Narita Atsushi, Muramatsu Hideki, Sekiya Yuko, Okuno Yusuke, Sakaguchi Hirotoshi, Nishio Nobuhiro, Yoshida Nao, Wang Xinan, Xu Yinyan, Kawashima Nozomu, Doisaki Sayoko, Hama Asahito, Takahashi Yoshiyuki, Kudo Kazuko, Moritake Hiroshi, Kobayashi Masao, Kobayashi Ryoji, Ito Etsuro, Yabe Hiromasa, Ohga Shouichi, Ohara Akira, Kojima Seiji
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Fujita Health University School of Medicine, Toyoake, Japan.
Haematologica. 2015 Dec;100(12):1546-52. doi: 10.3324/haematol.2015.132530. Epub 2015 Aug 27.
Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972.
获得性再生障碍性贫血是一种免疫介导的疾病，其特征是干细胞数量严重缺陷，导致骨髓细胞减少和外周血细胞减少。微小阵发性睡眠性血红蛋白尿群体和短端粒长度被确定为再生障碍性贫血免疫抑制治疗反应性的预测生物标志物。我们招募了113例再生障碍性贫血患者（63名男孩和50名女孩）参与本研究，以评估他们对免疫抑制治疗的反应。通过流式细胞术检测阵发性睡眠性血红蛋白尿群体和端粒长度。47例患者（42%）携带微小阵发性睡眠性血红蛋白尿群体。再生障碍性贫血患者的端粒长度中位数为-0.99标准差（SD）（范围为-4.01至+3.01 SD）。总体而言，60例患者（53%）在6个月后对免疫抑制治疗有反应。多因素逻辑回归分析确定，不存在阵发性睡眠性血红蛋白尿群体和较短的端粒长度是6个月时免疫抑制治疗反应的独立不利预测因素。该队列分别分为预后不良组（阵发性睡眠性血红蛋白尿阴性且端粒长度较短；37例患者）和预后良好组（阵发性睡眠性血红蛋白尿阳性和/或端粒长度较长；76例患者）。预后不良组和预后良好组在6个月时的反应率分别为19%和70%（P<0.001）。微小阵发性睡眠性血红蛋白尿群体缺失和端粒长度短的联合情况是免疫抑制治疗反应不良的有效预测指标，在决定治疗方案（免疫抑制治疗或一线造血干细胞移植）时应予以考虑。该试验已在www.umin.ac.jp注册，注册号为UMIN000017972。
