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

Purpose: To examine, in newly diagnosed patients with acute promyelocy tic leukemia (APL), the prognostic significance of secondary cytogenet ic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) m RNA 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 le ukemia (AML), were studied, Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and s urvival. PML-RAR alpha mRNA type wets determined using reverse transcr iptase polymerase chain reaction (RT-PCR) in 56 patients, Results: The incidence of secondary cytogenetic abnormalities was 32%. Among 80 pa tients treated with chemotherapy, the presence of a secondary chromoso me abnormality was associated with longer complete remission (CR) dura tion (median, 29.9 v 15.7 months; P = .03) and longer event free survi val (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 p atients with both cytogenetic and molecular date, 32 had the type L PM L-RAR alpha transcript (intron 6 PML breakpoint). OF these 32 patients , four (12.5%) had chromosome changes in addition to t(15; 17), wherea s 12 of 20 patients (60%) with the type S PML-RAR alpha transcript (in tron 3 PML breakpoint) had secondary cytogenetic changes (P < .001),Co nclusion: (1) secondary cytogenetic changes do not confer a poor progn osis in APL patients treated with anthracycline/cytarabine (Ara-C)-bas ed chemotherapy; and (2) A highly significant relationship exists betw een the PML-RAR alpha S isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL. (C) 1997 by American Society of Clinical Oncology.