Innovative approaches of targeted therapy for CML of childhood in combination with paediatric haematopoietic SCT.

Allogeneic haematopoietic SCT (HSCT) induces CRs in most patients with CML. With the excellent short-term treatment results induced by imatinib (IMA), attitudes have changed and only a minority of children are now transplanted upfront. This review addresses the role of IMA in children with CML, focusing on the starting dose of IMA, possible adverse effects, timing of HSCT in children, duration of IMA treatment and monitoring of treatment efficacy to unravel failure of early treatment of IMA as well as treatment of CML relapse after HSCT. As the paediatric experience with IMA is still very limited, many answers and algorithms are adapted from CML in adults. Basically, HSCT should be postponed to achieve an optimal tumour cell reduction by IMA treatment. Children with a low-risk EBMT score should undergo HSCT within 2 years after diagnosis to avoid prolonged exposure and unknown late effects of IMA. Without a perfectly HLA-matched donor, HSCT may be postponed until CML becomes refractory to IMA. As realized in the presently activated international trial CML-paed II, this approach represents a risk-adapted therapy with the benefit of being tailored to the needs and profile of an individual patient.