title: Treatment-related adverse events associated with a modified UK ALLR3 induction chemotherapy backbone for childhood relapsed/refractory acute lymphoblastic leukemia.
abstract: 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.
  
  
  
  We performed a multi-institutional, 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.
  
  
  
  Fifty-nine patients were included in the study, including 16 patients with ≥2nd relapse. Ninety-seven percent of patients experienced at least one Grade ≥3 nonhematologic adverse event (AE). Grade 3 or higher infection was reported in 90% of patients. Other nonhematologic Grade ≥3 AEs included electrolyte abnormalities, elevation in hepatic enzymes, and pain. Eighty-five 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 ≥2nd relapse.
  
  
  
  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.
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, California. wsun@chla.usc.edu.|Keck School of Medicine, USC-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California. wsun@chla.usc.edu.
authors.forename: Weili
authors.initials: W
authors.lastname: Sun
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, California.|Keck School of Medicine, USC-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Etan
authors.initials: E
authors.lastname: Orgel
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, California.
authors.forename: Jemily
authors.initials: J
authors.lastname: Malvar
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, California.|Keck School of Medicine, USC-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.affiliation: Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wilkes
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gardner
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Vanessa P
authors.initials: VP
authors.lastname: Tolbert
authors.affiliation: Keck School of Medicine, USC-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Alison
authors.initials: A
authors.lastname: Smith
authors.affiliation: School of Medicine, St. Louis University, St. Louis, Missouri.
authors.forename: Minjun
authors.initials: M
authors.lastname: Hur
authors.affiliation: Keck School of Medicine, USC-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.|Infectious Disease, Children's Hospital Los Angeles, California.
authors.forename: Jill
authors.initials: J
authors.lastname: Hoffman
authors.affiliation: Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rheingold
authors.affiliation: Pediatric Leukemia and Lymphoma, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Burke
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, California.|Keck School of Medicine, USC-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies
keywords: adverse events; reinduction; relapsed ALL