title: Effect of unintentional cyclophosphamide underdosing on diffuse large B-cell lymphoma response to chemotherapy: a retrospective review.
abstract: BACKGROUND
  Between March 2012 and March 2013, a miscommunication in labelling between the drug compounder supplier and cancer centre pharmacies resulted in accidental overdilution of cyclophosphamide and gemcitabine used by several cancer centres in Canada. At our centre, 177 hematology patients were affected, among whom the largest subset of patients was those with diffuse large B-cell lymphoma. In this study, we evaluated the effect of such underdosing on disease response.
  
  
  METHODS
  We conducted a retrospective cohort study involving all patients with diffuse large B-cell lymphoma who received at least 1 chemotherapy cycle containing diluted cyclophosphamide at our centre and compared them with a historical group of patients matched by stage and age. The primary outcome was event-free survival (a composite of disease progression or death). Secondary outcomes included complete remission and overall response rate. Groups were compared using unpaired Student t, χ2 or Fisher exact tests, as appropriate. Survival analysis was done using the Kaplan-Meier method.
  
  
  RESULTS
  Event-free survival was no different between groups (log-rank p = 0.99). At a median follow-up of 548 days, progression or death occurred in 21 of 77 patients in the case group (27.3%) and in 24 of 74 patients in the control group (32.4%) (p = 0.5). At the end of treatment, complete remission was achieved in 41 patients in the case group (53.2%) and 43 patients in the control group (57.3%) (p = 0.6), whereas overall response rate was 71.4% in the case group and 66.7% in the control group (p = 0.5).
  
  
  CONCLUSIONS
  Compared with a historical control group, we found no differences in event-free survival or response rates among patients with diffuse large B-cell lymphoma who received 1 or more doses of accidentally diluted cyclophosphamide-containing chemotherapy.
authors.affiliation: Department of Medicine (Al-Ahmadi, Lazo-Langner, Mangel, Liu, Minuk), Division of Hematology, University of Western Ontario, London, Ont.; Department of Oncology (Al-Ahmadi), King Abdulaziz Medical City, Jeddah, Saudi Arabia; Department of Epidemiology and Biostatistics (Lazo-Langner), University of Western Ontario, London, Ont.; Pharmacy Services (Dhalla), London Regional Cancer Program, London, Ont.
authors.forename: Majed
authors.initials: M
authors.lastname: Al-Ahmadi
authors.affiliation: Department of Medicine (Al-Ahmadi, Lazo-Langner, Mangel, Liu, Minuk), Division of Hematology, University of Western Ontario, London, Ont.; Department of Oncology (Al-Ahmadi), King Abdulaziz Medical City, Jeddah, Saudi Arabia; Department of Epidemiology and Biostatistics (Lazo-Langner), University of Western Ontario, London, Ont.; Pharmacy Services (Dhalla), London Regional Cancer Program, London, Ont.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lazo-Langner
authors.affiliation: Department of Medicine (Al-Ahmadi, Lazo-Langner, Mangel, Liu, Minuk), Division of Hematology, University of Western Ontario, London, Ont.; Department of Oncology (Al-Ahmadi), King Abdulaziz Medical City, Jeddah, Saudi Arabia; Department of Epidemiology and Biostatistics (Lazo-Langner), University of Western Ontario, London, Ont.; Pharmacy Services (Dhalla), London Regional Cancer Program, London, Ont.
authors.forename: Joy
authors.initials: J
authors.lastname: Mangel
authors.affiliation: Department of Medicine (Al-Ahmadi, Lazo-Langner, Mangel, Liu, Minuk), Division of Hematology, University of Western Ontario, London, Ont.; Department of Oncology (Al-Ahmadi), King Abdulaziz Medical City, Jeddah, Saudi Arabia; Department of Epidemiology and Biostatistics (Lazo-Langner), University of Western Ontario, London, Ont.; Pharmacy Services (Dhalla), London Regional Cancer Program, London, Ont.
authors.forename: Ally Dhalla
authors.initials: AD
authors.lastname: Phm
authors.affiliation: Department of Medicine (Al-Ahmadi, Lazo-Langner, Mangel, Liu, Minuk), Division of Hematology, University of Western Ontario, London, Ont.; Department of Oncology (Al-Ahmadi), King Abdulaziz Medical City, Jeddah, Saudi Arabia; Department of Epidemiology and Biostatistics (Lazo-Langner), University of Western Ontario, London, Ont.; Pharmacy Services (Dhalla), London Regional Cancer Program, London, Ont.
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Medicine (Al-Ahmadi, Lazo-Langner, Mangel, Liu, Minuk), Division of Hematology, University of Western Ontario, London, Ont.; Department of Oncology (Al-Ahmadi), King Abdulaziz Medical City, Jeddah, Saudi Arabia; Department of Epidemiology and Biostatistics (Lazo-Langner), University of Western Ontario, London, Ont.; Pharmacy Services (Dhalla), London Regional Cancer Program, London, Ont.
authors.forename: Leonard
authors.initials: L
authors.lastname: Minuk