title: Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.
abstract: 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.
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Atsushi
authors: A
authors: Narita
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hideki
authors: H
authors: Muramatsu
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yuko
authors: Y
authors: Sekiya
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yusuke
authors: Y
authors: Okuno
authors: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Fujita Health University School of Medicine, Toyoake, Japan.
authors: Hirotoshi
authors: H
authors: Sakaguchi
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Nobuhiro
authors: N
authors: Nishio
authors: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Fujita Health University School of Medicine, Toyoake, Japan.
authors: Nao
authors: N
authors: Yoshida
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Xinan
authors: X
authors: Wang
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yinyan
authors: Y
authors: Xu
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Nozomu
authors: N
authors: Kawashima
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Sayoko
authors: S
authors: Doisaki
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Asahito
authors: A
authors: Hama
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yoshiyuki
authors: Y
authors: Takahashi
authors: Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.
authors: Kazuko
authors: K
authors: Kudo
authors: Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, Hiroshima, Japan.
authors: Hiroshi
authors: H
authors: Moritake
authors: Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Masao
authors: M
authors: Kobayashi
authors: Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Hokkaido, Japan.
authors: Ryoji
authors: R
authors: Kobayashi
authors: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Etsuro
authors: E
authors: Ito
authors: Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan.
authors: Hiromasa
authors: H
authors: Yabe
authors: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Shouichi
authors: S
authors: Ohga
authors: Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
authors: Akira
authors: A
authors: Ohara
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan kojimas@med.nagoya-u.ac.jp.
authors: Seiji
authors: S
authors: Kojima
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D008297:Male; D011379:Prognosis; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis