Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia

Hirotoshi Sakaguchi, Nobuhiro Nishio, Asahito Hama, Nozomu Kawashima, Xinan Wang, Atsushi Narita, Sayoko Doisaki, Yinyan Xu, Hideki Muramatsu, Nao Yoshida, Yoshiyuki Takahashi, Kazuko Kudo, Hiroshi Moritake, Kazuhiro Nakamura, Ryoji Kobayashi, Etsuro Ito, Hiromasa Yabe, Shouichi Ohga, Akira Ohara, Seiji Kojima

Research output: Contribution to journalArticle

23 Citations (Scopus)


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 25×109/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.

Original languageEnglish
Pages (from-to)1312-1316
Number of pages5
Issue number8
Publication statusPublished - Aug 1 2014


All Science Journal Classification (ASJC) codes

  • Hematology

Cite this