The assessment of short-term growth in children on cytotoxic chemotherapy

This thesis consists of two groups of prospective short-term studies; the first group evaluates the technique of knemometry and lower leg length (LLL) changes in a group of healthy children and adults; the second group of studies is based on short-term anthropometric changes in children on treatment for acute lymphoblastic leukaemia (ALL). Studies in the healthy group were performed on 26 prepubertal children and 9 young adults. The first study refined the technique of knemometry by minimizing intra-observer bias; despite reducing bias knemometry remained a highly precise form of measuring changes in LLL. The next study in this group of subjects showed the presence of significant intradaily variation in the LLL of some fully grown adults and the influence of change in body weight and oedema on LLL. There was no distinct pattern of lower leg changes in these children when followed up for a period of 12 weeks by weekly measurements or when followed up daily for a period of 4 weeks. The growth pattern was non-linear in nature and the daily changes were not statistically related to nocturnal urinary growth hormone (uGH) excretion, a non-invasive marker of growth hormone secretion. Studies of short-term growth in ALL were performed on 25 children 14 of whom had knemometry during the two year protocol for a median duration of 56 weeks. Conventional anthropometric studies as well as knemometry showed an adverse effect of intensive chemotherapy(CT) on growth. The effects on growth seemed to be transient with evidence of catch-up growth during less intensive periods of CT. Lower leg growth during continuation CT was comparable to that seen in healthy children and fluctuations in growth were associated with changes in neutrophil counts. The sitting height:height ratio reduced temporarily over the period of remission induction and although the initial deceleration in LLL improved immediately after induction, total axial growth took longer to improve suggesting a transient but disproportionately greater adverse effect of CT on the vertebral spine. A study of biochemical markers of bone and collagen turnover in 16 subjects over the first six months of CT showed changes consistent with catch-up growth and similar to that found by knemometry. An uncoupling of bone turnover favouring bone degradation during the intensive phases of CT and favouring bone formation during the phase of catch-up growth was also evident. Studies of uGh, insulin-like growth factor-I(IGF-I) and IGF Binding Protein-3(IGFBP-3) in the 8 subjects who had knemometry showed a possibility of a state of partial growth hormone resistance at presentation and during the first few weeks of CT where IGF-I and IGFBP-3 levels were not raised despite high uGH excretion. Catch-up growth, observed as a supraphysiologically high LLL velocity, occurred in the presence of high uGH levels and normal IGF-I and IGFBP-3 levels suggesting that catch-up growth might be partly independent of GH/IGF-I action.