The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment‐related mortality and not an increased relapse rate – a population‐based analysis of 25 years of the Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) Study Group

Abstract

The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment-related mortality and not an increased relapse rate -a population-based analysis of 25 years of the Austrian ALL-BFM (Berlin-Frankfurt-M € unster) Study Group SummaryAdolescents aged 15-18 years with acute lymphoblastic leukaemia (ALL) have been historically reported to have a poorer prognosis than younger children. We retrospectively analysed the characteristics and outcome of 67 adolescents included in a population-based series of 1125 non-infant cases that were enrolled into four Austrian ALL-BFM (Berlin-Frankfurt-M€ unster) multicentre trials at paediatric institutions within a 25-year period. Fiveyear event-free survival (EFS) and overall survival (OS) were 66 AE 6% and 76 AE 5% respectively, and thus lower than in younger children (83 AE 1%, 91 AE 1%; P < 0Á001). This was not due to an increased cumulative incidence of relapse (CIR) (5-year CIR: 19 AE 5% vs. 13 AE 1%; P = 0Á284), but due to an increased incidence of treatment-related death [5-year cumulative incidence of death (CID): 15 AE 4% vs. 3 AE 0%; P < 0Á001] as a first event.Furthermore, while 44/67 (66%) non-high-risk adolescents had favourable 5-year EFS and OS rates (76 AE 7%, 89 AE 5%), 18/67 (27%) high-risk adolescents had an inferior outcome (5-year EFS: 56 AE 12%, OS 61 AE 11%, P < 0Á05). Among the latter patients the CID was significantly higher than in younger high-risk children (22 AE 10% vs. 6 AE 2%; P = 0Á020). Given that adolescent age is an independent risk factor for death as a first event, this specific age group may need particular vigilance when receiving intense BFM-type chemotherapy, as relapse-free survival is similar to younger children.

Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia

“…Previously published studies showed that, also in acute lymphoblastic leukemia, adolescents are more fragile than children. [25][26][27] The reasons behind the observation that adolescents have an increased risk for death in CCR are unclear, but they may reflect age-dependent differences in immunologic response to infections and tissue toxicity following chemotherapy.…”

Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols

“…We postulate that the strategy using intensive pediatric chemotherapy while minimizing the indication of HSCT was feasible for adolescent patients with AML. Meanwhile, reports on AYA patients with ALL showed that adverse events such as severe infection, osteonecrosis, thrombosis, and hyperglycemia are generally more problematic in older patients, although the latter three events are associated with an intensive use of corticosteroids and/or asparaginase that are not commonly used in therapies for AML [11][12][13]26]. In fact, previous reports on AYA patients with AML from the St. Jude Children's Research Hospital and COG both showed significantly higher TRD compared to younger AML patients [17,18].…”

Treatment of Pediatric Acute Lymphoblastic Leukemia

“…Young adult patients also experience a higher rate of treatment-related morbidity and mortality, particularly secondary to infection, osteonecrosis, and thrombosis. 30,31 Multiple studies have demonstrated the benefit of treating adolescent and young adult patients with ALL on pediatric-based protocols. 32 …”