Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004
The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin–Frankfurt–Münster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (P<0.001) and from 78.7 to 86.4% (P=0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC >100 × 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.