Wong Eric, Mason Kate, Collins Jenny, Hockridge Barbara, Boyd Janis, Gorelik Alexandra, Szer Jeffrey, Ritchie David S
Bone Marrow Transplant Service, Royal Melbourne Hospital, Victoria, Australia; Bone Marrow Transplant Service, University of Melbourne, Victoria, Australia.
Bone Marrow Transplant Service, Royal Melbourne Hospital, Victoria, Australia.
Biol Blood Marrow Transplant. 2017 May;23(5):840-844. doi: 10.1016/j.bbmt.2017.01.086. Epub 2017 Feb 6.
Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease.
供体T细胞嵌合现象与急性髓系白血病（AML）和骨髓增生异常综合征（MDS）异基因干细胞移植（alloSCT）后的复发结局相关。然而，统计关联度的衡量方法并不能充分评估一种预后生物标志物的性能，而预后生物标志物的最佳特征是其对所选结局的敏感性和特异性。我们分析了103例接受清髓性alloSCT治疗AML或MDS的患者在第100天（D100chim）时的供体T细胞嵌合结果，并确定了其对alloSCT后6个月（RFS6）和12个月（RFS12）无复发生存的敏感性和特异性。RFS6的受试者工作特征曲线下面积为0.68，表明其作为预测生物标志物的效用一般，尽管这一数值高于RFS12的0.62。使用65%的D100chim阈值，RFS6的特异性为96.6%；然而，敏感性较差，为26.7%。这相当于阴性预测值为88.5%，阳性预测值为57.1%。将D100chim的阈值改为75%或85%，可适度提高D100chim对RFS6的敏感性；然而，这是以牺牲特异性为代价的。D100chim具有特异性，但作为AML或MDS清髓性alloSCT后早期RFS的预后生物标志物缺乏敏感性。在使用D100chim指导包括免疫调节在内的治疗决策时需谨慎，因为这可能会使患者遭受不必要的移植物抗宿主病。
