title: Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group.
abstract: BACKGROUND
  Although the therapeutic outcome of acquired aplastic anemia has improved markedly with the introduction of immunosuppressive therapy using antithymocyte globulin and cyclosporine, a significant proportion of patients subsequently relapse and require second-line therapy. However, detailed analyses of relapses in aplastic anemia children are limited.
  
  
  METHODS
  We previously conducted two prospective multicenter trials of immunosuppressive therapy for children with aplastic anemia: AA-92 and AA-97, which began in 1992 and 1997, respectively. In this study, we assessed the relapse rate, risk factors for relapse, and the response to second-line treatment in children with aplastic anemia treated with antithymocyte globulin and cyclosporine.
  
  
  RESULTS
  From 1992 to 2007, we treated 441 children with aplastic anemia with standard immunosuppressive therapy. Among the 264 patients who responded to immunosuppressive therapy, 42 (15.9%) relapsed. The cumulative incidence of relapse was 11.9% at 10 years. Multivariate analysis revealed that relapse risk was significantly associated with an immunosuppressive therapy regimen using danazol (relative risk, 3.15; P=0.001) and non-severe aplastic anemia (relative risk, 2.51; P=0.02). Seventeen relapsed patients received additional immunosuppressive therapy with antithymocyte globulin and cyclosporine. Eight patients responded within 6 months. Seven of nine non-responders to second immunosuppressive therapy received hematopoietic stem cell transplantation and five are alive. Eleven patients underwent hematopoietic stem cell transplantation directly and seven are alive.
  
  
  CONCLUSIONS
  In the present study, the cumulative incidence of relapse at 10 years was relatively low compared to that in other studies mainly involving adult patients. A multicenter prospective study is warranted to establish optimal therapy for children with aplastic anemia.
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kamio
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Ohara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagasaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Mugishima
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kikuta
authors.forename: Yuko
authors.initials: Y
authors.lastname: Osugi
authors.forename: Fumio
authors.initials: F
authors.lastname: Bessho
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsukimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000453:epidemiology / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine