Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia in Adolescents and Young Adults

Amy Y. Wang, MD, MPH; Lori S. Muffly, MD, MS; Wendy Stock, MD

Disclosures

J Oncol Pract. 2020;16(5):231-238. 

In This Article

Front-line AYA all Regimens

The discourse on treating AYAs via a pediatric versus adult ALL regimen first began when retrospective studies from various countries demonstrated superior outcomes when AYAs were treated according to a pediatric protocol.[12–16] These observations spurred several prospective multicenter trials conducted by both pediatric and adult oncologists that either incorporate pediatric-inspired strategies or fully adopt pediatric protocols,[17–20] which are reflected in the current National Comprehensive Cancer Network Guidelines (Table 2).[13,17,19–25]

One of these studies, CALGB 10403, focused exclusively on patients in the AYA age range. The trial used identical dosing and schedule from one arm of the Children's Oncology Group study AALL0232, which is an augmented Berlin-Frankfurt-Munster regimen, and enrolled 318 patients age 17 to 39 years from 2007 to 2012.[21] The study recently reported the regimen was feasible to administer to AYAs in adult oncology clinics as well as effective, with a 3-year event-free survival (EFS) and overall survival (OS) of 59% (95% CI, 54% to 65%) and 73% (95% CI, 68% to 78%), respectively.[21] Median EFS was 78.1 months (95% CI, 41.8% to not reached), as compared with a historical control of 30 months (95% CI, 22% to 38%).

One notable exception to the use of a benefit to a pediatric regimen in AYAs was a single-institution study comparing outcomes after hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a common regimen administered to patients with ALL by adult oncologists, to augmented Berlin-Frankfurt-Munster, with no difference detected in 5-year complete remission duration (55% v 53%; P = .98) or OS (60% v 60%; P = .99).[23] Despite this observation, the available data increasingly support the use of pediatric-inspired regimens to treat AYAs.

It is believed that the increased intensity of pediatric regimens may be responsible for the noted gains in survival. Pediatric protocols use higher cumulative doses of asparaginase, vincristine, and steroids; incorporate delayed intensification into the treatment schema; and provide more intensive CNS prophylaxis.[12,21] In addition to increased intensity of therapy, pediatric-based regimens offer a lower cumulative dose of alkylators, anthracyclines, and cytarabine, which result in fewer long-term adverse effects, particularly infertility.[26] However, asparaginase therapy in pediatric regimens carries a higher risk of hepatic, pancreatic, and thrombotic complications, and the risk is increased in older or obese patients.[18,19,21,25,27] CALGB 10403 and other pediatric regimens are typically more complex than many adult regimens and may be challenging to administer outside of a center with larger volume and a support staff familiar with the largely outpatient administration of these regimens.[26] This may explain the findings that the adoption of pediatric-inspired regimens among adult oncologists has been slow; one population-based study demonstrated that as of 2014 only one-third of AYAs with newly diagnosed ALL were being treated according to pediatric-inspired protocols.[28]

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