Divisione Ematologia e Trapianto di Midollo, IRCCS San Martino-IST, Genova, Italy.
Br J Haematol. 2013 Feb;160(4):503-9. doi: 10.1111/bjh.12181. Epub 2013 Jan 7.
We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.
我们评估了 122 例急性髓系白血病(AML)患者骨髓细胞中的 WT1 表达(表示为信使拷贝/10(4) ABL1),这些患者在未进行干预的异基因造血干细胞移植(HSCT)前后。中位年龄为 44 岁(15-69 岁),59%处于首次缓解期,74%接受了清髓性预处理方案,中位随访时间为 865 天(34-2833 天)。在 HSCT 后任何时间,WT1 表达的 67 例患者的复发率更高,超过 100 拷贝(54%),而 WT1 表达<100 拷贝的 55 例患者为 16%(P<0·0001)。同样,5 年总生存率(OS)分别为 40%和 63%(P=0·03)。多变量 Cox 分析显示,HSCT 后 WT1 表达是复发的最强预测因素(危险比[HR] 4·5,P=0·0001),独立于疾病阶段(HR 2·3,P=0·002)。由于 WT1 水平升高,17 例患者接受了供者淋巴细胞输注(DLI):他们的 OS 为 44%,而 21 例未接受 DLI 且 WT1 表达增加的患者的 OS 为 14%(P=0·004)。总之,HSCT 后 WT1 表达是 AML 白血病复发和生存的强有力预测因子;WT1 可作为早期干预治疗的标志物。