Growth in children with poor-risk neuroblastoma after regimens with or without total body irradiation in preparation for autologous bone marrow transplantation

Abstract

Summary:Impaired growth after TBI prior to BMT has been a constant finding in children with leukemia. The growth of poor-risk neuroblastoma (NBL) survivors treated with myeloablative preparative regimens and ABMT at the Hospital for Children and Adolescents, University of Helsinki, since 1982 is reported. Two separate groups were analyzed: (1) The TBI − patients (n = 15) were conditioned with high-dose chemotherapy only. They had been treated at the age of 1.0-6.3 (mean 3.0) years and the post-ABMT follow-up time was 1.5-14.5 (mean 7.7) years. (2) The TBI + patients (n = 16) had received TBI in addition to high-dose chemotherapy. They had been treated at the age of 1.3-4.8 (mean 3.0) years, and the post-ABMT follow-up time was 1.5-8.0 (mean 4.7) years. The height standard deviation score (SDS) was similar for the two groups at the time of diagnosis, −0.3 ± 1.2 (mean ± s.d.), and at the time of ABMT, −0.7 ± 1.1. After transplantation, the height SDS continued to decrease in the TBI + group, the mean being −2.0 SDS at 5 years after ABMT. In the TBI − group, the mean height SDS remained within −0.7 to −0.9 to the 10 years of follow-up. Five patients received growth hormone (GH) therapy starting 2-6 years after ABMT. They all had low GH secretion in provocative tests. All showed some response to GH therapy. The mean height SDS increased 0.4 SDS during the 3 years following the start of GH therapy, while in the untreated patients a decrease of 0.8 SDS during the corresponding time (P = 0.009) was observed. We conclude that NBL patients grow poorly following ABMT when TBI is included in the conditioning regimen, but close to normally when treated without TBI. The need for GH therapy should be evaluated early to avoid an unnecessary decrease in final height.

Late effects in children treated with intensive multimodal therapy for high-risk neuroblastoma: High incidence of endocrine and growth problems

“…Patients who did not receive TBI were significantly taller than those who had received TBI, similar to the findings of Hovi et al 11 TBI is the one treatment modality that might place these patients at risk for GH insufficiency. However, they did not test as GH deficient on stimulation testing or appear to have GH neurosecretory dysfunction; and while short-term response to GH treatment was good, long-term outcome was not.…”

Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation

“…[21][22][23] We documented GH deficiency in only one of nine survivors tested, indicating that factors other than growth hormone insufficiency, such as radiotherapy fields encompassing vertebral bodies and endocrinopathies involving thyroid 33 and sex hormone secretion, contribute to growth failure in these patients. Pubertal failure has been a significant problem among our cohort and has been noted in NB survivors 24 and recipients of fractioned TBI for transplant conditioning.…”

“…6,10 Late regimen-related toxicities have increasingly been recognized and include second malignancy, 17 hearing loss [18][19][20] and multiple endocrinopathies. [21][22][23][24] Despite this, neuropsychological and adaptive functioning appear to be well preserved. 25,26 Since 1985, high-risk NB patients at our hospital have been transplanted with an unpurged autologous graft.…”

High‐dose chemotherapy followed by locoregional irradiation improves the outcome of patients with international neuroblastoma staging system Stage II and III neuroblastoma with MYCN amplification

“…Among the different drug combinations used in the HDC setting, the combination of busulfan and melphalan has been associated with better disease control 11 and was preferred to total body irradiation conditioning, which has severe side effects on growth. 34 However, the use of high doses of busulfan may compromise further fertility in females. 35 A longer follow-up will be necessary to determine the long-term side effects of such conditioning and of locoregional RT.…”