Iacobucci Ilaria, Saglio Giuseppe, Rosti Gianantonio, Testoni Nicoletta, Pane Fabrizio, Amabile Marilina, Poerio Angela, Soverini Simona, Bassi Simona, Cilloni Daniela, Bassan Renato, Breccia Massimo, Lauria Francesco, Izzo Barbara, Merante Serena, Frassoni Francesco, Paolini Stefania, Montefusco Enrico, Baccarani Michele, Martinelli Giovanni
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Bologna, Italy.
Clin Cancer Res. 2006 May 15;12(10):3037-42. doi: 10.1158/1078-0432.CCR-05-2574.
Most patients with chronic-phase chronic myeloid leukemia (CML) who receive imatinib achieve a complete cytogenetic remission (CCgR) and low levels of BCR-ABL transcripts. CCgR is durable in the majority of patients but relapse occurs in a subset.
To determine the potential of quantitative reverse transcription-PCR of BCR-ABL to predict cytogenetic relapse, we serially monitored residual disease in 97 CML patients with an imatinib-induced CCgR. Patients with late chronic phase CML after IFN-alpha failure were treated with imatinib (400 mg daily).
During the imatinib median follow-up time of 36 months (range, 12-54 months), disease monitoring occurred by cytogenetics and quantitative PCR. Twenty percent of patients experienced cytogenetic relapse at a median of 18 months after CCgR and a median of 24 months after starting imatinib. None of the possible prognostic factors studied in univariate and multivariate analyses seemed to predict for loss of cytogenetic response but the reduction of BCR-ABL transcript levels at the time of CCgR is an important prognostic factor.
In our study, we showed not only that achieving a major molecular remission at 12 months is predictive of a durable cytogenetic remission but also that patients who achieved a major molecular remission (expressed both as the BCR-ABL/beta2 microglobulin ratio % <0.0005 and as a 3-log reduction from median baseline value) already at the time of first achieving a CCgR have significantly longer cytogenetic remission durations than those without this magnitude of molecular response (P < 0.05).
大多数接受伊马替尼治疗的慢性期慢性髓性白血病（CML）患者可实现完全细胞遗传学缓解（CCgR）并使BCR-ABL转录水平降低。CCgR在大多数患者中是持久的，但仍有一部分患者会复发。
为了确定BCR-ABL定量逆转录PCR预测细胞遗传学复发的潜力，我们对97例伊马替尼诱导实现CCgR的CML患者的残留疾病进行了连续监测。干扰素-α治疗失败后的晚期慢性期CML患者接受伊马替尼治疗（每日400mg）。
在伊马替尼中位随访时间36个月（范围12 - 54个月）期间，通过细胞遗传学和定量PCR进行疾病监测。20%的患者在CCgR后中位18个月、开始伊马替尼治疗后中位24个月时出现细胞遗传学复发。单因素和多因素分析中研究的所有可能的预后因素似乎均不能预测细胞遗传学反应的丧失，但CCgR时BCR-ABL转录水平的降低是一个重要的预后因素。
在我们的研究中，我们不仅表明在12个月时实现主要分子缓解可预测持久的细胞遗传学缓解，而且还表明在首次实现CCgR时就已实现主要分子缓解（以BCR-ABL/β2微球蛋白比率%<0.0005以及相对于中位基线值降低3个对数表示）的患者，其细胞遗传学缓解持续时间显著长于未达到这种分子反应程度的患者（P<0.05）。
