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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2651-2656
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Prognostic significance of minimal residual disease detection and
PML/RAR- isoform type: long-term follow-up in acute
promyelocytic leukemia
Joseph G. Jurcic,
Stephen
D. Nimer,
David A. Scheinberg,
Tony DeBlasio,
Raymond P. Warrell Jr, and
Wilson H. Miller Jr
From the Leukemia, Hematology, and Developmental
Chemotherapy Services, Department of Medicine, Memorial Sloan-Kettering
Cancer Center, and the Weill Medical College of Cornell University, New
York, NY, and the Lady Davis Institute of the Jewish General Hospital,
McGill University, Montreal, QC, Canada.
The t(15;17) translocation in acute promyelocytic leukemia (APL)
yields a PML/RAR- fusion messenger RNA species that can be
detected by reverse transcription-polymerase chain reaction (RT-PCR)
amplification. Breakpoints within intron 3 of PML produce a short
PML/RAR- isoform, whereas breakpoints within intron 6 result in a
longer form. Using RT-PCR, serial evaluations were performed on the
bone marrow of 82 patients with APL (median follow-up, > 63 months)
who received retinoic acid (RA) induction followed by postremission
treatment with chemotherapy, RA, and biologic agents. Sixty-four
patients attained a clinical complete remission and had at least 2 RT-PCR assays performed after completing therapy. Forty of 47 patients
(85%) with newly diagnosed APL who were induced using RA had residual
disease detectable 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 or more positive results had a
relapse. Among 63 newly diagnosed patients, those 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
associated with long-term remissions. Conversely, a confirmed positive
test is highly predictive of relapse.
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