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 wi th the Lyon-Marseille-Curie-East of France Group protocol, consisting of high-dose chemotherapy schedules in combination with total body irradiation (TBI) an d autologous bone marrow transplantation (ABMT), to determine the extent an d timing of any changes seen and to describe lace clinical and functional p ulmonary sequelae. Procedures. Eighteen children (1.5-6.9 years of age at T BI) performed pulmonary function tests (PFTs). These included measurement o f functional residual capacity (FRC) to assess lung growth and dynamic lung compliance (C-Ldyn) and lung transfer factor for CO (T-LCO) for evaluation of distal bronchi and/or interstitial abnormalities. Results. The clinical follow-up showed that bronchopulmonary symptoms occurred in 12 children. T hree 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 T-LCO 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 T-LCO, suggesting restrictive ventilatory defects rather th an pulmonary fibrosis. Individual analysis showed PFT defects in 100% of ch ildren 4 years after TBI. There was a higher incidence of lung pathology af ter 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. PF T defects were found in all children 4 years after TBI-ABMT, but they remai ned within acceptable limits except in very young children. (C) Wiley-Liss, Inc.