Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies.
Chemotherapy-induced neutropenia (CIN) may increase infection risk for cancer patients; however, there is limited understanding on the quantitative relationships between severity and duration of CIN and infection risk.



This study combined individual data from adult cancer patients receiving no granulocyte colony-stimulating factor during the first chemotherapy cycle in six trials. We used area over the curve (AOC) of absolute neutrophil count (ANC) time-response curve (below different thresholds) to measure the combined effect of severity and duration of CIN. Time-dependent Cox proportional hazards models quantified the hazard of first infection associated with duration of grade 4 or grade 3/4 CIN and the hazard associated with AOC.



We analyzed data from 271 patients who had small cell lung cancer, non-Hodgkin's lymphoma, head and neck cancer, or breast cancer; 63.8 % of the patients had advanced cancer, and 77.5 % received chemotherapy regimens with high risk of febrile neutropenia. In the first cycle, 18.8 % of the patients had infection-related hospitalizations. Each additional day patients had grade 3/4 or grade 4 CIN was associated with 28 % (95 % CI 7, 51 %) and 30 % (95 % CI 10, 54 %) increased risk of infection-related hospitalization, respectively. Each unit increase in AOC (day × 10(9)/L ANC), with threshold of ANC < 0.5 × 10(9)/L, was associated with a significantly increased risk of infection-related hospitalization (hazard ratio 1.98; 95 % CI 1.35, 2.90).



Infection risk increases dramatically with each additional day of grade 3 or 4 CIN. Interventions limiting CIN severity and duration are of critical importance to reduce infection risk in cancer patients receiving chemotherapy.
Center for Observational Research, Amgen Inc., 1150 Veterans Blvd, South San Francisco, CA, 94080, USA. yanli.li@amgen.com.
Yanli
Y
Li
Hematology/Oncology, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Zandra
Z
Klippel
SimulStat Incorporated, 4370 La Jolla Village Dr, San Diego, CA, 92122, USA.
Xiaolong
X
Shih
Global Biostatistical Science, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Maureen
M
Reiner
TechData Service Company, LLC, 700 American Avenue, King of Prussia, PA, 19406, USA.
Hong
H
Wang
Center for Observational Research, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
John H
JH
Page
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007239:Infections / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000139:chemically induced*; D012306:Risk
Area over the curve; Chemotherapy-induced neutropenia; Infection; Infection-related hospitalization