Long-term adverse effects on dentition in children with poor-risk neuroblastoma treated with high-dose chemotherapy and autologous stem cell transplantation with or without total body irradiation

Abstract

Summary:Chemo-and radiotherapy may have injurious effects on developing teeth. In this long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims were: (1) to assess both the type and extent of the side-effects of the anticancer treatment on tooth development; and (2) to develop an index for expressing total damage to the permanent dentition. We studied the dental development from panoramic radiographs (PRG) of 18 long-term survivors treated under the age of 6 years with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was either HD chemotherapy and fractionated total body irradiation (TBI) of 10-12 Gy (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect index (DeI) was developed to describe the damage to the permanent dentition. The DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances in dental development including short roots, arrested root development, microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root defects, in contrast to none in the non-TBI group. All children in the TBI group had 2-12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8 excluded due to young age) had two and four missing permanent teeth, respectively. Microdontia was found at equal frequency in both groups. The mean value of the DeI was 70.0 (range 28-117) in the TBI group, 15.2 (range 4-34) in the non-TBI group (P Ͻ 0.001, Mann-Whitney U test) and 1.8 (range 0-15) in healthy adolescents. Disturbances in dental development may compromise occlusal function in poor-risk NBL patients after ASCT, especially when TBI is included in the conditioning regimen. Long-term dental follow-up and rehabilitation is required.

Agenesis and microdontia of permanent teeth as late adverse effects after stem cell transplantation in young children

“…18 To our knowledge, the current series of SCT patients is the largest reported to date with an agenesis prevalence of 31%, which is lower than the prevalence reported previously. 12,13,18 The present results are not easy to compare with earlier studies due to variations in methodology, age of the patients, and treatment protocols. In the study by Näsman et al, 12 all patients who underwent SCT received TBI in a single fraction, whereas only 71% of patients in the current study received TBI that was fractionated in all but 1 patient.…”

“…The underlying diseases also have been different (e.g., poor-risk NBL patients versus patients with mainly hematologic malignancies). 12,13,18 The current study included several diagnoses (Table 1).…”

“…16 Microdontia, registered from panoramic radiographs is more frequent after pediatric anticancer therapy, 10 -13,15,17,18 ranging from 10% after conventional chemotherapy for hematologic malignancies 12 to 78% after SCT in patients with neuroblastoma. 18 In the current study, we examined 1) the prevalence of tooth agenesis and microdontia and 2) the number of missing and microdontic teeth in the permanent dentition of SCT recipients. We also analyzed the roles of TBI and age at SCT in dental adverse effects.…”

Agenesis of a large number of permanent teeth after treatment of neonatal leukemia

“…There have been few studies on SCT recipients. It was reported that the preparative regimens for SCT caused tooth agenesis at frequencies ranging from 31 to 80% [1,4,8]. HDC tends to cause more frequent and more severe dental abnormalities compared with conventional chemotherapy.…”

“…Morphogenesis and calcification of teeth form a sequence of events that begins in utero and continues for 14-15 years [6]. Therefore, HDC administered in childhood causes permanent dental disturbance, including tooth agenesis, microdontia, and disturbed root development [1,7,8]. The scale of tooth abnormalities runs from mild mineralization of the enamel to arrested root development, microdontia and aplasia of the permanent teeth, depending on the patient's age at cancer therapy and the kinds and doses of cytotoxic agents.…”