No treatment related mortality in patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) in Dutch Childhood Oncology Group protocols ALL-7 and ALL-8

Abstract

10004 Background: Children with DS have an approximately 12-fold increased risk of developing ALL compared to the general pediatric population. Outcome in patients with DS and ALL is inferior compared to non-DS patients. This may be due to an increased treatment related toxicity and mortality. The purpose of this study was to evaluate our experience with treatment related toxicity in DS children with ALL. Methods: We retrospectively analyzed the medical records of children with ALL who were enrolled on the virtually identical Dutch ALL-7 or ALL-8 protocols between 1988 and 1996. The same protocols were used for DS and non-DS patients, without a priori treatment modifications for DS patients. Results: Among 685 children with de novo ALL, 16 (2.3%) patients had DS. Three of these patients were not treated according to protocol because of physicians or parents’ choice and were excluded from this analysis. Mean age at diagnosis was 6.5 years (range 2.6 to 15.8 yrs). One patient died during induction treatment as a consequence of an acute cardiac event, which did not appear to be chemotherapy related. Serious toxicity, requiring treatment modification according to protocol guidelines, occurred in 8 of the remaining 12 patients (66.7%). None of the patients died as consequence of treatment related toxicity. Four patients had a relapse, in one case 18 yrs after the initial diagnosis. Event free survival (EFS) after 10 yrs was 69% in DS patients compared to 72.6 % in non-DS patients. Relapse rather than toxic mortality was the first event in patients with DS treated according to Dutch ALL-7 and ALL- 8 protocols. Conclusions: These data do not support an a priori reduction of ALL treatment in children with DS. Dose modification according to traditional guidelines appears adequate. The balance between efficacy and toxicity may be different when more intensive treatment regimens are used in children with DS. No significant financial relationships to disclose.