Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type: Long-term follow-up in acute promyelocytic leukemia Journal Article

Authors: Jurcic, J. G.; Nimer, S. D.; Scheinberg, D. A.; Deblasio, T.; Warrell, R. P. Jr; Miller, W. H. Jr
Article Title: Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type: Long-term follow-up in acute promyelocytic leukemia
Abstract: The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-α 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-α 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. © 2001 by The American Society of Hematology.
Keywords: adolescent; adult; cancer survival; child; aged; aged, 80 and over; middle aged; survival analysis; major clinical study; cancer recurrence; cytarabine; follow up; follow-up studies; prospective studies; reverse transcription polymerase chain reaction; gene expression; bone marrow; neoplasm proteins; tumor markers, biological; recurrence; cancer therapy; dna strand breakage; leukemia, promyelocytic, acute; iodine 131; messenger rna; minimal residual disease; neoplasm, residual; reverse transcriptase polymerase chain reaction; rna, messenger; promyelocytic leukemia; oncogene proteins, fusion; predictive value of tests; remission induction; alitretinoin; idarubicin; retinoic acid; protein isoforms; retinoic acid receptor; receptor subtype; monoclonal antibody m 195; humans; prognosis; human; priority journal; article
Journal Title: Blood
Volume: 98
Issue: 9
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2001-11-01
Start Page: 2651
End Page: 2656
Language: English
DOI: 10.1182/blood.V98.9.2651
PUBMED: 11675334
PROVIDER: scopus
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Joseph G Jurcic
    130 Jurcic
  2. Stephen D Nimer
    347 Nimer
  3. Raymond P Warrell
    131 Warrell