Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: results from NOPHO-AML 2004

Abstract

T reatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first induction course of NOPHO-AML 2004 (n=318). Toxicity following induction and consolidation courses (n=6) was analyzed. The probabilities of toxicity and death were determined using time-to-event analyses with Cox multivariate proportional hazard regression for comparative analyses. Age 10-17 years was associated with sepsis with hypotension [hazard ratio 2.3 (95% confidence interval 1.1-4.6)]. Being overweight (>1 standard deviation) was associated with requiring supplemental oxygen [1.9 (1.0-3.5)]. The 5-year event-free and overall survival were 47% and 71%. Children aged 10-17 years showed a trend for inferior 5-year overall survival compared to children aged 2-9 (64% vs. 76%; P=0.07). Infants showed a trend for superior 5-year event-free survival (66% vs. 43%; P=0.06). Overweight children aged 10-17 years showed a trend for superior survival [5-year event-free survival 59% vs. 40% (P=0.09) and 5-year overall survival 78% vs. 56% (P=0.06)] compared to healthy weight children aged 10-17 years. In conclusion, children aged 10-17 years and overweight children had a higher risk of grade 3-4 toxicity. Children aged 10-17 years showed inferior survival, but, unexpectedly, in this age group overweight children tended to have increased survival. This suggests different pharmacokinetics of chemotherapeutic drugs in adolescents and warrants further studies.

Response‐guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML‐01

“…Only four patients stopped treatment due to toxicity, two of whom died. The documented toxicity is in line with other AML treatment schedules . Recently, analysis of the NOPHO‐AML 2004 trial showed that an older age or being overweight was associated with increased toxicity.…”

“…Recently, analysis of the NOPHO‐AML 2004 trial showed that an older age or being overweight was associated with increased toxicity. More insights into pharmacokinetic differences between older versus younger age or infants might be needed to guide optimal dosing in the future …”

Strategies for reducing the treatment‐related physical burden of childhood acute myeloid leukaemia – a review

“…Acute severe treatment-related toxicity grade 3 and/or 4 is observed in about 90% of all patients with AML (Gamis et al, 2014;Lohmann et al, 2016). Acute severe treatment-related toxicity grade 3 and/or 4 is observed in about 90% of all patients with AML (Gamis et al, 2014;Lohmann et al, 2016).…”

Use of granulocyte colony‐stimulating factor and risk of relapse in pediatric patients treated for acute myeloid leukemia according to NOPHO‐AML 2004 and DB AML‐01

“…Treatment for pediatric acute myeloid leukemia (AML) is highly toxic and 5‐10% of patients die as a consequence of treatment . Infections during neutropenia are the most frequent cause of treatment‐related mortality and a major cause of morbidity . Granulocyte colony‐stimulating factor (G‐CSF) has been used to decrease time with neutropenia, aiming to reduce severe infections and treatment‐related mortality.…”