title: Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis.
abstract: OBJECTIVE
  Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue.
  
  
  METHODS
  We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013.
  
  
  RESULTS
  Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%.
  
  
  CONCLUSIONS
  NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Silvia
authors: S
authors: Park
authors: Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Cheol-In
authors: CI
authors: Kang
authors: Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Doo Ryeon
authors: DR
authors: Chung
authors: Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Kyong Ran
authors: KR
authors: Peck
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Won Seog
authors: WS
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Seok Jin
authors: SJ
authors: Kim
keywords: Fever; Lymphoma; Rituximab
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