Abstract
BACKGROUND: Adolescents and young adults (AYA: 15-39y) with acute lymphoblastic leukemia (ALL) have inferior survival when compared with children (1-14y). A comprehensive approach that examines the contribution of sociodemographics, clinical prognosticators, and treatment approach (pediatric vs. adult-inspired) in a real-world setting, is lacking.
METHODS: We assembled a retrospective cohort of184 patients diagnosed with ALL at age 1-39y and treated at a single institution between 1990 and 2010, irrespective of clinical trial enrollment. Medical record abstraction yielded sociodemographics, clinical prognosticators, treatment approach, and duration of treatment phases (induction, consolidation, maintenance). We divided follow-up time into one-month blocks and constructed a discrete-time dataset which allowed for monthly updates of duration of treatment, time from remission, and time from end of treatment. Logistic regression with a complementary log-log link was used to model relapse risk, with death and hematopoietic cell transplantation as censoring events. We examined risk of relapse at two points: i) relapse on therapy; ii) relapse after completing therapy. Multivariable models examined differences in relapse risk between AYA and children, adjusting for gender, race/ethnicity, WBC at diagnosis, time to remission, duration of maintenance and duration of consolidation. Oncology service (medical vs. pediatric) and therapy type (adult vs. pediatric-inspired) were combined to create the following variable: medical oncology + adult therapy; pediatric oncology + pediatric therapy; mixed oncology and/or mixed therapy. Socioeconomic status (SES) and payor were combined to create the following variable: low SES + public insurance; high SES + private insurance; other.
RESULTS: The cohort included 91 children (median age: 4y; interquartile range [IQR] 3-10y) and 93 AYA (median age: 23y; IQR 19-30y). There were no differences between children and AYA with respect to sex (p=0.4), race/ethnicity (p=0.1), payor (p=0.2), SES (p=0.2) or WBC (p=0.3). Overall, 19% of the AYA were treated with pediatric-inspired therapy and 18% received treatment by pediatric oncology services; of the 15-21y AYA, 41% received treatment by pediatric oncology and 44% with pediatric-inspired therapy (no 22-39y received pediatric therapy). AYA had inferior 5y-relapse-free survival when compared with children (31% vs. 74%; p<0.001) [Fig.1]. AYA also suffered relapses earlier than children [Fig.2]. Risk of on-therapy relapse: A larger proportion of AYA relapsed on therapy (48%) as compared to children (17%, p<0.001), resulting in a 5.9-fold increased risk of relapse for AYA (HR=5.9, 95%CI, 3.2-11.2, p<0.001) when compared with children. In multivariable analysis, the increased risk of relapse in AYA was mitigated (HR=3.1, p=0.02); factors independently associated with on-therapy relapse included treatment with adult-inspired therapy by medical oncology service (HR=2.8, p=0.02). Risk of relapse after completion of therapy: A larger proportion of AYA (47%) relapsed after completing therapy as compared to children (13%, p<0.0001), resulting in a 4.3-fold increased risk of relapse (HR=4.3, 95%CI, 2.1-8.6, p<0.001). The duration of maintenance was shorter in AYA patients who relapsed (median 23.5 mos.) when compared with those who did not relapse (median 29.0 mos.; p<0.01); in children there were no differences in maintenance duration by relapse status (p=0.7). In multivariable analysis, AYA remained at a higher risk of relapse (HR=4.8, 95%CI, 1.6-13.9, p=0.004). Factors independently associated with relapse included duration of maintenance (HR=0.87, 95%CI, 0.8-0.9, p<0.001) and low SES + public insurance (HR=3.9, 95%CI, 1.2-12.7, p=0.02).
CONCLUSIONS: AYA with ALL have poor outcomes when compared with children. The higher risk of early relapse in AYA is explained (in part) by adult-inspired treatment delivered on medical oncology services. Shorter duration of maintenance therapy is associated with risk of relapse after completion of therapy, along with low SES and public payor status. These findings highlight the importance of providing adequate social support to ensure completion of treatment, as well as the role for pediatric-inspired treatment and duration of maintenance treatment in ensuring durable remissions in children and AYA with ALL.
No relevant conflicts of interest to declare.
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