12 Chapter 1 TREATMENT AND SURVIVAL Survival of ALL has increased tremendously over the past decades. In high-income countries, the five-year event free survival rose from around 35% in the 1970’s to more than 90% in current treatment protocols (Figure 2).3,4 This improvement was due to optimization of chemotherapy regimens as well as improved response based risk stratification and supportive care. From 2011 to 2020, children with ALL were treated according to the Dutch Childhood Oncology Group (DCOG) ALL-11 protocol, and the studies described in this thesis were all conducted under this protocol. Cum Overall Survival 1,0 0,8 0,6 0,4 0,2 0,0 time (years) 40 35 30 25 20 15 10 5 0 … DCLSG-ALL1 (1972-1973) DCLSG-ALL2 (1973-1975) DCLSG-ALL3/ALL4 (1975-1978) DCLSG-ALL5 (1978-1983) DCLSG-ALL6 (1983-1988) DCLSG-ALL7 (1988-1991) DCLSG-ALL8 (1991-1997) DCLSG-ALL9/INTERFANT99 (1998-2004) DCOG-ALL10/INTERFANT06/ESPHALL (2004-2012) DCOG-ALL11/INTERFANT06/ESPHALL (2012-2020) Figure 2. DCOG Registration: Outcome ALL 1997-2020 by protocol period Courtesy dr. H. de Groot-Kruseman Treatment in ALL-11 consisted of four phases: induction, consolidation, intensification and maintenance. During induction treatment, patients received high doses chemotherapy and prednisolone. The intensity of treatment after induction therapy was based on therapy response and specific chromosomal abnormalities. In the ALL-11 protocol, patients were stratified to standard, medium or high risk treatment. Medium risk (MR) maintenance treatment plays a key role in this thesis. MR maintenance treatment contained 28 three weekly treatment cycles. Patients received doxorubicin on the first day of the first four treatment cycles, vincristine once every three weeks, methotrexate once per week and 6-mercaptopurine once per day, as well as dexamethasone for five consecutive days at the beginning of each treatment cycle (Figure 3). Depending on randomization, patients also received asparaginase once every three weeks until week 15 or 27 of maintenance treatment. Apart from curative treatment and associated supportive care, standard care includes systematic psychosocial support for both the child and family, support from social work and physical activity recommendations.
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