[Treatment strategy for myeloid leukemia with Down syndrome]

Myeloid leukemia with Down syndrome (ML-DS) demonstrates unique characteristics such as the predominance of FAB M7, an age predilection during the first 4 years of life, and higher sensitivity to chemotherapeutic agents, which translate into a good treatment response as well as increased treatment-related toxicities. Consequently, patients with ML-DS have traditionally been treated separately from non-DS acute myeloid leukemia (AML) children. The 3-year event-free survival rates in recent clinical studies in the Western countries and Japan are all more than 85%. In Japan, two studies (AML-D05 and AML-D11) were conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group. The efficacy of risk-oriented therapy according to morphological response was evaluated in the AML-D05 study. Despite that a dose reduction of chemotherapeutic agents could be performed in many cases, the overall outcome was comparable with those of previous Japanese studies. In the subsequent AML-D11 study, the role of minimal residual disease (MRD) was evaluated. MRD by flow cytometry (FCM) and targeted deep sequencing of GATA1 following the initial induction therapy were significant prognostic factors for predicting relapse. Dose modification according to the end-of-induction FCM-MRD is being attempted in the ongoing JCCG AML-D16 study.