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Prognostic significance of minimal residual disease detection and PML/RAR-alpha isoform type: long-term follow-up in acute promyelocytic leukemia
Author(s): Jurcic JG, Nimer SD, Scheinberg DA, DeBlasio T, Warrell RP, Miller WH
Source: BLOOD    Volume: 98    Issue: 9    Pages: 2651-2656    Published: NOV 1 2001  
Times Cited: 43     References: 49     
Abstract: The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PMU RAR-alpha 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-alpha 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. (C) 2001 by The American Society of Hematology.
Document Type: Article
Language: English
Reprint Address: Jurcic, JG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA
Addresses:
1. Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA
2. Mem Sloan Kettering Canc Ctr, Dept Med, Hematol Serv, New York, NY 10021 USA
3. Mem Sloan Kettering Canc Ctr, Dept Med, Dev Chemotherapy Serv, New York, NY 10021 USA
4. Cornell Univ, Weill Med Coll, New York, NY USA
5. McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2 Canada
Publisher: AMER SOC HEMATOLOGY, 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
Subject Category: Hematology
IDS Number: 487CK
ISSN: 0006-4971
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