title: First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.
abstract: The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992-1999 versus 2000-2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya;
authors.forename: Nao
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Isehara;
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
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 Pediatrics, Hyogo Children's Hospital, Kobe;
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Department of Pediatrics, Nihon University School of Medicine, Tokyo;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagasaki
authors.affiliation: Division of Hematology and Oncology, Shizuoka Children's Hospital, Toyoake;
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Fujita Health University School of Medicine, Toyoake;
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke;
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.affiliation: Department of Perinatal and Pediatric Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka;
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Tokyo, Japan;
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Tokyo, Japan;
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya;
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of HSCT Data Management & Biostatistics, Nagoya University Graduate School of Medicine, Tokyo, Japan;
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
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, Tokyo, Japan; kojimas@med.nagoya-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine