Imatinib treatment and longitudinal growth in pediatric patients with chronic myeloid leukemia: influence of demographic, pharmacological, and genetic factors in the German CML-PAED cohort.

In children and adolescents, impaired growth due to tyrosine kinase inhibitor therapy remains an insufficiently studied adverse effect. This study examines demographic, pharmacological, and genetic factors associated with impaired longitudinal growth in a uniform pediatric cohort treated with imatinib. We analyzed 94 pediatric patients with chronic myeloid leukemia (CML) diagnosed in the chronic phase and treated with imatinib for >12 months who participated in the Germany-wide CML-PAEDII study between February 2006 and February 2021 (clinicaltrials gov. Identifier: NCT00445822). During imatinib treatment, significant height reduction occurred, with medians of -0.35 standard deviation score (SDS) at 12 months and -0.76 SDS at 24 months. Cumulative height SDS change (Δ height SDS) showed a more pronounced effect in prepubertal patients during the first year but were similar between prepubertal and pubertal subgroups by the second year (-0.55 vs. -0.50). From months 12 to 18 on imatinib, only 18% patients achieved individually longitudinal growth adequate to the growth standard (Δ height SDS ≥0). When patients were divided into two subgroups based on median Δ height SDS (classifier Δ height SDS > or ≤-0.37) after 1 year on imatinib therapy, cohort 1 (Δ height SDS ≤-0.37) showed younger age at diagnosis, a higher proportion of prepubertal children, but also better treatment response and higher imatinib serum levels. Exploring the association of growth parameters with pharmacokinetically relevant single nucleotide polymorphisms, known for affecting imatinib response, showed no correlation. This retrospective study provides new insights into imatinib-related growth impairment. We emphasize the importance of optimizing treatment strategies for pediatric patients to realize their maximum growth potential.

On the relationship between children's perspective taking in complex scenes and their spatial drawing ability.

Depicting space and volume in drawings is challenging for young children in particular. It has been assumed that several cognitive skills may contribute to children's drawing. In the present study, we investigated the relationship between perspective-taking skills in complex scenes and the spatial characteristics in drawings of 5- to 9-year-olds (N= 121). Perspective taking was assessed by two tasks: (a) a visual task similar to the three-mountains task, in which the children had to select a three-dimensional model that showed the view on a scene from particular perspective and (b) a spatial construction task, in which children had to plastically reconstruct a three-dimensional scene as it would appear from a new point of view. In the drawing task, the children were asked to depict a three-dimensional scene exactly as it looked like from their own point of view. Several spatial features in the drawings were coded. The results suggested that children's spatial drawing and their perspective-taking skills were related. The axes system and the spatial relations between objects in the drawings in particular were predicted, beyond age, by certain measures of the two perspective-taking tasks. The results are discussed in the light of particular demands that might underlay both perspective taking and spatial drawing.