{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:36:53Z","timestamp":1788356213803,"version":"build-2803163510"},"reference-count":21,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS\/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7\u2009\u00b1\u20093.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7\/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.<\/jats:p>","DOI":"10.1182\/blood.v100.3.786","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T18:33:52Z","timestamp":1034361232000},"page":"786-790","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":152,"title":["Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children"],"prefix":"10.1182","volume":"100","author":[{"given":"Seiji","family":"Kojima","sequence":"first","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ohara","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Tsuchida","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kudoh","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Hanada","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Okimoto","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikuni","family":"Takano","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Ikuta","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Tsukimoto","sequence":"additional","affiliation":[{"name":"From the multicenter collaborative study group, Japan Childhood Aplastic Anemia Study Group."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021222050214100_B1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0037-1963(00)90033-7","article-title":"Late clonal diseases of treated aplastic anemia.","volume":"37","author":"Socie","year":"2000","journal-title":"Semin Hematol."},{"key":"2020021222050214100_B2","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1056\/NEJM199205073261917","article-title":"Myelodysplasia and leukemia after treatment of aplastic anemia with G-CSF.","volume":"326","author":"Kojima","year":"1992","journal-title":"N Engl J Med."},{"key":"2020021222050214100_B3","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1182\/blood.V90.3.1009","article-title":"Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.","volume":"90","author":"Ohara","year":"1997","journal-title":"Blood."},{"key":"2020021222050214100_B4","first-page":"429","article-title":"Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy.","volume":"96","author":"Freedman","year":"2000","journal-title":"Blood."},{"key":"2020021222050214100_B5","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1182\/blood.V67.5.1448.1448","article-title":"Effects of clonogenic cells in acute myeloblastic leukemia.","volume":"67","author":"Griffin","year":"1986","journal-title":"Blood."},{"key":"2020021222050214100_B6","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1182\/blood.V96.6.2049","article-title":"Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia.","volume":"96","author":"Kojima","year":"2000","journal-title":"Blood."},{"key":"2020021222050214100_B7","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1182\/blood.V48.1.63.63","article-title":"Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality.","volume":"48","author":"Camitta","year":"1976","journal-title":"Blood."},{"key":"2020021222050214100_B8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1365-2141.1982.tb08475.x","article-title":"Proposals for the classification of the myelodysplastic syndromes.","volume":"51","author":"Bennett","year":"1982","journal-title":"Br J Haematol."},{"key":"2020021222050214100_B9","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/01621459.1958.10501452","article-title":"Nonparametric estimation from incomplete observations.","volume":"53","author":"Kaplan","year":"1958","journal-title":"J Am Stat Assoc."},{"key":"2020021222050214100_B10","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1055\/s-2008-1043875","article-title":"Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience.","volume":"210","author":"Fuhrer","year":"1998","journal-title":"Klin Padiatr."},{"key":"2020021222050214100_B11","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1182\/blood.V95.6.1931","article-title":"Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO\/EBMT study on 100 patients.","volume":"95","author":"Bacigalupo","year":"2000","journal-title":"Blood."},{"key":"2020021222050214100_B12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0140-6736(00)03574-1","article-title":"Treatment of aplastic anemia with granulocyte-colony stimulating factor and risk of malignancy.","volume":"357","author":"Locasciulli","year":"2001","journal-title":"Lancet."},{"key":"2020021222050214100_B13","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1056\/NEJM199310143291603","article-title":"Malignant tumors occurring after treatment of aplastic anemia.","volume":"29","author":"Socie","year":"1993","journal-title":"New Engl J Med."},{"key":"2020021222050214100_B14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1046\/j.1365-2141.1998.01014.x","article-title":"Long-term administration of G-CSF for aplastic anaemia is closely related to the early evolution of monosomy 7 MDS in adults.","volume":"103","author":"Kaito","year":"1998","journal-title":"Br J Haematol."},{"key":"2020021222050214100_B15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1365-2141.1988.tb02382.x","article-title":"Late haematological complications in severe aplastic anaemia.","volume":"69","author":"Tichelli","year":"1988","journal-title":"Br J Haematol."},{"key":"2020021222050214100_B16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1046\/j.1365-2141.1999.01187.x","article-title":"Abnormal cytogenetic clones in patients with aplastic anaemia: response to immunosuppressive therapy.","volume":"104","author":"Geary","year":"1999","journal-title":"Br J Haematol."},{"key":"2020021222050214100_B17","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1046\/j.1365-2141.1999.01729.x","article-title":"Coexistence of normal and clonal haematopoiesis in aplastic anaemia patients treated with immunosuppressive therapy.","volume":"107","author":"Piaggio","year":"1999","journal-title":"Br J Haematol."},{"key":"2020021222050214100_B18","first-page":"13","article-title":"Instability of chromosome 7 in colony forming cells of patients with aplastic anemia.","volume":"70","author":"Ueda","year":"1999","journal-title":"Int J Hematol."},{"key":"2020021222050214100_B19","first-page":"354a","article-title":"Appearance of monosomy 7 in cultures of bone marrow cells from patients with myelodysplasia after exposure in vitro to granulocyte-colony stimulating factor [abstract].","volume":"96","author":"Kim","year":"2000","journal-title":"Blood."},{"key":"2020021222050214100_B20","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1182\/blood.V77.10.2225.2225","article-title":"Correlation of response of aplastic anemia to antilymphocyte globulin with in vitro lymphocyte stimulatory effect: predictive value of in vitro test for clinical response.","volume":"77","author":"Abe","year":"1991","journal-title":"Blood."},{"key":"2020021222050214100_B21","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1056\/NEJM199009273231317","article-title":"Cyclosporine and recombinant granulocyte colony-stimulating factor in severe aplastic anemia.","volume":"323","author":"Kojima","year":"1990","journal-title":"New Engl J Med."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/100\/3\/786\/1684761\/h81502000786.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/100\/3\/786\/1684761\/h81502000786.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T03:10:34Z","timestamp":1581563434000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/100\/3\/786\/16393\/Risk-factors-for-evolution-of-acquired-aplastic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,8,1]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,8,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v100.3.786","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2002,8,1]]}}}