Factors Influencing Pulmonary Toxicity in the Setting of Total Body Irradiation-Based Myeloablative Conditioning in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Аннотация:To evaluate factors associated with increased risk of pulmonary toxicity in pediatric patients after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic hematopoietic stem cell transplantation (HSCT). The records of 129 consecutive pediatric patients (range, 1-21 years) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI dose ranged from 10.5 to 14Gy, lung doses were reduced to 10Gy with partial transmission blocks. The TBI dose rate ranged from 5.57cGy/min to 20.85cGy/min. Pulmonary toxicity developed in 70.5% of patients, which proved to be fatal in 38.5% of those patients. Patients with any type of infection at any point during the follow-up period were more likely to develop pulmonary toxicity (p=0.009), and patients with bacterial infection during the follow-up period had the highest incidence of pulmonary toxicity (p=0.038). The presence of any grade of acute graft-versus-host-disease (GVHD) was associated with an increased incidence of pulmonary toxicity (p=0.034), which developed in 94.4% of patients with grade III-IV GVHD (p=0.001). TBI dose rate was significantly related to the development of pulmonary toxicity (p=0.0495). Pulmonary toxicity was 3.51 times more likely to develop in patients receiving a TBI dose rate greater than 15cGy/min (p=0.017). Overall survival was significantly shorter in patients who developed pulmonary toxicity (p=0.0053). A high incidence of pulmonary toxicity was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. The presence of high grade acute GVHD and infection were the most significant factors contributing to the development of pulmonary toxicity. TBI dose rate should be aimed to be kept below 15cGy/min to decrease the risk of pulmonary injury.
