Sakaguchi Hirotoshi, Nishio Nobuhiro, Hama Asahito, Kawashima Nozomu, Wang Xinan, Narita Atsushi, Doisaki Sayoko, Xu Yinyan, Muramatsu Hideki, Yoshida Nao, Takahashi Yoshiyuki, Kudo Kazuko, Moritake Hiroshi, Nakamura Kazuhiro, Kobayashi Ryoji, Ito Etsuro, Yabe Hiromasa, Ohga Shouichi, Ohara Akira, Kojima Seiji
Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara Division of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya 1 Hospital, Isehara.
Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
Haematologica. 2014 Aug;99(8):1312-6. doi: 10.3324/haematol.2013.091165. Epub 2014 May 9.
Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5-16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41-69%) and 97% (95%CI: 87-99%), respectively. Median telomere length in responders was -0.4 standard deviation (SD) (-2.7 to +3.0 SD) and -1.5 SD (-4.0 to +1.6 (SD)) in non-responders (P<0.001). Multivariate analysis showed that telomere length shorter than -1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19-115; P<0.001), platelet count at diagnosis less than 25×10(9)/L (HR: 13.9; 95%CI: 2.00-96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15-20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia.
预测免疫抑制治疗的反应可为临床医生确定再生障碍性贫血患者的治疗策略提供有用信息。在我们当前的研究中，我们使用流式荧光原位杂交技术评估了64例再生障碍性贫血患儿诊断时淋巴细胞端粒长度与免疫抑制治疗反应之间的关系。患者的中位年龄为10岁（范围1.5 - 16.2岁）。疾病严重程度分为极重度23例、重度21例、中度20例。所有患者均参加了使用抗胸腺细胞球蛋白和环孢素的多中心研究。6个月时免疫抑制治疗的反应率为52%（64例中的33例）。5年无失败生存率和总生存率分别为56%（95%置信区间（CI）：41 - 69%）和97%（95%CI：87 - 99%）。反应者的端粒长度中位数为 - 0.4标准差（SD）（-2.7至 + 3.0 SD），无反应者为 - 1.5 SD（-4.0至 + 1.6 SD）（P<0.001）。多变量分析显示，端粒长度短于 - 1.0 SD（风险比（HR）：22.0；95%CI：4.19 - 115；P<0.001）、诊断时血小板计数低于25×10⁹/L（HR：13.9；95%CI：2.00 - 96.1；P = 0.008）以及从诊断到免疫抑制治疗的间隔时间长于25天（HR：4.81；95%CI：1.15 - 20.1；P = 0.031）是免疫抑制治疗反应不佳的显著变量。与成年患者中发现的情况相反，诊断时测量淋巴细胞端粒长度是预测再生障碍性贫血患儿免疫抑制治疗反应的一种有前景的检测方法。
