Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
J Clin Oncol. 2012 Mar 1;30(7):735-41. doi: 10.1200/JCO.2011.36.9868. Epub 2012 Jan 30.
Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain.
We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning.
Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 × 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; ± standard deviation) was higher (30% ± 5% v 16% ± 5%; P = .006) and leukemia-free survival (LFS) lower (58% ± 5% v 71% ± 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR.
FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.
如果仅接受化疗治疗，患有急性髓系白血病（AML）和 FLT3 内部串联重复（FLT3/ITD）的患者预后较差。该改变是否会影响异基因造血干细胞移植（HSCT）后的结果尚不确定。
我们分析了 206 例接受 HLA 匹配的同胞和匹配的无关供体 HSCT 的患者，这些患者被欧洲血液和骨髓移植组报告为具有正常细胞遗传学和 FLT3/ITD 数据的 AML 诊断[存在：n = 120（58%）；不存在：n = 86（42%）]。移植在接受清髓性调理后达到完全缓解（CR）时进行。
与 FLT3/ITD 阴性患者相比，FLT3/ITD 阳性患者的诊断时白细胞计数中位数较高（59×109/L 与 21×109/L；P <.001），从 CR 到移植的时间间隔较短（87 天与 99 天；P =.04）。两组的其他特征相似。2 年时，FLT3/ITD 阳性患者的复发率（RI；±标准差）较高（30%±5%与 16%±5%；P =.006），无白血病生存率（LFS）较低（58%±5%与 71%±6%；P =.04）。在多变量分析中，FLT3/ITD 导致 RI 增加（危险比 [HR]，3.4；95%置信区间，1.46 至 7.94；P =.005），年龄较大、女性、CR 与移植之间的时间间隔较短、CR 前接受的化疗疗程数较多也是 RI 增加的原因。FLT3/ITD 阳性与 LFS 降低相关（HR，0.37；95%置信区间，0.19 至 0.73；P =.002），同时与年龄较大和 CR 前接受的化疗疗程数较多有关。
FLT3/ITD 对 HSCT 的结果产生了与化疗相同的不利影响；尽管如此，接受移植的携带这种突变的患者中仍有一半以上在 2 年时仍存活且无白血病。为了进一步提高结果，在 HSCT 前后使用 FLT3 抑制剂值得研究。
