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Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies

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Abstract

Purpose

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.

Methods

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.

Results

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 × 109/L ANC), with threshold of ANC < 0.5 × 109/L, was associated with a significantly increased risk of infection-related hospitalization (hazard ratio 1.98; 95 % CI 1.35, 2.90).

Conclusions

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.

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Acknowledgments

The authors would like to thank Martha Mutomba (on behalf of Amgen Inc.) for providing writing assistance.

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Authors and Affiliations

  1. Center for Observational Research, Amgen Inc., 1150 Veterans Blvd, South San Francisco, CA, 94080, USA

    Yanli Li

  2. Hematology/Oncology, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA

    Zandra Klippel

  3. SimulStat Incorporated, 4370 La Jolla Village Dr, San Diego, CA, 92122, USA

    Xiaolong Shih

  4. Global Biostatistical Science, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA

    Maureen Reiner

  5. TechData Service Company, LLC, 700 American Avenue, King of Prussia, PA, 19406, USA

    Hong Wang

  6. Center for Observational Research, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA

    John H. Page

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  1. Yanli Li
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Corresponding author

Correspondence to Yanli Li.

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Funding

This study was supported by Amgen Inc.

Conflict of interest

Yanli Li, Zandra Klippel, Maureen Reiner, and John H. Page are employees of and own stock in Amgen Inc. Xiaolong Shih and Hong Wang are consultants and are funded by Amgen Inc.

Research involving human participants and/or animals

Informed consent was obtained from all individual participants included in the original studies. For this type of study, formal consent is not required.

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Li, Y., Klippel, Z., Shih, X. et al. Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies. Support Care Cancer 24, 4377–4383 (2016). https://doi.org/10.1007/s00520-016-3277-0

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  • DOI: https://doi.org/10.1007/s00520-016-3277-0

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