Martín G, Barragán E, Bolufer P, Chillón C, García-Sanz R, Gómez T, Brunet S, González M, Sanz M A
Servicio de Hematología, Hospital Universitario La Fe, Av. Campanar 21, 46009 Valencia, Spain.
Haematologica. 2000 Jul;85(7):699-703.
The detection of CBFbeta/MYH11 transcripts by RT-PCR has became a valuable and widely used technique in the accurate cytogenetic and molecular classification of acute myeloid leukemia (AML), but the clinical value of RT-PCR for monitoring minimal residual disease (MRD) during follow-up remains unclear.
We analyzed the factors predicting relapse and the value of MRD monitoring by RT-PCR in a series of 16 patients with CBFb/MYH11-positive AML (15 M4Eo; 1 M4). Fifteen were newly diagnosed cases (CR1) and one was studied after first relapse (CR2). Eight patients had clinical relapse at 6 to 19 months from the achievement of CR.
Presenting WBC count had a significant prognostic influence on disease-free survival (p=0.001). All four patients with a WBC count >100x10(9)/L relapsed, while only four additional relapses occurred among the eleven patients who had an initial WBC count below 100x10(9)/L. With regards to molecular monitoring, all relapses but one occurred in patients who showed persistent RT-PCR positivity during hematologic remission. By contrast, conversion to a repeatedly PCR-negative status was observed in the seven patients who remained in CR1 after a median follow-up of 48 months (range 31-79 months), as well as in the transplanted patient who was monitored in CR2. In these patients a PCR-positivity could be detected up to 24 months after diagnosis (median time to conversion to PCR-negative: 8 months).
In conclusion, marked hyperleukocytosis (>100x10(9)/L) confers poor prognosis to the patient with CBFbeta/MYH11-positive AML. In addition, slow kinetics of molecular remission was observed in this subset of AML, but the CBFb/MYH11 fusion transcript is no longer detectable in long-term survivors, indicating that molecular remission is an important therapeutic goal.
通过逆转录聚合酶链反应（RT-PCR）检测CBFβ/MYH11转录本已成为急性髓系白血病（AML）精确细胞遗传学和分子分类中一项有价值且广泛应用的技术，但RT-PCR在随访期间监测微小残留病（MRD）的临床价值仍不明确。
我们分析了16例CBFb/MYH11阳性AML患者（15例M4Eo；1例M4）中预测复发的因素以及RT-PCR监测MRD的价值。15例为新诊断病例（CR1），1例为首次复发后研究（CR2）。8例患者在达到CR后6至19个月出现临床复发。
初诊时白细胞计数对无病生存有显著预后影响（p = 0.001）。所有4例白细胞计数>100×10⁹/L的患者均复发，而最初白细胞计数低于100×10⁹/L的11例患者中仅另外4例复发。关于分子监测，除1例复发外，所有复发均发生在血液学缓解期间RT-PCR持续阳性的患者中。相比之下，在中位随访48个月（范围31 - 79个月）后仍处于CR1的7例患者以及在CR2中接受监测的移植患者中，观察到转为反复PCR阴性状态。在这些患者中，诊断后长达24个月可检测到PCR阳性（转为PCR阴性的中位时间：8个月）。
总之，明显的高白细胞血症（>100×10⁹/L）使CBFβ/MYH11阳性AML患者预后不良。此外，在这一亚组AML中观察到分子缓解动力学缓慢，但长期存活者中不再可检测到CBFb/MYH11融合转录本，表明分子缓解是一个重要的治疗目标。
