title: Neurologic complications after allogeneic hematopoietic stem cell transplantation in children: analysis of prognostic factors.
abstract: Neurologic complications are serious complications after hematopoietic stem cell transplantation (HSCT) and significantly contribute to morbidity and mortality. The purpose of this study was to investigate the clinical features and prognosis in pediatric patients who had neurologic complications after allogeneic HSCT. We retrospectively reviewed the medical records of children and adolescents (19 years old or younger) who underwent allogeneic HSCT at our institution from 2000 to 2012. A total of 383 patients underwent 430 allogeneic transplantations. Among them, 73 episodes of neurologic complications occurred in 70 patients. The cumulative incidence of neurologic complications at day 400 was 20.0%. Almost two thirds of the episodes (63.0%, 46 of 73) occurred within 100 days after transplantation. Calcineurin inhibitor-related neurotoxicity was observed as the most common cause of neurotoxicity (47.9%, 35 of 73) and was significantly associated with earlier onset neurologic complications, seizure, and tremor. It also showed a significant association with lower probability of headache, abnormality of cranial nerve, and neurologic sequelae. In a multivariate analysis, days to neutrophil engraftment after HSCT, extensive chronic graft-versus-host disease (GVHD) and the existence of neurologic sequelae were identified as risk factors for mortality in patients who had neurologic complications (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.02 to 1.15; P = .011; HR, 5.98; 95% CI, 1.71 to 20.90; P = .005; and HR, 4.37; 95% CI, 1.12 to 17.05; P = .034, respectively). However, there was no significant difference in the 5-year overall survival between the patients who had neurologic complications without sequelae and the patients who did not have any neurologic complications (57.3% versus 61.8%, P = .906). In conclusion, we found that the major significant risk factors for mortality in pediatric recipients with neurologic complications were the existence of neurologic sequelae and extensive chronic GVHD.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji-Man
authors.initials: JM
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yae-Jean
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ju Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jee Hun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mun Hyang
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: hema2170@skku.edu.
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
mesh_terms: D000293:Adolescent; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D006261:Headache / Q000209:etiology / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012640:Seizures / Q000209:etiology / Q000473:pathology*; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014202:Tremor / Q000209:etiology / Q000473:pathology*; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D019653:Myeloablative Agonists
keywords: Allogeneic hematopoietic stem cell transplantation; Calcineurin inhibitor; Neurologic complication; Prognostic factor; Sequelae