Risk–Benefit Analysis of Pediatric-Inspired Versus Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Protocols for Acute Lymphoblastic Leukemia in Adolescents and Young Adults

Risk–Benefit Analysis of Pediatric-Inspired Versus Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Protocols for Acute Lymphoblastic Leukemia in Adolescents and Young Adults
This study aimed to estimate the risk–benefit trade-off of a pediatric-inspired regimen compared with hyper-CVAD for first-line treatment of AYA patients with Philadelphia-negative ALL. A quantitative evaluation of the risks and benefits of pediatric versus hyper-CVAD therapy in AYA ALL patients may provide useful guidance for patient-specific treatment decisions and development of treatment guidelines.
This was a retrospective analysis of two studies already published and comparison between the two. This exploratory analysis seems to be the first comparative quantitative assessment of the potential benefits and harms associated with a pediatric-inspired protocol versus a hyper-CVAD protocol for the treatment of Philadelphia-negative AYA ALL
This analysis used a 6-state Markov model to evaluate the risks and benefits of using a pediatric-inspired protocol compared with hyper-CVAD. Patients could transition among the health states at intervals of 1 month, with a total time horizon of 10 years. Patients modeled for the hyper-CVAD protocol were from a single-center, long-term, follow-up study of hyper-CVAD in 288 patients, of whom 17% were Philadelphia chromosome–positive. For the pediatric protocol, comparable patient data were used from a retrospective study of 85 patients treated with a pediatric-inspired regimen (modified Dana Farber Cancer Institute pediatric protocol (DFCI 91-01)). The primary outcomes were total life-years and total quality-adjusted life-years for each regimen.
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.
The authors chose these two studies after systematic literature review because they assessed that they were the most comparable in regard to patient characteristics. However, patients' characteristics were not the same in all respects. Also, they had to make assumptions regarding outcomes in Philadelphia-negative patients, since the hyper-CVAD source included Ph-positive patients. Finally, they didn't compare pediatric-inspired protocol to augmented hyper-CVAD. So the conclusion of the study can bias in favor of pediatric-inspired study.
In the absence of randomized controlled trials comparing these two types of protocols, this retrospective analysis suggests that, compared with hyper-CVAD, pediatric-inspired protocols may increase life-years throughout treatment stages and QALYs in the long term. However, it does not compare pediatric-inspired to augmented hyper-CVAD. It seems to support the use of "more intense" regimens for AYA in order to achieve better outcomes even if there is a higher risk of complications during treatment.

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