Clinical Oncology
Secondary cytogenetic changes in acute promyelocytic leukemia-- prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study
JL Slack, DC Arthur, D Lawrence, K Mrozek, RJ Mayer, FR Davey, R Tantravahi, MJ Pettenati, S Bigner, AJ Carroll, KW Rao, CA Schiffer and CD Bloomfield
Roswell Park Cancer Institute, Buffalo, NY 14263, USA. slack@dm3100.med.buffalo.edu
PURPOSE: To examine, in newly diagnosed patients with acute promyelocytic
leukemia (APL), the prognostic significance of secondary cytogenetic
changes and the relationship between such changes and the two major
promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) mRNA
types. PATIENTS AND METHODS: One hundred sixty-one patients with
t(15;17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB)
protocol 8461, a prospective study of cytogenetics in acute myeloid
leukemia (AML), were studied. Eighty of these 161 patients were treated
solely with chemotherapy and evaluated for response to treatment and
survival. PML-RAR alpha mRNA type was determined using reverse
transcriptase polymerase chain reaction (RT-PCR) in 56 patients. RESULTS:
The incidence of secondary cytogenetic abnormalities was 32%. Among 80
patients treated with chemotherapy, the presence of a secondary chromosome
abnormality was associated with longer complete remission (CR) duration
(median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS)
duration (median, 17.0 v 12.2 months; P = .03). There was no difference in
overall survival (P = .28). In a separate group of 56 patients with both
cytogenetic and molecular data, 32 had the type L PML-RAR alpha transcript
(intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had
chromosome changes in addition to t(15;17), whereas 12 of 20 patients (60%)
with the type 5 PML-RAR alpha transcript (intron 3 PML breakpoint) had
secondary cytogenetic changes (P < .001). CONCLUSION: (1) Secondary
cytogenetic changes do not confer a poor prognosis in APL patients treated
with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly
significant relationship exists between the PML-RAR alpha 5 isoform (intron
3 PML genomic breakpoint) and secondary cytogenetic changes in APL.
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