Pubertal growth in young adult survivors of childhood leukemia.

Abstract

Purpose:To determine the effect of cranial irradiation (18 Gy and 24 Gy) on pubertal growth in young adult survivors of childhood acute lymphoblastic leukemia (ALL).Patients and Methods: Final height (FH) and pubertal growth were retrospectively examined in 142 young adult survivors of childhood ALL. All were in first remission and had received either 18 or 24 Gy of cranial irradiation. Eighty-four children (48 girls) were treated with 24 Gy and 58 (35 girls) with 18 Gy. None had received either testicular or spinal irradiation. Timing and duration of puberty were studied in 110 patients.Results: Significant reduction in height standard deviation score (SDS) from diagnosis to FH was seen in both sexes and in both dose groups. In girls, in both dose groups, mean age at peak height velocity (PHV) and A CUTE LYMPHOBLASTIC leukemia (ALL) is the most common childhood malignancy, with an incidence of 3.5 per 100,000. Survival rates for children with ALL have improved enormously over the last 20 years, such that 70% of children can now expect to be longterm survivors with current therapy.', 2 Since 1970, this has in part been achieved by the introduction of treatment directed at the CNS, with a combination of cranial irradiation and intrathecal methotrexate. 3 Until 1980, the dose of cranial irradiation given was 24 Gy (usually administered in 15 fractions over 3 weeks). This was reduced to 18 Gy (administered in 10 fractions over 2 weeks) in 1981 in an attempt to reduce the morbidity seen with the higher dose. It is well recognized that higher doses of cranial irradiation (21 to 24 Gy) can cause significant loss in standing height.4 -6 At lower doses, the effects on growth and, more importantly, on final height have been less clear. 68 Early and precocious puberty in girls have also been reported after both doses of cranial irradiation.Disproportion at final height after treatment for ALL in childhood was recently reported by our group. This suggests that at least in some children, much if not all of the height loss is due to a reduction in sitting height."' In this study, we examined the effect of both 18 Gy and 24 Gy of cranial irradiation on growth and the timing and duration of puberty. PATIENTS AND METHODSYoung adult survivors of childhood ALL were identified from three regional pediatric oncology/hematology centers. All had received combination chemotherapy and cranial irradiation as CNS prophylaxis. All were in first remission, and none had received either mean age at menarche occurred significantly earlier than in the normal population. In boys, there was a normal timing of PHV. The amplitude of PHV was significantly reduced in both sexes and in both dose groups. Parameters of pubertal duration (PHV to menarche, PHV to FH, and menarche to FH) were not significantly different from normal population values.Conclusion: In conclusion, puberty occurred early in girls, but not in boys. Amplitude of PHV was reduced in both sexes, with no reduction in the duration of puberty. It is likely that disturbances of both ti...

Modelling Height in Adolescence: A Comparison of Methods for Estimating the Age at Peak Height Velocity.

“…The age of peak height velocity (PHV) is often thought of as the gold standard of non-invasive measures of maturational status in observational studies. Age at PHV has been widely used as an outcome (Didcock et al, 1995;Mason et al, 2011;Nielsen, 1985;Price et al, 1988), exposure of interest (Gastin et al, 2013;Mao et al, 2013;Sherar et al, 2007), or as a covariate to control for confounding (Baxter-Jones et al, 2011;Darelid et al, 2012;Forwood et al, 2004). The appeal of age at PHV is twofold: (1) it applies equally to both boys and girls (Sherar et al, 2004); and (2) the measure appears to be objective, particularly in comparison to other methods that rely on subjective decisions about physical development of primary (Taranger et al, 1976) (orchoidometry) and secondary sex characteristics (Tanner, 1962) (Tanner Staging), recall of (semi-) specific biological events (age at menarche (Bergsten-Brucefors, 1976;Damon & Bajema, 1974;Damon et al, 1969)/voice breaking (Billewicz et al, 1981;Hagg & Taranger, 1980)), comparison of skeletal (Greulich & Pyle, 1959;Roche, 1988;Tanner et al, 1962Tanner et al, , 1975 and dental (Demirjian & Goldstein, 1976) radiographs with pre-defined standards or description or as a percentage of predicted adult stature (Bayley & Pinneau, 1952;Khamis & Roche, 1994;Roche et al, 1975;Tanner et al, 1975).…”

Raised blast glutathione levels are associated with an increased risk of relapse in childhood acute lymphocytic leukemia

“…A number of survivors suffer long-term side effects from their treatment, including intellectual impairment, disorders of growth, cardiac damage, and second malignancies. [4][5][6][7][8] A reduction in both the mortality rate and the toxic consequences of treatment remains a challenge for the improvement of ALL therapy in the future.…”

Puberty in Children with Cancer

“…In ALL girls, the timing of puberty is only moderately altered, with mean PHV at 10.7–11.0 years vs. 12.1 years in normals and mean timing of menarche at 12.2–12.3 years vs. 13.4 years, respectively [6]. Furthermore, the degree of GHD in ALL children is usually more subtle than in brain tumour children.…”

“…Paradoxically, lower doses of irradiation may be associated with early puberty. In children irradiated with a dose of 2,500–4,750 cGy for a brain tumour, both genders are affected [3]; however, after a dose of 1,800–2,400 cGy for acute lymphoblastic leukaemia (ALL) only girls enter puberty early [4, 5, 6]. Thus, the capacity of radiation-induced damage to the central nervous system to induce early puberty is dose- related and the dose threshold for this effect is gender-specific.…”

“…The duration of puberty is normal, although pubertal growth is adversely affected with a reduction in peak height velocity (PHV) in both genders, and significantly less growth after menarche in early developers previously treated for leukaemia compared with normal early developers. Puberty occurs early in girls, but at the normal time in boys [6]. …”