Adolescent and Young Adults with Acute Lymphoblastic Leukaemia Benefit from Treatment in a Paediatric Setting or NCI-Designated Cancer Centre

Poorer survival was observed in AYA ALL patients treated in adult settings

Adolescent and young adults (AYAs) with acute lymphoblastic leukaemia (ALL) achieved superior survival benefit when treated with paediatric ALL regimens in paediatric settings compared with adult ALL regimens administered in an adult institution, according to a retrospective analysis currently appearing in Blood Advances, the Journal of the American Society of Hematology. 

AYAs aged 15-39 years with ALL may receive care in either paediatric or adult cancer settings; however, superior overall survival (OS) was observed in AYA ALL patients receiving front-line treatment in a pediatric compared to an adult setting (hazard ratio [HR], 0.53, 95% confidence interval [CI], 0.37-0.76 or at an National Cancer Institute (NCI)/Children’s Oncology Group (COG) centre compared with an adult setting (HR, 0.80; 95% CI, 0.66-0.96). 

Statistically significant superior leukaemia-specific survival (LSS) was also observed by multivariate analysis with AYAs receiving ALL care in a paediatric setting (HR = 0.51, 95% CI, 0.35-0.74) or a NCI/COG facility (LSS HR = 0.80, 95% CI, 0.65-0.97) versus an adult setting, respectively. 

Dr Lori Muffly, medical oncologist at Stanford Health Care in Palo Alto, USA and colleagues investigated the patterns of care and outcomes in AYAs with ALL using the California Cancer Registry between 2004 and 2014. They assessed sociodemographics, treatment location, and front-line therapies administered to AYAs diagnosed with ALL during this time period and used Cox regression models to determine the association of ALL treatment, institutions, and regimens with OS and LSS for the entire cohort of AYAs aged 15 to 39 years, a younger cohort of AYAs defined as <25 years, and AYAs treated in the adult cancer setting only. 

AYA cancer care is highly variable with many patients receiving adult cancer regimens in an adult facility, despite recommendations advising a paediatric approach 

AYAs with ALL are often caught in the gap between paediatric and adult cancer care and may be referred to receive treatment at either an adult or a paediatric cancer centre. Furthermore, if treated at an adult centre, an AYA patient with ALL may receive a paediatric or adult ALL first-line treatment regimen, even though numerous review articles, society guidelines, and AYA cancer resources espouse the paediatric approach.

The 1473 patients in this analysis had a median age at diagnosis of 22 years; 32.3% were aged 15 to 18 years, and 56.8% were less than 25 years. Two-thirds of the cohort was male and 63.7% were of Hispanic race/ethnicity. 

The majority (67.7%) of patients were treated in an adult cancer setting. Of patients treated in adult settings, just one fourth (24.8%) received a front-line pediatric ALL regimen, and 40.7% were treated at NCI-designated centre. The treatment setting differed significantly by age, with 86.9% and 16.0% of AYA aged 15 through 18 and 19 through 24 years, respectively, treated in a pediatric setting, and >98% of AYA aged 25 through 39 years were treated in an adult setting (p < 0.001). 

The proportion of AYAs treated in a pediatric setting increased significantly during the study period, at 27.3% from 2004 through 2007, to 34.9% from 2012 through 2014 (p = 0.002). 

AYAs have similar outcomes with either adult or paediatric first-line treatment when treated at an adult facility 

In AYAs being treated in an adult facility, delivering a front-line treatment tailored to paediatric patients did not improve survival. Outcomes for AYAs treated in an adult setting did not differ following front-line pediatric or adult ALL regimens; there was no significant difference in OS (HR, 0.83; 95% CI, 0.58-1.20) or LSS (HR, 0.99; 95% CI, 0.66-1.47) among AYA receiving adult regimens consisting of hyper-cyclophosphamide, vincristine sulfate, adriamycin, and dexamethasone versus to pediatric ALL regimens.  

Conclusions 

These findings reveal a significant survival advantage for AYA ALL is associated with treatment in a pediatric, as opposed to an adult cancer setting, suggesting that front-line treatment of AYA ALL at paediatric and/or NCI/COG-designated cancer centres should be considered for all AYA patients. 

The long-term survival benefit of pediatric ALL regimens delivered in an adult cancer setting was limited by short median follow-up time of 2.3 years for surviving patients. Also, the investigators were unable to reliably track sequential therapies, such as haematopoietic cell transplantation and their influence on outcomes. 

Disclosure 

No external funding was disclosed.

Reference 

Muffly L, Alvarez E, Lichtensztajn D, et al. Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukaemia: a population-based study. Blood Advances 2018; 2:895-903. doi: https://doi.org/10.1182/bloodadvances.2017014944