Pediatria pre prax 1/2020

Acute lymphoblastic leukemia in children with Down syndrome

Down syndrome (DS) is the most common chromosomal abnormality in children and is associated with an increased incidence of acute leukemia. Children with DS are at high risk for developing B-cell precursor acute lymphoblastic leukemia (DS-ALL), with worse treatment results for higher relapse rates and increased treatment-related mortality (TRM), especially for infection. From a biological point of view, it is a heterogeneous group of leukemias that are characterised by lower frequency of typical cytogenetic subgroups of childhood ALL and increased incidence of CRLF2-IL7R-JAK-STAT activating genetic aberrations. The most common cause of treatment failure is the relapse of the disease, so deescalation of chemotherapy intensity might be feasible in 10 % - 15 % DS-ALL patients with prognostically favorable cytogenetic findings (ETV6-RUNX1 and high hyperdiploidy, eventually MRD negativity at the end of induction), where TRM is the major adverse event. TRM due to infections occurs in all phases of treatment, children with DS-ALL require more frequent monitoring throughout treatment and consistent supportive measures. To improve treatment outcomes it is necessary a better understanding of the causes of treatment failure and TRM, the introduction of new treatments that target the unique biological properties of DS-ALL, and the enhancement of supportive measures to reduce the risk od TRM associated with infections. In support of these goals, a prospective DS-ALL registry is planned to be developed on the basis of international cooperation and also to provide recommendations for the supportive treatment od these risk patients. The long-term effort is to develop an international DS-ALL protocol based on analysed data from the registry.

Keywords: acute lymphoblastic leukemia, Down syndrome, childhood