Longitudinal clinical and functional pulmonary follow-up after megatherapy, fractionated total body irradiation, and autologous bone marrow transplantation for metastatic neuroblastoma.

Background: A prospective follow-up was undertaken to document longitudinal changes in lung function in children with neuroblastoma treated with the Lyon-Marseille-Curie-East of France Group protocol, consisting of high-dose chemotherapy schedules in combination with total body irradiation (TBI) and autologous bone marrow transplantation (ABMT), to determine the extent and timing of any changes seen and to describe late clinical and functional pulmonary sequelae.
Procedures: Eighteen children (1.5-6.9 years of age at TBI) performed pulmonary function tests (PFTs). These included measurement of functional residual capacity (FRC) to assess lung growth and dynamic lung compliance (CLdyn) and lung transfer factor for CO (TLCO) for evaluation of distal bronchi and/or interstitial abnormalities.
Results: The clinical follow-up showed that bronchopulmonary symptoms occurred in 12 children. Three of them were clinically severely incapacitated. Serial PFTs showed an initial decrease of all mean values 6 months after TBI, with improvement in mean values of FRC and TLCO at 1 year. Thereafter, a significant decrease of mean FRC and CLdyn was observed from 2 years to 4 years after TBI with preservation of TLCO, suggesting restrictive ventilatory defects rather than pulmonary fibrosis. Individual analysis showed PFT defects in 100% of children 4 years after TBI. There was a higher incidence of lung pathology after two blocks of high-dose chemotherapy than after one block (100% versus 40%) and more severe sequelae. However these children had residual disease present after induction associated with lower baseline PFT.
Conclusions: PFT defects were found in all children 4 years after TBI-ABMT, but they remained within acceptable limits except in very young children.