Predictors for chemotherapy-related severe or febrile neutropenia: a review of the clinical literature

Abstract

Purpose. This paper summarizes a literature review of the risk factors and predictors for chemo-therapy-related severe or febrile neutropenia (grades 3 and 4). It explores the extent to which the literature supports the current ASCO guidelines, and assesses the feasibility of developing a predictive algorithm for patients who would benefit from rHuG-CSF (Neupogen). Methods. An electronic literature search for English articles and abstracts identified 718 abstracts for review. From these, 121 articles were reviewed in depth. The review captured risk factors and predictors for grade 3-4 and/or febrile neutropenia, study design, patient characteristics, chemotherapy treatment, and the incidence of grade 3-4 and/or febrile neutropenia. Results. Twenty-eight potential risk factors and predictors for severe or febrile neutropenia among cancer patients were identified and could be classified as patient-related, treatment-related, or disease-related characteristics. Some results were inconsistent across studies due to a lack of standardized methods of assessment and reporting. Approximately 1/3 of the factors were mentioned in more than one study and provided information on the statistical significance of findings. Several factors had cross-study support of their value and confirmed previous findings. Strong predictors of severe/febrile neutropenia included advanced age, performance status, myelosuppressive chemotherapy regimen, early low blood counts, the depth of the absolute neutrophil count (ANC) nadir, and a precipitous, early drop in blood counts of all hematopoietic cell types. Conclusions. This literature review identified several key predictors and risk factors for development of grades 3 and 4 neutropenia in cancer patients. While additional confirmation is needed, there is sufficient consistency in the literature to support use of risk factors to identify patients who may need supportive care. Some of these risk factors were included in the ASCO CSF guidelines for the use of prophylactic support such as G-CSF; however, the ASCO publications have not included other important risk factors, such as age and early reduced ANC levels.