title: Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishio
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kawashima
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Xinan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Narita
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Doisaki
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.affiliation: Division of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya 1 Hospital, Isehara.
authors.forename: Nao
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Division of Hematology and Oncology, Shizuoka Children's Hospital, Isehara.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, Isehara.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moritake
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Isehara.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Isehara.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Isehara.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.affiliation: Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.affiliation: Department of Perinatal and Pediatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.affiliation: Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ohara
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Isehara kojimas@med.nagoya-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D016615:Telomere / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D059505:Telomere Homeostasis / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents