Nishiwaki S, Imai K, Mizuta S, Kanamori H, Ohashi K, Fukuda T, Onishi Y, Takahashi S, Uchida N, Eto T, Nakamae H, Yujiri T, Mori S, Nagamura-Inoue T, Suzuki R, Atsuta Y, Tanaka J
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, Japan.
Bone Marrow Transplant. 2016 Jan;51(1):43-50. doi: 10.1038/bmt.2015.217. Epub 2015 Sep 21.
To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(-)) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD(-) was significantly better than that in patients transplanted in MRD(+) (MRD(-): 67% vs MRD(+): 55% at 4 years; P=0.001). MRD(-) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD(-) was significantly lower than that in patients transplanted in MRD(+) (MRD(-): 19% vs MRD(+): 29% at 4 years; P=0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P<0.0001). MRD status at allo-HCT is one of the most important predictive factors for Ph+ALL patients transplanted in CR1.
为评估微小残留病(MRD)和酪氨酸激酶抑制剂(TKI)给药对Ph阳性急性淋巴细胞白血病(Ph+ALL)患者异基因造血细胞移植(allo-HCT)的影响,我们回顾性分析了登记数据库中432例接受移植前TKI给药的首次完全缓解(CR1)成年Ph+ALL患者的数据。277例患者在allo-HCT时达到MRD阴性(MRD(-))。MRD(-)患者的总生存期(OS)显著优于MRD(+)患者(4年时MRD(-):67% vs MRD(+):55%;P=0.001)。在多因素分析中,allo-HCT时的MRD(-)以及allo-HCT时的年龄是生存的显著危险因素。MRD(-)患者的复发率显著低于MRD(+)患者(4年时MRD(-):19% vs MRD(+):29%;P=0.006)。在多因素分析中,allo-HCT时的MRD(+)是复发的显著危险因素。103例患者接受了移植后TKI治疗。在关于移植后TKI给药效果的亚组分析中,移植后TKI给药在多因素分析中是复发的显著危险因素(P<0.0001)。allo-HCT时的MRD状态是CR1期接受移植的Ph+ALL患者最重要的预测因素之一。