To comprehensively document both acute and late toxicity events in a cohort of patients undergoing a modern risk-stratified chemotherapy schedule (UKALL 2003) for acute lymphoblastic leukaemia (ALL). We aimed to identify predictors of acute (ATE) and late (LTE) toxicity events and to relate the number and nature of ATE with LTE.
Patients aged 1–24 years, diagnosed with ALL (October 2003–June 2011) enrolled in the UKALL 2003 trial from a single centre were included. Patients with Philadelphia-positive ALL, relapsed ALL or who underwent Stem Cell transplant were excluded. Clinicopathological characteristics, treatment regimes, ATE and LTE were collated from SAE reports and patient records. X2 tests were used to identify predictors of ATE and LTE, and Wilcoxon Signed Rank Test to correlate ATE with LTE (IBM SPSS StatisticsV22).
A total of 112 patients were analysed, there were 4 deaths during treatment (sepsis (n = 3) and necrotising leucoencephalopathy (n = 1)). The median age (range) at review was 12 (6–24.9) years. The median (min-max) follow up period was 4.12(1–8.75) years after completion of treatment. ATE and LTE were recorded in 71(63.3%) and 61(58.0%) individuals respectively. NCI risk (p = 0.048), and more intensive regimen allocation (p = 0.014) were significant predictors of ATE. Furthermore, age at diagnosis (p = 0.034), gender (p = 0.004), NCI risk (p = 0.026), clinical risk (p = 0.008), regimen allocation (p = 0.021) and ATE (p = 0.003) were significant predictors of LTE. Although the frequency of LTE was significantly less than ATE (Z=-2.643, p = 0.008), we observed a substantial burden of late-effects. As expected, the pattern of LTE differed from ATE, with decreases in gastrointestinal (p = 0.003) and infective (p < 0.05) events, and increases in neurological (p = 0.038), cognitive (p = 0.001) and psychosocial (p < 0.05) problems. There was a trend for increased LTE in patients receiving 2 vs. 1 delayed intensification (73.8% vs. 51.6%) although this did not reach statistical significance in our relatively small cohort.
Survival following Childhood ALL has improved tremendously which necessitates long-term follow up to identify treatment-associated late morbidity. This study identified predictors of ATE and LTE, and documented the natural history of acute toxicities over time. However a larger multicentre review is required to assess the impact of treatment reduction on the incidence of LTE.
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