title: Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning.
abstract: OBJECTIVE
  This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT).
  
  
  METHODS
  The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period.
  
  
  RESULTS
  PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS.
  
  
  CONCLUSIONS
  A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.
authors: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. Electronic address: Mabugid@emory.edu.
authors: Mustafa
authors: M
authors: Abugideiri
authors: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Ronica H
authors: RH
authors: Nanda
authors: Emory University, Atlanta, Georgia.
authors: Charlotte
authors: C
authors: Butker
authors: Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Chao
authors: C
authors: Zhang
authors: Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors: Sungjin
authors: S
authors: Kim
authors: Aflac Cancer Center and Blood Disorders Center, Children's Healthcare of Atlanta, and Pediatric Hematology, Oncology, Bone Marrow Transplant, Emory University, Atlanta, Georgia.
authors: Kuang-Yueh
authors: KY
authors: Chiang
authors: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Elizabeth
authors: E
authors: Butker
authors: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Mohammad K
authors: MK
authors: Khan
authors: Aflac Cancer Center and Blood Disorders Center, Children's Healthcare of Atlanta, and Pediatric Hematology, Oncology, Bone Marrow Transplant, Emory University, Atlanta, Georgia.
authors: Ann E
authors: AE
authors: Haight
authors: Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Zhengjia
authors: Z
authors: Chen
authors: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors: Natia
authors: N
authors: Esiashvili
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D064591:Allografts; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007223:Infant; D008168:Lung / Q000528:radiation effects*; D008297:Male; D011014:Pneumonia / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D011879:Radiotherapy Dosage; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003561:Cytarabine; D005047:Etoposide; D003520:Cyclophosphamide