| Abstract |
The impact of contemporary treatment for children with Hodgkin's disease upon the pattern of growth, final height and gonadal function was evaluated on patients treated according to the MDP protocol with either chemotherapy (CT, consisting of six cycles of doxorubicin, procarbazine, prednisone, vincristine and cyclophosphamide), radiation (RT), or both (CT+RT). For analyzing growth and final height, the study population included 80 patients (54 males), age less than 14 years at diagnosis, with histologically confirmed Hodgkin's disease. Median age at diagnosis was 9.7 years (range, 2.4 to 14.0 years). Patients received RT (n=11), CT (n=23) or CT+RT (n=46). Heights were obtained at diagnosis, at the end of treatment, one, two and three years following the end of treatment and at attainment of final height. Heights were converted to age and sex adjusted standard deviation scores (SDS). Gonadal function was evaluated in 65 patients (36 males) with Hodgkin's disease in complete remission after treatment with RT (n=13), CT (n=9) or CT+RT (n=43). Median age at diagnosis was 13.1 years (range, 2.4 to 22.6) and median age at evaluation was 22.6 years (range, 15.1 to 33.7) which was 6.7 years (range, 2.0 to 19.8) after the completion of all treatments. For the purpose of gonadal outcome analysis, patients were divided into three groups: Group A: patients who received only RT that did not include the pelvis (8 females, 5 males); Group B : patients who received CT but no pelvic RT (15 females, 25 males); Group C: patients who received CT plus pelvic RT (6 females, 6 males). There was a significant change in height SDS at the end of treatment compared with the height SDS at diagnosis for all three groups (CT: -0.24, p=0.012; RT: +0.09, p=0.027; CT+RT: -0.33, p<0.001). Beyond the three years following treatment, the rate of change of height SDS was not statistically different between the three treatment groups. Final height SDS was found to be decreased for patients receiving RT+CT (-0.41 SDS, p=0.02; n=31). The change in final height SDS for patients receiving RT or CT only was -0.36 (p=0.28; n=14) and +0.42 (n=4), respectively. Loss of final height SDS correlated with younger age at diagnosis (p=0.005). Patients receiving higher RT doses tended to fair worse (p=0.08). The height SDS observed at the end of treatment correlated with the final adult height SDS (r=0.35, p<0.001). All patients in the gonadal cohort progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25 and 5/6 and testicular volume was decreased in 1/3, 4/11 and 2/3 Group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 89% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone. FSH and LH were increased in 0/8, 3/15 and 2/6 Group A, B and C female patients, respectively, at last follow up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. A total of six females delivered eight normal children. In summary, pediatric patients treated for Hodgkin's disease with the combination of RT and CT suffer a small but significant decrease in their final height SDS. Younger patients and those treated with higher RT doses appear to experience the greatest loss of their height potential. Additionally, the majority of male patients who received CT ±RT show evidence of germ cell dysfunction, while Leydig cell function is unaffected in most of them. In females, although abnormal function early following the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential and those tests should be repeated and followed accordingly.
|
Collections
