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

Abstract

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.

Treatment of Pediatric Chronic Myeloid Leukemia in the Year 2010: Use of Tyrosine Kinase Inhibitors and Stem-Cell Transplantation

“…Nevertheless, imatinib must currently be considered to be the best front-line treatment for CML, a benefit that should be offered to children 11,[21][22][23][24] The drug was licensed for the use in children by the Food and Drug Administration in 2003. To date, the efficacy and side effects of imatinib have been evaluated in controlled phase I/II trials comprising less than 200 children with Phϩ leukemias and solid tumors.…”

“…While the results of allo-SCT for CML are best in pediatric patients, there are no data with respect to long-term use, and therefore the safety of tyrosine kinase inhibitors (TKIs) in children. 11 This review seeks to provide some guidance as to the appropriate management of CML in childhood.…”

Clinical characteristics and treatment outcome of pediatric patients with chronic myeloid leukemia

“…5,6 While most data regarding the use of imatinib mesylate for chronic myeloid leukemia comes from studies in adult patients, this treatment strategy has now been expanded to include children with Ph + chronic myeloid leukemia. 7,8 However, little information is available regarding response, outcome and toxicity of imatinib mesylate in children. At our institution, we have used this adult-based strategy for children keeping stem cell transplantation as the ultimate treatment of choice when a suitable donor source is available.…”

“…However, the 5-year survival is significantly better for pediatric patients in CP1 following matched sibling donor stem cell transplantation than with alternative donors. 8 Based on such data, our own practice has been to…”

Impact of the type of the BCR-ABL fusion transcript on the molecular response in pediatric patients with chronic myeloid leukemia

“…Hemorrhages are commonly attributed in this leukemia to the frequent diffuse activation of coagulation, hyperfibrinolysis, and non-specific proteolytic activity, [1][2][3][4] and have also been reported to occur before the diagnosis of APL has been made and therapy started.…”