Central nervous system (CNS) prophylaxis involving cranial irradiation has frequently been found to result in cognitive deficits in survivors of childhood acute lymphoblastic leukaemia. The existence of this effect is still controversial, however, as is the question of factors that might affect its severity. The literature is surveyed and a meta-analysis undertaken on 30 IQ comparisons, which shows a substantial average decrement in irradiated subjects. The effect is larger when radiation is administered at a younger age and appears to be progressive. The effect may comprise two elements, one common to young cancer patients and one specific to CNS prophylaxis.
To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.
Significant numbers of children and adolescents with acute lymphoblastic leukemia (ALL) do not adequately adhere to their treatment regimen. Failure to take the appropriate amount of prescribed medication may result in disease relapse. Although a number of research studies have sought to identify the factors associated with medication nonadherence in this group, no systematic study has sought to evaluate the efficacy of intervention packages in improving adherence. The aim of the current paper is to provide an overview of the research investigating treatment adherence in ALL patients and to identify the relevant risk factors associated with reduced adherence with medication. The paper will further discuss the role of psychologic therapy in improving treatment adherence in children and adolescents with ALL, with a particular focus on identifying the need for controlled outcome studies.
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