{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:29:53Z","timestamp":1790652593659,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood & Cancer"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Diamond\u2010Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long\u2010term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L\u2010leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L\u2010leucine in transfusion\u2010dependent patients with DBA.<\/jats:p>\n <\/jats:sec>\n \n Procedure<\/jats:title>\n \n Patients \u22652 years of age received L\u2010leucine 700 mg\/m\n 2<\/jats:sup>\n orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n This multicenter, phase I\/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5\u201046.1 years). No significant adverse events were attributable to L\u2010leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n L\u2010leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L\u2010leucine in the management of patients with DBA.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pbc.28748","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T03:47:14Z","timestamp":1602042434000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["L\u2010leucine improves anemia and growth in patients with transfusion\u2010dependent Diamond\u2010Blackfan anemia: Results from a multicenter pilot phase I\/II study from the Diamond\u2010Blackfan Anemia Registry"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-5406","authenticated-orcid":false,"given":"Adrianna","family":"Vlachos","sequence":"first","affiliation":[{"name":"Feinstein Institutes for Medical Research Northwell Health Manhasset New York"},{"name":"Division of Hematology\/Oncology and Cellular Therapy, Cohen Children's Medical Center Northwell Health New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Atsidaftos","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research Northwell Health Manhasset New York"},{"name":"Division of Hematology\/Oncology and Cellular Therapy, Cohen Children's Medical Center Northwell Health New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Lutfi","family":"Lababidi","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research Northwell Health Manhasset New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Muir","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research Northwell Health Manhasset New York"},{"name":"Division of Hematology\/Oncology and Cellular Therapy, Cohen Children's Medical Center Northwell Health New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zora R.","family":"Rogers","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center at Dallas Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waseem","family":"Alhushki","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology Cure4 The Kids Foundation Las Vegas Nevada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology Cure 4 The Kids Foundation, Las Vegas, Nevada; presently at Penn State Health Milton S. Hershey Medical Center Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertil","family":"Glader","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Gruner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology University of Missouri Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Hartung","sequence":"additional","affiliation":[{"name":"Division of Hematology The Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Knoll","sequence":"additional","affiliation":[{"name":"The Center for Cancer and Blood Disorders Phoenix Children's Hospital Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Loew","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology University of Missouri, Columbia, Missouri; presently at University of Kansas Medical Center Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-9103","authenticated-orcid":false,"given":"Grzegorz","family":"Nalepa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupama","family":"Narla","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun R.","family":"Panigrahi","sequence":"additional","affiliation":[{"name":"University of Louisville, Louisville, Kentucky; presently at University of California Davis Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A.","family":"Sieff","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Dana\u2010Farber and Boston Children's Cancer and Blood Disorders Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Walkovich","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology C.S. Mott Children's Hospital Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason E.","family":"Farrar","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology Arkansas Children's Research Institute and University of Arkansas for Medical Sciences Little Rock Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research Northwell Health Manhasset New York"},{"name":"Division of Hematology\/Oncology and Cellular Therapy, Cohen Children's Medical Center Northwell Health New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474086.2014.897923"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.10.027"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36633"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63597"},{"key":"e_1_2_10_6_1","first-page":"1241","article-title":"Aplasticanemia (chronicerythroblastophthisis) and cortisone","volume":"81","author":"Gasser C","year":"1951","journal-title":"Schweiz Med Wochenschr"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-251090"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07269.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/5951","article-title":"The gene encoding ribosomal protein S19 is mutated in Diamond\u2010Blackfan anaemia","volume":"21","author":"Gustavsson P","year":"1999","journal-title":"Nat Genet"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-2354-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11498"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-431437"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-382986"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/978-3-319-61421-2_7","volume-title":"Pediatric Oncology, Bone Marrow Failure","author":"Hattangadi S","year":"2018"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.11.010"}],"container-title":["Pediatric Blood & Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.28748","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.28748","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.28748","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T18:54:28Z","timestamp":1693853668000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.28748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,6]]},"references-count":14,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/pbc.28748"],"URL":"https:\/\/doi.org\/10.1002\/pbc.28748","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,6]]},"assertion":[{"value":"2020-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e28748"}}