title: Risk-Benefit Analysis of Pediatric-Inspired Versus Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Protocols for Acute Lymphoblastic Leukemia in Adolescents and Young Adults.
abstract: OBJECTIVE
  To estimate the risk-benefit trade-off of a pediatric-inspired regimen versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) for first-line treatment of adolescents/young adult (AYA; ages 16-39 years) patients with Philadelphia-negative acute lymphoblastic leukemia.
  
  
  METHODS
  Patient outcomes were simulated using a 6-state Markov model, including complete response (CR), no CR, first relapse, second CR, second relapse, and death. A Weibull distribution was fit to the progression-free survival curve of hyper-CVAD-treated AYA patients from a single-center study, and comparable patient data from a retrospective study of pediatric regimen-treated AYA patients were utilized to estimate a relative progression difference (hazard ratio = 0.51) and model survival differences. Health-state utilities were estimated based on treatment stage, with an assumption that the pediatric protocol had 0.10 disutility compared with hyper-CVAD before the maintenance phase of treatment. Total life-years and quality-adjusted life-years (QALYs) were compared between treatment protocols at 1, 5, and 10 years, with additional probabilistic sensitivity analyses.
  
  
  RESULTS
  Treatment with the pediatric-inspired protocol was associated with a 0.04 increase in life-years, but a 0.01 decrease in QALYs at 1 year. By years 5 and 10, the pediatric-inspired protocol resulted in 0.18 and 0.24 increase in life-years and 0.25 and 0.32 increase in QALYs, respectively, relative to hyper-CVAD. The lower quality of life associated with the induction and intensification phases of pediatric treatment was offset by more favorable progression-free survival and overall survival relative to hyper-CVAD.
  
  
  CONCLUSIONS
  Our exploratory analysis suggests that, compared with hyper-CVAD, pediatric-inspired protocols may increase life-years throughout treatment stages and QALYs in the long term.
authors: 1 Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington , Seattle, Washington.
authors: Gregory F
authors: GF
authors: Guzauskas
authors: 2 Jazz Pharmaceuticals , Palo Alto, California.
authors: Kathleen F
authors: KF
authors: Villa
authors: 2 Jazz Pharmaceuticals , Palo Alto, California.
authors: Geertrui F
authors: GF
authors: Vanhove
authors: 2 Jazz Pharmaceuticals , Palo Alto, California.
authors: Vicki L
authors: VL
authors: Fisher
authors: 1 Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington , Seattle, Washington.
authors: David L
authors: DL
authors: Veenstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
keywords: Markov model; acute lymphoblastic leukemia; hyper-CVAD; pediatric inspired; progression-free survival; risk–benefit