{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:07:20Z","timestamp":1772165240146,"version":"3.50.1"},"reference-count":31,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL+), we compared the outcome of MLL+ patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL+. Among the 277 of 297 MLL+ patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g\/L. Ninety-seven of 297 MLL+ patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL+ acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487.<\/jats:p>","DOI":"10.1182\/blood-2010-03-273532","type":"journal-article","created":{"date-parts":[[2010,6,30]],"date-time":"2010-06-30T22:55:12Z","timestamp":1277938512000},"page":"2644-2650","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":148,"title":["Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)\u2013rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study"],"prefix":"10.1182","volume":"116","author":[{"given":"Georg","family":"Mann","sequence":"first","affiliation":[{"name":"Berlin-Frankfurt-M\u00fcnster Study Group, Austria;"}]},{"given":"Andishe","family":"Attarbaschi","sequence":"additional","affiliation":[{"name":"Berlin-Frankfurt-M\u00fcnster Study Group, Austria;"}]},{"given":"Martin","family":"Schrappe","sequence":"additional","affiliation":[{"name":"Berlin-Frankfurt-M\u00fcnster Study Group, Germany;"}]},{"given":"Paola","family":"De Lorenzo","sequence":"additional","affiliation":[{"name":"Interfant-99 Trial Data Center, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy;"}]},{"given":"Christina","family":"Peters","sequence":"additional","affiliation":[{"name":"Berlin-Frankfurt-M\u00fcnster Study Group, Austria;"}]},{"given":"Ian","family":"Hann","sequence":"additional","affiliation":[{"name":"United Kingdom Children's Cancer Study Group, United Kingdom;"}]},{"given":"Giulio","family":"De Rossi","sequence":"additional","affiliation":[{"name":"Associazione Italiana Ematologia Oncologia Pediatrica, Italy;"}]},{"given":"Maria","family":"Felice","sequence":"additional","affiliation":[{"name":"Argentinean Group of Pediatric Hematology and Oncology, Buenos Aires, Argentina;"}]},{"given":"Birgitte","family":"Lausen","sequence":"additional","affiliation":[{"name":"Nordic Society of Pediatric Hematology and Oncology, Norway, Sweden, Denmark, Finland, and Iceland;"}]},{"given":"Thierry","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"French Acute Lymphoblastic Leukemia Study Group, France;"}]},{"given":"Tomasz","family":"Szczepanski","sequence":"additional","affiliation":[{"name":"Polish Pediatric Leukemia and Lymphoma Study Group, Poland;"}]},{"given":"Alina","family":"Ferster","sequence":"additional","affiliation":[{"name":"Children's Leukemia Group, France, Belgium, and Portugal;"}]},{"given":"Gritta","family":"Janka-Schaub","sequence":"additional","affiliation":[{"name":"Cooperative Acute Lymphoblastic Leukemia Study Group, Germany;"}]},{"given":"Jeffrey","family":"Rubnitz","sequence":"additional","affiliation":[{"name":"St Jude Children's Research Hospital, Memphis, TN;"}]},{"given":"Lewis B.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute ALL Consortium, Boston, MA;"}]},{"given":"Jan","family":"Stary","sequence":"additional","affiliation":[{"name":"Czech Pediatric Haematology, Czech Republic;"}]},{"given":"Myriam","family":"Campbell","sequence":"additional","affiliation":[{"name":"Programa Infantil Nacional de Drogas Antineopl\u00e1sicas, Chile;"}]},{"given":"Chi Kong","family":"Li","sequence":"additional","affiliation":[{"name":"Hong Kong Pediatric Hematology and Oncology Study Group, Hong Kong, China;"}]},{"given":"Ram","family":"Suppiah","sequence":"additional","affiliation":[{"name":"Australian and New Zealand Children's Haematology and Oncology Study Group, Australia; and"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"Associazione Italiana Ematologia Oncologia Pediatrica, Italy;"}]},{"given":"Ajay","family":"Vora","sequence":"additional","affiliation":[{"name":"United Kingdom Children's Cancer Study Group, United Kingdom;"}]},{"given":"Maria Grazia","family":"Valsecchi","sequence":"additional","affiliation":[{"name":"Interfant-99 Trial Data Center, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy;"}]},{"given":"Rob","family":"Pieters","sequence":"additional","affiliation":[{"name":"Dutch Childhood Oncology Study Group, Erasmus MC-Sophia Children's Hospital, The Netherlands"}]},{"name":"on behalf of the Interfant-99 Study Group","sequence":"additional","affiliation":[]}],"member":"234","reference":[{"issue":"1","key":"2019111723465551800_B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1182\/blood.V96.1.24","article-title":"Biological and therapeutic aspects of infant leukemia.","volume":"96","author":"Biondi","year":"2000","journal-title":"Blood"},{"issue":"9","key":"2019111723465551800_B2","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/sj.leu.2402595","article-title":"Infant acute lymphoblastic leukemia: combined cytogenetic, immunophenotypical and molecular analysis of 77 cases.","volume":"16","author":"Borkhardt","year":"2002","journal-title":"Leukemia"},{"issue":"4","key":"2019111723465551800_B3","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/sj.leu.2404577","article-title":"Acute lymphoblastic leukemia with t(4;11) in children 1 year and older: the \u2018big sister\u2019 of the infant disease?","volume":"21","author":"Mann","year":"2007","journal-title":"Leukemia"},{"issue":"4","key":"2019111723465551800_B4","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1182\/blood.V94.4.1209","article-title":"Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia.","volume":"94","author":"D\u00f6rdelmann","year":"1999","journal-title":"Blood"},{"key":"2019111723465551800_B5","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1002\/pbc.21352","article-title":"Acute lymphoblastic leukemia in infancy.","volume":"49","author":"Silverman","year":"2007","journal-title":"Pediatr Blood Cancer"},{"issue":"9583","key":"2019111723465551800_B6","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0140-6736(07)61126-X","article-title":"A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomized trial.","volume":"370","author":"Pieters","year":"2007","journal-title":"Lancet"},{"issue":"5","key":"2019111723465551800_B7","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/sj.leu.2404150","article-title":"The MLL recombinome of acute leukemias.","volume":"20","author":"Meyer","year":"2006","journal-title":"Leukemia"},{"key":"2019111723465551800_B8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bbmt.2008.10.015","article-title":"Controversies of and unique issues in hematopoietic cell transplantation for infant leukemia.","volume":"15","author":"Hunger","year":"2009","journal-title":"Biol Blood Marrow Transplant"},{"issue":"7","key":"2019111723465551800_B9","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/sj.leu.2401818","article-title":"Late effects in survivors of infant leukemia.","volume":"14","author":"Leung","year":"2000","journal-title":"Leukemia"},{"issue":"11","key":"2019111723465551800_B10","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1038\/sj.leu.2404903","article-title":"Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group.","volume":"21","author":"Tomizawa","year":"2007","journal-title":"Leukemia"},{"issue":"4","key":"2019111723465551800_B11","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/sj.leu.2402883","article-title":"Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.","volume":"17","author":"Pui","year":"2003","journal-title":"Leukemia"},{"issue":"9321","key":"2019111723465551800_B12","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/S0140-6736(02)08782-2","article-title":"Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region.","volume":"359","author":"Pui","year":"2002","journal-title":"Lancet"},{"issue":"6","key":"2019111723465551800_B13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/mpo.2950200603","article-title":"Minimal requirements for the diagnosis, classification, and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the \u201dBFM Family\u201d Cooperative Group.","volume":"20","author":"van der Does-van den Berg","year":"1992","journal-title":"Med Pediatr Oncol"},{"issue":"10","key":"2019111723465551800_B14","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1158\/1078-0432.CCR-05-2861","article-title":"Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity.","volume":"12","author":"Attarbaschi","year":"2006","journal-title":"Clin Cancer Res"},{"issue":"8","key":"2019111723465551800_B15","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.ejca.2009.01.011","article-title":"Evaluation of alternative prognostic stratifications by prediction accuracy measures on individual survival with application to childhood leukaemia.","volume":"45","author":"De Lorenzo","year":"2009","journal-title":"Eur J Cancer"},{"issue":"9486","key":"2019111723465551800_B16","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0140-6736(05)66998-X","article-title":"Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomization in an international prospective study.","volume":"366","author":"Balduzzi","year":"2005","journal-title":"Lancet"},{"issue":"36","key":"2019111723465551800_B17","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1200\/JCO.2006.06.2679","article-title":"Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95.","volume":"24","author":"Schrauder","year":"2006","journal-title":"J Clin Oncol"},{"issue":"12","key":"2019111723465551800_B18","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.bbmt.2005.08.031","article-title":"Favorable outcome for infant acute lymphoblastic leukemia after hematopoietic stem cell transplantation.","volume":"11","author":"Jacobsohn","year":"2005","journal-title":"Biol Blood Marrow Transplant"},{"issue":"9","key":"2019111723465551800_B19","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.1182\/blood-2004-08-3312","article-title":"Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia.","volume":"105","author":"Sanders","year":"2005","journal-title":"Blood"},{"issue":"18","key":"2019111723465551800_B20","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1200\/JCO.2000.18.18.3256","article-title":"High survival rate in infant acute leukemia treated with early high-dose chemotherapy and stem-cell support: Groupo Espanol de Trasplante de Medula Osea en Ninos.","volume":"18","author":"Marco","year":"2000","journal-title":"J Clin Oncol"},{"issue":"12","key":"2019111723465551800_B21","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1182\/blood-2004-04-1390","article-title":"Infant acute lymphoblastic leukemia with MLL gene rearrangements: outcome following intensive chemotherapy and hematopoietic stem cell transplantation.","volume":"104","author":"Kosaka","year":"2004","journal-title":"Blood"},{"issue":"1","key":"2019111723465551800_B22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1200\/JCO.2005.02.4612","article-title":"Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months.","volume":"24","author":"Eapen","year":"2006","journal-title":"J Clin Oncol"},{"key":"2019111723465551800_B23","doi-asserted-by":"crossref","first-page":"9514","DOI":"10.1200\/jco.2007.25.18_suppl.9514","article-title":"Hematopoietic stem cell transplant (HSCT) versus intensive chemotherapy in infant acute lymphoblastic leukemia [abstract].","volume":"25","author":"Dreyer","year":"2007","journal-title":"J Clin Oncol"},{"issue":"2","key":"2019111723465551800_B24","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1046\/j.1365-2141.2002.03442.x","article-title":"Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987-1999.","volume":"117","author":"Chessells","year":"2002","journal-title":"Br J Haematol"},{"issue":"7","key":"2019111723465551800_B25","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/pbc.21207","article-title":"Long-term follow-up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age.","volume":"49","author":"Perkins","year":"2007","journal-title":"Pediatr Blood Cancer"},{"issue":"6","key":"2019111723465551800_B26","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/leu.2009.17","article-title":"Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol.","volume":"23","author":"Van der Velden","year":"2009","journal-title":"Leukemia"},{"issue":"4","key":"2019111723465551800_B27","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/sj.leu.2404535","article-title":"Optimization of PCR-based minimal residual disease diagnostics for childhood acute lymphoblastic leukemia in a multi-center setting.","volume":"21","author":"van der Velden","year":"2007","journal-title":"Leukemia"},{"issue":"7","key":"2019111723465551800_B28","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1182\/blood-2004-09-3667","article-title":"Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia.","volume":"106","author":"Stam","year":"2005","journal-title":"Blood"},{"issue":"7","key":"2019111723465551800_B29","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/leu.2009.72","article-title":"Immunoglobulin and T-cell receptor gene rearrangements as PCR-based targets are stable markers for monitoring minimal residual disease in acute lymphoblastic leukemia after stem cell transplantation.","volume":"23","author":"Kreyenberg","year":"2009","journal-title":"Leukemia"},{"key":"2019111723465551800_B30","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bbmt.2008.11.009","article-title":"Allogeneic transplantation for pediatric acute lymphoblastic leukemia: the emerging role of peritransplantation minimal residual disease\/chimerism monitoring and novel chemotherapeutic, molecular, and immune approaches aimed at preventing relapse.","volume":"15","author":"Pulsipher","year":"2009","journal-title":"Biol Blood Marrow Transplant"},{"issue":"27","key":"2019111723465551800_B31","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.1182\/blood-2009-06-227660","article-title":"Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options.","volume":"114","author":"Stumpel","year":"2009","journal-title":"Blood"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/116\/15\/2644\/1329742\/zh804110002644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/116\/15\/2644\/1329742\/zh804110002644.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,6]],"date-time":"2020-06-06T05:22:52Z","timestamp":1591420972000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/116\/15\/2644\/27654\/Improved-outcome-with-hematopoietic-stem-cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,14]]},"references-count":31,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2010,10,14]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2010-03-273532","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.6928956.7119054","asserted-by":"object"}]},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,14]]}}}