EARLY DETECTION OF RELAPSE BY PROSPECTIVE REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION ANALYSIS OF THE PML RAR-ALPHA FUSION GENE IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA ENROLLED IN THE GIMEMA-AIEOP MULTICENTER AIDA TRIAL/

Citation
D. Diverio et al., EARLY DETECTION OF RELAPSE BY PROSPECTIVE REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION ANALYSIS OF THE PML RAR-ALPHA FUSION GENE IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA ENROLLED IN THE GIMEMA-AIEOP MULTICENTER AIDA TRIAL/, Blood, 92(3), 1998, pp. 784-789
Citations number
28
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
92
Issue
3
Year of publication
1998
Pages
784 - 789
Database
ISI
SICI code
0006-4971(1998)92:3<784:EDORBP>2.0.ZU;2-2
Abstract
Although the majority of patients with acute promyelocytic leukemia (A PL) are potentially cured by treatments combining all-trans retinoic a cid (ATRA) and chemotherapy (CHT), a sizable proportion (around 30%) w ill relapse during follow-up. Retrospective molecular monitoring studi es using reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific PML/RAR alpha fusion gene, have shown that a positive tes t usually precedes the occurrence of hematologic relapse. Prospective WT-PCR analyses were performed since 1993 at diagnosis and at preestab lished time intervals during follow-up in bone marrow (BM) samples of 163 patients with PML/RAR alpha(+) APL enrolled in the multicenter Gru ppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) trial AIDA (All-trans retinoic acid plus Idarubicin). Treatment consisted o f ATRA and idarubicin for induction followed by three polychemotherapy courses as consolidation. The sensitivity level of the RT-PCR assay f or PML/RAR alpha, as assessed by serial dilution experiments, was 10(- 4). All patients were in hematologic remission and tested PCR- at the end of consolidation. of 21 who converted to PCR-positive thereafter, 20 underwent hematologic relapse at a median time of 3 months (range, 1 to 14) from the first PCR+ result. seventeen of these 21 (81%) PCRconversions were recorded within the first 6 months postconsolidation. Of 142 who tested persistently PCR- in greater than or equal to 2 tes ts after consolidation, 8 had hematologic relapse and 134 remained in complete remission (CR) after a median follow-up of 18 months (range, 6 to 38) postconsolidation. Using a time-dependent Cox model, the rela tive risk of hematologic relapse of patients who converted to PCR+ was 31.8 (confidence limits 95%, 12.9 to 78.3). our results indicate that conversion to PCR positivity for PML/RAR alpha during remission is hi ghly predictive of subsequent hematologic relapse and highlight the pr ognostic value of stringent molecular monitoring during the early post consolidation phase in APL. As a result of the present study salvage t reatment in patients enrolled in the GIMEMA trial AIDA is now anticipa ted at the time of molecular relapse, defined as the conversion to PCR positivity in two successive BM samplings during follow-up. (C) 1998 by The American Society of Hematology.