Toxicity of ALL Treatment in Adolescents as Compared to That in Younger Children.

Introduction: The results of therapy in young adults and adolescents with ALL has reported to be better if more aggressive pediatric treatment regimens were applied as compared to regimens more commonly used in adults (E.g. deBont, ASH 2003; Boissel, JCO 2003). A point of concern in applying pediatric regimens in young adults is the possible toxicity of these regimens. To address this, we retrospectively evaluated the toxicity of childhood ALL regimens in younger children as compared to older children and adolescents.

Patients: 90 patients treated for ALL in our hospital between 1985 and 2003 were included in the study. Treatment consisted of ‘classical’, multi-agent, pediatric regimens of the Dutch Childhood Oncology Group and the I-BFM, and included dexamethasos (n=47) or prednison (n=4) during induction and maintenance therapy in the majority of the patients. The survival and toxicity data of 66 children aged 3 to 9 years (mean 6 +/− 1 year) were compared with those in 24 children aged 13 to 17 (mean 15 +/− 1 year). Toxicity analysis included infectious complications, renal and liver function, bone density and occurrence of diabetes.

Results: As expected, as older age is a risk factor in childhood ALL, survival was better in the younger group (87% vs. 67%), although the survival in the older group is still better than in most adult-studies (Boissel, JCO 2003, deBont, ASH 2003). Older children showed more corticosteroid-related toxicity: Insulin-dependant hyperglycemia occurred in 25% of older patients, as compared to 0% in the younger group. Also, bone-density was significantly more reduced in patients treated with dexamethason-including maintenance treatment in older patients (Z-score of -2.8) as compared to the younger patients (Z-score of -1.5) at the end of treatment. No differences in renal and liver toxicities were seen between the two groups. Fever with neutropenia occurred more often in the younger patients (NS), and also treatment delay was more often necessary in the younger patients.

Conclusion: Childhood-ALL regimens are regarded as possible beneficial in older patients as compared to ‘adult regimens’. However, major concern is the possible toxicity of these pediatric regimens. Our data show that toxicity of these aggressive regimens is similar in older children/adolescents as compared to the toxicity in younger children. Only reversible corticosteroid-induced toxicity was more prominent in older patients, other toxicities were similar or even less in older patients. These data suggest that ‘pediatric regimens’ are well-tolerable in older patients with ALL.