Читать книгу Blood and Marrow Transplantation Long Term Management - Группа авторов - Страница 136

Growth in children and the attainment of normal adult height is a complex process that requires balanced nutritional, genetic, endocrine, and other physical and psychosocial factors. During infancy, growth is highly dependent on nutrition and thyroid hormone. During childhood, hGH predominates and, in puberty, the synergistic interplay of hGH and sex steroids is critical for attainment of final adult height. During all stages, any prolonged disturbance of physical or psychosocial well‐being may adversely impact growth and development [93,94]. For the child with cGVHD such disturbances may include delayed hormonal and direct skeletal effects of pretransplant TBI ± cranial irradiation, chronic glucocorticoid therapy >5mg/m²/day [95,96] and phases when GVHD activity is inadequately controlled. Excessive glucocorticoid doses may cause pubertal delay by inhibiting release of gonadotropins or directly inhibiting secretion of sex steroids, but primary gonadal failure can also occur secondary to conditioning.

The monitoring approach is to, at least annually, plot height, height‐velocity, weight annually on age/gender‐appropriate (and sometimes disease‐specific) growth charts, along with Tanner staging to assess pubertal status. Bone age is followed in growing children to assess skeletal maturity and growth potential while children progress towards final adult height. Referral to pediatric endocrinology is advised if a child is falling off their height percentile channel and/or not entering puberty at the usual time. Coordination of testosterone or estrogen therapy for pubertal delay must be carefully coordinated with hGH therapy so that premature closure of epiphyses and compromise of final adult height is avoided. Issues to note are that there is no threshold dose of glucorticoids above which response to hGH clearly and predictably declines. However, the best growth responses to hGH appear to occur when prednisone is dosed at ≤0.5 mg/kg/once daily on alternate‐days [97,98]. A reasonable approach is to wait until prednisone therapy is at every‐other‐day dosing or at least <5 mg/m²/day before hGH testing and/or replacement therapy are undertaken. HCT survivors who received TBI ± CNS radiation showed an unfavorable profile of inflammation (higher IL‐6), adipokines (higher leptin and lower adiponectin), and sarcopenic obesity (higher percent fat mass and lower lean body mass per DEXA scan) compared to sibling controls despite having similar BMI [99,100]. Increasing lean body mass may represent a tangible target for mitigating high cardiometabolic risks of HCT survivors. Interestingly, obese prepubertal boys who received 6 months of hGH, without additional dietary or exercise modifications, experienced a 5% increase in lean body mass which lends support to the hypothesis that hGH may provide other benefits in addition to promoting height growth [101].