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.

Abstract

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.

• Authors: J L Slack, D C Arthur, D Lawrence, K Mrózek, R J Mayer, F R Davey, R Tantravahi, M J Pettenati, S Bigner, A J Carroll, K W Rao, C A Schiffer, C D Bloomfield
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 15 Issue 5 Pg. 1786-95 (May 1997) ISSN: 0732-183X [Print] United States
• PMID: 9164186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RARA protein, human
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• Cytarabine
• Daunorubicin

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chromosome Aberrations (genetics)
• Chromosomes, Human, Pair 15
• Chromosomes, Human, Pair 17
• Chromosomes, Human, Pair 8
• Cytarabine (administration & dosage)
• Daunorubicin (administration & dosage)
• Female
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, genetics)
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Receptors, Retinoic Acid (genetics)
• Retinoic Acid Receptor alpha
• Translocation, Genetic