Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children with down syndrome

Abstract

Background. Acute lymphoblastic leukemia (ALL) in children with Down syndrome (DS) presents with an increased incidence, higher frequency of adverse effects and inferior probability of survival. Attempts at improving outcomes face the dilemma posed by the need to avoid excessive toxicity while maintaining the efficacy of treatment. Dose reductions and avoidance of infusions of intermediate and highdose methotrexate are common in this group. Procedure. In a matched pair analysis we compared adverse effects and survival after ALL chemotherapy using intermediate and high doses of methotrexate in children with and without Down syndrome. Results. Following intermediate and high doses of methotrexate to treat primary ALL, children with DS did not require opiate analgesia and parenteral nutrition for severe mucositis more often than children without DS. Children with DS spent more days in hospital and missed more doses of maintenance chemotherapy. Chemotherapy dose reductions were common and in this study had no detectable adverse impact. Event-free and overall survival (OS) of children with ALL was lower in the DS than the non-Down syndrome (NDS) control group. The difference, however, was no longer significant during the recent treatment era. Conclusions. The feasibility of all treatment elements that are efficacious in pediatric ALL needs to be carefully considered in children with DS. In addition to survival data, the prospective collection of data on both adverse events and treatment modifications is essential to strike a balance between the avoidance of adverse effects and the need for intensive therapy that will safely improve ALL outcomes in this group.

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003

“…6,[19][20][21][22] However, both TRM and IRM appear slightly higher in our cohort than in other trials. A recent retrospective analysis by the Ponte di Legno group of 653 DS-ALL patients treated on various protocols found a 2-year TRM of 7%, which is lower than that seen on UKALL 2003 (5-year cumulative incidence of TRM 21.6%).…”

“…19,20 This may in part be a result of heightened methotrexate sensitivity and reduced renal clearance of methotrexate. 23,24 In addition, a recent report found an association between hyperglycemia and episodes of sepsis during the induction period on the UKALL 2003 trial, particularly in patients with DS.…”

Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome

“…[23][24][25]33 Historically, Down syndrome ALL (DS-ALL) has been associated with inferior outcome, both with regard to OS and EFS. 34,35 In this study, DS-ALL was associated with very poor outcome, irrespective of the time period (early vs. late period) and the fact that most of these patients were stratified as standard-risk.…”

Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia

“…2,16,24 In our study, a significantly higher proportion of children with DS experienced methotrexate-induced gastrointestinal toxicity compared with the non-DS controls, which is consistent with other reports. 2,16,24,25 Dose reductions were applied both in anticipation of possible toxicity, and because of apparent excessive toxicity, and were restricted to DS patients only. However, due to excessive toxicity both DS-ALL patients (n=3) and one non-DS-ALL patient, each received one course less than required per protocol.…”