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 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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134Jurcic -
347Nimer -
499Scheinberg -
57DeBlasio -
175
Warrell
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