Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter "AIDA" trial. GIMEMA-AIEOP Multicenter "AIDA" Trial.
Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter "AIDA" trial. GIMEMA-AIEOP Multicenter "AIDA" Trial.
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发表时间：
1998
期刊：
影响因子：
20.3
通讯作者：
D. Diverio;V. Rossi;G. Avvisati;S. De Santis;A. Pistilli;F. Pane;G. Saglio;G. Martinelli;M. Petti;A. Santoro;P. Pelicci;F. Mandelli;A. Biondi;F. Lo Coco
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作者：
D. Diverio;V. Rossi;G. Avvisati;S. De Santis;A. Pistilli;F. Pane;G. Saglio;G. Martinelli;M. Petti;A. Santoro;P. Pelicci;F. Mandelli;A. Biondi;F. Lo Coco
虽然大多数急性早幼粒细胞白血病（APL）患者通过全反式维甲酸（ATRA）和化疗（CHT）联合治疗可能治愈，但相当大比例（约30%）将在随访期间复发。使用逆转录-聚合酶链反应（RT-PCR）对特定PML/RAR α融合基因进行的回顾性分子监测研究表明，阳性检测通常先于血液学复发的发生。自1993年以来，在诊断时和随访期间的预定时间间隔，对163例PML/RAR α + APL患者的骨髓（BM）样本进行了前瞻性RT-PCR分析，这些患者入组了多中心Gruppo Italiano Malattie Ematologiche Malatne dell' Adulto（GIMEMA）试验AIDA（全反式维甲酸加伊达洛酮）。治疗包括全反式维甲酸和伊达洛酮诱导，然后是三个多疗程的巩固化疗。通过系列稀释实验评估，PML/RAR α RT-PCR检测的灵敏度水平为10（-4）。所有患者均处于血液学缓解期，并在巩固治疗结束时进行PCR-检测。在此后转为PCR阳性的21例患者中，20例在首次PCR+结果后中位3个月（范围，1至14）时发生血液学复发。这21例（81%）PCR+转换中有17例在合并后的前6个月内记录。在142例巩固治疗后持续检测PCR- in ≥ 2次的患者中，8例出现血液学复发，134例在巩固治疗后中位随访18个月（范围6 - 38）后仍保持完全缓解（CR）。使用时间依赖性考克斯模型，转换为PCR+的患者血液学复发的相对风险为31.8（置信限95%，12.9至78.3）。我们的研究结果表明，缓解期PML/RAR α PCR阳性转化高度预测随后的血液学复发，并强调了APL巩固后早期严格分子监测的预后价值。作为本研究的结果，现在预计参加GIEMA试验AIDA的患者在分子复发时会接受挽救治疗，分子复发定义为随访期间两次连续BM采样中PCR阳性的转化。
Although the majority of patients with acute promyelocytic leukemia (APL) are potentially cured by treatments combining all-trans retinoic acid (ATRA) and chemotherapy (CHT), a sizable proportion (around 30%) will relapse during follow-up. Retrospective molecular monitoring studies using reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific PML/RARalpha fusion gene, have shown that a positive test usually precedes the occurrence of hematologic relapse. Prospective RT-PCR analyses were performed since 1993 at diagnosis and at preestablished time intervals during follow-up in bone marrow (BM) samples of 163 patients with PML/RARalpha+ APL enrolled in the multicenter Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) trial AIDA (All-trans retinoic acid plus Idarubicin). Treatment consisted of ATRA and idarubicin for induction followed by three polychemotherapy courses as consolidation. The sensitivity level of the RT-PCR assay for PML/RARalpha, 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%) PCR+ conversions were recorded within the first 6 months postconsolidation. Of 142 who tested persistently PCR- in >/=2 tests 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 relative 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/RARalpha during remission is highly predictive of subsequent hematologic relapse and highlight the prognostic value of stringent molecular monitoring during the early postconsolidation phase in APL. As a result of the present study, salvage treatment in patients enrolled in the GIMEMA trial AIDA is now anticipated at the time of molecular relapse, defined as the conversion to PCR positivity in two successive BM samplings during follow-up.