Anders Öberg: Aspects of physical capacity after hematopoietic cell transplantation in childhood

Abstract

Advances in pediatric oncology over recent decades have resulted in substantial improvements in survival, with the majority of children diagnosed with cancer now becoming long-term survivors. Consequently, increasing attention has been directed toward the late effects of cancer treatment and their impact on long-term health.

For children with high-risk or relapsed hematological malignancies, hematopoietic cell transplantation (HCT), with or without total body irradiation (TBI), represents a potentially curative treatment. Although highly effective, these intensive treatment regimens are associated with an increased risk of late complications affecting multiple organ systems.

This thesis evaluated long-term physical performance, cardiopulmonary function, body composition, endocrine function, and frailty in young adults treated with HCT during childhood.

HCT survivors demonstrated significantly reduced exercise capacity and aerobic fitness, reflected by lower maximal workload and peak oxygen uptake. Cardiopulmonary exercise testing indicated that impairments in both cardiac and pulmonary function contributed to the reduced exercise performance, despite conventional resting echocardiographic parameters remaining within the normal range.

Survivors also exhibited altered body composition, characterized by reduced skeletal muscle mass and increased adiposity despite normal body mass index, underscoring the limitations of routine clinical assessments for these survivors. These findings are consistent with sarcopenic obesity, a phenotype associated with adverse metabolic outcomes and increased risk of premature mortality.

Furthermore, a high prevalence of frailty and pre-frailty was observed. Frailty, defined by features including reduced muscle mass and strength, fatigue, low physical activity, and impaired physical performance, affected more than one-third of survivors, while nearly half fulfilled criteria for pre-frailty. Frailty was associated with longer time since transplantation, older age at follow-up, and lower vitamin D values, whereas no significant associations were identified with previous TBI exposure, cumulative chemotherapy doses, growth hormone status, or markers of chronic inflammation.

Collectively, these findings demonstrate that childhood HCT is associated with persistent impairments across multiple physiological systems that may not be detected by routine clinical assessments. The results support the need for lifelong, multidisciplinary follow-up incorporating comprehensive evaluation of physical function, cardiopulmonary health, body composition, endocrine status, and modifiable risk factors to facilitate early intervention and optimize long-term health outcomes in HCT survivors.