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Treatment-related adverse events associated with a modified UK ALLR3 induction chemotherapy backbone for childhood relapsed/refractory acute lymphoblastic leukemia. Pediatr Blood Cancer 2016 11;63(11):1943-8



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BACKGROUND: 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.

PROCEDURES: 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.

RESULTS: 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.

CONCLUSION: 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.

Author List

Sun W, Orgel E, Malvar J, Sposto R, Wilkes JJ, Gardner R, Tolbert VP, Smith A, Hur M, Hoffman J, Rheingold SR, Burke MJ, Wayne AS


Michael James Burke MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Combined Chemotherapy Protocols
Child, Preschool
Induction Chemotherapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Retrospective Studies
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a