Prognostic significance of minimal residual disease detection and PML/RAR-alpha isoform type: long-term follow-up in acute promyelocytic leukemia

The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a P MU RAR-alpha fusion messenger RNA species that can be detected by reverse t ranscription-polymerase chain reaction (RT PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-alpha isoform, whereas break points within intron 6 result in a longer form. Using RT-PCR, serial evalua tions were performed on the bone marrow of 82 patients with APL (median fol low-up, > 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. Sixty-f our patients attained a clinical complete remission and had at least 2 RT P CR assays performed after completing therapy. Forty of 47 patients (85%) wi th newly diagnosed APL who were induced using RA had residual disease detec table by RT-PCR before additional therapy. After 3 cycles of consolidation therapy, residual disease was found in only 4 of 40 evaluable patients (10% ). Among newly diagnosed patients who had 2 or more negative RT-PCR assays, only 3 of 41 (7%) had a relapse, whereas all 4 patients (100%) who had 2 o r more positive results had a relapse. Among 63 newly diagnosed patients, t hose who expressed the short isoform appeared to have shorter disease-free and overall survival durations than patients who expressed the long isoform . These data indicate that 2 or more negative RT PCR assays on bone marrow, performed at least 1 month apart after completing therapy, are strongly as sociated with long-term remissions. Conversely, a confirmed positive test i s highly predictive of relapse. (C) 2001 by The American Society of Hematol ogy.