title: Late-onset Pneumocystis jirovecii pneumonia post-fludarabine, cyclophosphamide and rituximab: implications for prophylaxis.
abstract: OBJECTIVE
  Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post-FCR in the era of highly sensitive molecular diagnostics and (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computerised tomography (CT).
  
  
  METHODS
  All patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory-confirmed PJP cases during this time were identified from an electronic database.
  
  
  RESULTS
  Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, (18) F-FDG PET demonstrated bilateral ground-glass infiltrates. Median CD4(+) lymphocyte counts at time of PJP diagnosis and 9-12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4-24 months).
  
  
  CONCLUSIONS
  Given the high rate of late-onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post-FCR, particularly in pretreated patients. Further evaluation of the role of CD4(+) monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis.
authors.affiliation: Department of Infectious Diseases and Infection Control, Peter MacCallum Cancer Centre, East Melbourne, Vic, Australia. haeusler@petermac.org
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Haeusler
authors.forename: Monica A
authors.initials: MA
authors.lastname: Slavin
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Senthil
authors.initials: S
authors.lastname: Lingaratnam
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Teh
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Karin A
authors.initials: KA
authors.lastname: Thursky
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Worth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000150:complications / Q000188:drug therapy; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D000069283:Rituximab; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Pneumocystis jirovecii pneumonia; cancer; fludarabine, cyclophosphamide and rituximab; guideline; lymphocyte; prophylaxis