title: Exploring the association of hemoglobin level and adverse events in children with cancer presenting with fever in neutropenia.
abstract: BACKGROUND
  In children and adolescents with fever in neutropenia (FN) during chemotherapy for cancer, hemoglobin ≥90 g/L at presentation with FN had been associated with adverse events (AE). This analysis explored three hypothetical pathophysiological mechanisms potentially explaining this counterintuitive finding, and further analyzed the statistical association between hemoglobin and AE.
  
  
  METHODS
  Two of 8 centers, reporting on 311 of 421 FN episodes in 138 of 215 patients participated in this retrospective analysis based on prospectively collected data from three databases (SPOG 2003 FN, transfusion and hematology laboratories). Associations with AE were analyzed using mixed logistic regression.
  
  
  RESULTS
  Hemoglobin was ≥90 g/L in 141 (45%) of 311 FN episodes, specifically in 59/103 (57%) episodes with AE, and in 82/208 (39%) without (OR, 2.3; 99%CI, 1.1-4.9; P = 0.004). In FN with AE, hemoglobin was bimodally distributed with a dip around 85 g/L. There were no significant interactions for center, age and sex. In multivariate mixed logistic regression, AE was significantly and independently associated with leukopenia (leukocytes <0.3 G/L; OR, 3.3; 99%CI, 1.1-99; P = 0.004), dehydration (hemoglobinPresentation/hemoglobin8-72 hours ≥1.10 in untransfused patients; OR, 3.5; 99%CI, 1.1-11.4; P = 0.006) and non-moderate anemia (difference from 85 g/L; 1.6 per 10 g/L; 1.0-2.6; P = 0.005), but not with recent transfusion of packed red blood cells (pRBC), very recent transfusion of pRBC or platelets, or with hemoglobin ≥90 g/L as such.
  
  
  CONCLUSIONS
  Non-moderate anemia and dehydration were significantly and relevantly associated with the risk of AE in children with cancer and FN. These results need validation in prospective cohorts before clinical implementation.
authors.affiliation: Department of Pediatrics, University of Bern, Bern, Switzerland.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Ammann
authors.affiliation: Division of Oncology, Department of Pediatrics, University of Zurich, Zurich, Switzerland.
authors.forename: Felix K
authors.initials: FK
authors.lastname: Niggli
authors.affiliation: Department of Pediatrics, University of Bern, Bern, Switzerland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Leibundgut
authors.affiliation: Department of Pediatrics, University of Bern, Bern, Switzerland; Division of Oncology, Medical Services of the Statutory Health Insurance Baden-Württemberg, Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Teuffel
authors.affiliation: Division of Oncology, Department of Pediatrics, University of Zurich, Zurich, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bodmer
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000209:etiology*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D009503:Neutropenia / Q000209:etiology*; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins