{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:03:39Z","timestamp":1789016619342,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T00:00:00Z","timestamp":1468972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The UK ALLR3 (R3) regimen has been adopted to treat pediatric relapsed acute lymphoblastic leukemia (ALL) by many centers in the United States and has become a preferred therapeutic backbone for testing novel agents in clinical trials. A detailed toxicity profile of this platform has not previously been reported. The toxicity and response rates for its use beyond first relapse are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>We performed a multi\u2010institutional, retrospective study including children with relapsed ALL treated with the R3 reinduction chemotherapy backbone block 1 across five pediatric centers. Data were extracted from medical records and analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010nine patients were included in the study, including 16 patients with \u22652nd relapse. Ninety\u2010seven percent of patients experienced at least one Grade \u22653 nonhematologic adverse event (AE). Grade 3 or higher infection was reported in 90% of patients. Other nonhematologic Grade \u22653 AEs included electrolyte abnormalities, elevation in hepatic enzymes, and pain. Eighty\u2010five percent of patients achieved a complete remission (CR). There were no significant differences in the incidence of AEs, CR rate, and rate of minimal residual disease negativity between patients with 1st or \u22652nd relapse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study confirmed that R3 block 1 is a highly active reinduction regimen in childhood relapsed ALL. However, it was associated with a high incidence of severe toxicities, particularly infection. The toxicity profiled in our report should be used to inform optimal supportive care and future clinical trial design with the R3 backbone, particularly when new agents are combined with this regimen.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26129","type":"journal-article","created":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T14:48:41Z","timestamp":1469026121000},"page":"1943-1948","source":"Crossref","is-referenced-by-count":27,"title":["Treatment\u2010related adverse events associated with a modified UK ALLR3 induction chemotherapy backbone for childhood relapsed\/refractory acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"63","author":[{"given":"Weili","family":"Sun","sequence":"first","affiliation":[{"name":"Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  California"},{"name":"Keck School of Medicine USC\u2010Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etan","family":"Orgel","sequence":"additional","affiliation":[{"name":"Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  California"},{"name":"Keck School of Medicine USC\u2010Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemily","family":"Malvar","sequence":"additional","affiliation":[{"name":"Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sposto","sequence":"additional","affiliation":[{"name":"Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  California"},{"name":"Keck School of Medicine USC\u2010Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Wilkes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Oncology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seattle Children's Hospital  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa P.","family":"Tolbert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seattle Children's Hospital  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Smith","sequence":"additional","affiliation":[{"name":"Keck School of Medicine USC\u2010Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjun","family":"Hur","sequence":"additional","affiliation":[{"name":"School of Medicine St. Louis University  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Keck School of Medicine USC\u2010Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"},{"name":"Infectious Disease Children's Hospital Los Angeles  California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Rheingold","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Oncology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Burke","sequence":"additional","affiliation":[{"name":"Pediatric Leukemia and Lymphoma Children's Hospital of Wisconsin Medical College of Wisconsin  Milwaukee Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Wayne","sequence":"additional","affiliation":[{"name":"Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  California"},{"name":"Keck School of Medicine USC\u2010Norris Comprehensive Cancer Center University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.261"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.8018"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.251"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.2950"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.1414"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-294678"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.1031"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.1983"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62002-8"},{"key":"e_1_2_7_11_1","unstructured":"ClinicalTRials.gov. A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01483690?term=NCT+01483690&rank=1. Accessed January 6 2016."},{"key":"e_1_2_7_12_1","unstructured":"ClinicalTRials.gov. Study of Carfilzomib in Combination With Dexamethasone Mitoxantrone PEG\u2010asparaginase and Vincristine in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02303821?term=NCT02303821&rank=1. Accessed January 6 2016."},{"key":"e_1_2_7_13_1","unstructured":"ClinicalTRials.gov. Temsirolimus Dexamethasone Mitoxantrone Hydrochloride Vincristine Sulfate and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non\u2010Hodgkin Lymphoma.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01403415?term=NCT01403415&rank=1. Accessed January 6 2016."},{"key":"e_1_2_7_14_1","unstructured":"ClinicalTRials.gov. 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