Yoon Jae-Ho, Kim Hee-Je, Kwak Dae-Hun, Park Sung-Soo, Jeon Young-Woo, Lee Sung-Eun, Cho Byung-Sik, Eom Ki-Seong, Kim Yoo-Jin, Lee Seok, Min Chang-Ki, Cho Seok-Goo, Kim Dong-Wook, Lee Jong Wook, Min Woo-Sung
Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Korea.
J Hematol Oncol. 2017 Jan 23;10(1):30. doi: 10.1186/s13045-017-0404-4.
Wilms' tumor gene 1 (WT1) expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL) and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen) for WT1 monitoring. High WT1 expression (>120 copies/10 ABL1) after consolidation and at early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40) showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001) and inferior disease free survival (62.8 vs. 91.4%, P < 0.001). Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001) and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001) were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention.
Clinical Research Information Service (CRIS), KCT0002079.
威尔姆斯瘤基因1（WT1）表达是急性髓系白血病复发的一个众所周知的预测指标。我们在治疗过程中监测WT1的下降情况，以确定其作为急性早幼粒细胞白血病（APL）残留疾病标志物的重要作用，并试图阐明其对复发预测的意义。在这项单中心回顾性研究中，我们对117例APL患者在诊断时、诱导化疗后、巩固化疗后以及维持治疗开始后每3个月连续测量PML-RARa和WT1表达。所有117例患者在至少接受2次巩固化疗后均处于分子缓解状态。我们使用WT1 ProfileQuant™试剂盒（Ipsogen）监测WT1。巩固治疗后及维持治疗早期（3个月）WT1高表达（>120拷贝/10 ABL1）显著预测随后的复发。除1例早期复发样本外，所有配对的PML-RARa RQ-PCR均未检测到。维持治疗3个月时WT1高表达的患者（n = 40）复发率显著更高（30.5%对6.9%，P < 0.001），无病生存率更低（62.8%对91.4%，P < 0.001）。多变量分析显示，诊断时白细胞计数高峰高（HR = 6.4，P < 0.001）和维持治疗3个月时WT1高表达（HR = 7.1，P < 0.001）是复发预测的重要因素。我们的数据表明，缓解后WT1高表达是APL后续分子复发预测的可靠标志物。在这个高危组中，全反式维甲酸±三氧化二砷、抗CD33抗体治疗和WT1特异性治疗的早期干预可用于预防复发。
临床研究信息服务（CRIS），KCT0002079。
