Background: Hematologic toxicities are common side effects of cancer chemotherapy. Despite advances in supportive care, febrile neutropenia (FN) continues to represent a serious adverse event often requiring hospitalization and is associated with an increased risk of mortality. The purpose of this analysis was to investigate the impact of comorbidities and infectious complications on in-patient length of stay (LOS) and mortality in hospitalized patients with cancer and neutropenia over the past decade.
Methods: Hospitalization data from the University Health Consortium database inclusive of the years 2004-2012 from 239 US medical centers were analyzed. Cancer type, presence of neutropenia, comorbidities, and infection type were based on ICD-9-CM codes recorded during hospitalization. This analysis includes adult patients with malignant disease and neutropenia. Patients undergoing bone marrow or stem cell transplantation were excluded. For patients with multiple hospitalizations, the first admission during the time period studied was utilized. Primary study outcomes included hospital length of stay (LOS≥10 days) and in-hospital mortality. Multivariate logistic regression analysis was utilized to study the impact of major comorbidities on the primary outcomes. Major comorbidities under consideration included heart, liver, lung, renal, cerebrovascular, peripheral-vascular disease, diabetes and venous thromboembolism.
Results: Among 135,309 patients with cancer hospitalized with neutropenic events, one-third were age 65 years or older and 51% were male. Approximately one-quarter (24.5%) of patients experienced more than one admission with FN. The mean (median) length of stay increased progressively from 11.1 (6) days in 2004 to 12.8 (7) days in 2012. Patients with leukemia, lymphoma and central nervous system (CNS) malignancies experienced the longest mean LOS (21.4, 10.5, 10.2 days, respectively). Overall, 50,846 (37.6%) had a LOS≥10 days and 10,261 (7.6%) patients died during the hospitalization with no difference seen over the time period of observation. (P=.30). Greater rates of mortality were observed in patients with lung (11.2%) or CNS (9.3%) malignancies, and leukemia (9.3%). Infectious complications were documented in 59.5% of patients and their presence was associated with greater LOS≥10 days (48.2% vs. 22.0%) and higher mortality (11.2% vs. 2.3%). Greater LOS≥10 days (51.6% vs. 37.1%) and increased mortality (9.8% vs. 7.5%) were also observed among obese patients with cancer. Likewise, patients with multiple comorbid conditions had more prolonged hospitalizations and a greater risk of in-hospital mortality. (Table)
| . | Solid tumors . | Lymphoma . | Leukemia . | ||||||
|---|---|---|---|---|---|---|---|---|---|
| No. of comorbidities | No. of patients | % died | % with LOS≥10 days | No. of patients | % died | % with LOS≥10 days | No. of patients | % died | % with LOS≥10 days |
| 0 | 17,858 | 0.9 | 11.2 | 8,189 | 0.6 | 17.0 | 10,395 | 0.8 | 53.5 |
| 1 | 18,172 | 3.4 | 17.9 | 7,751 | 2.6 | 26.6 | 11,380 | 3.4 | 63.2 |
| 2 | 14,250 | 8.9 | 27.2 | 5,386 | 8.1 | 41.0 | 8,603 | 9.7 | 69.9 |
| 3 | 7,499 | 18.0 | 38.4 | 2,861 | 18.4 | 55.2 | 5,040 | 22.8 | 77.7 |
| 4 | 2,705 | 25.1 | 51.4 | 1,060 | 33.6 | 70.5 | 2,004 | 38.1 | 83.1 |
| ≥ 5 | 602 | 35.2 | 62.3 | 278 | 39.9 | 80.6 | 577 | 49.0 | 87.0 |
| All patients* | 61,086 | 7.0 | 22.6 | 25,525 | 6.6 | 32.2 | 37,999 | 9.2 | 65.4 |
| . | Solid tumors . | Lymphoma . | Leukemia . | ||||||
|---|---|---|---|---|---|---|---|---|---|
| No. of comorbidities | No. of patients | % died | % with LOS≥10 days | No. of patients | % died | % with LOS≥10 days | No. of patients | % died | % with LOS≥10 days |
| 0 | 17,858 | 0.9 | 11.2 | 8,189 | 0.6 | 17.0 | 10,395 | 0.8 | 53.5 |
| 1 | 18,172 | 3.4 | 17.9 | 7,751 | 2.6 | 26.6 | 11,380 | 3.4 | 63.2 |
| 2 | 14,250 | 8.9 | 27.2 | 5,386 | 8.1 | 41.0 | 8,603 | 9.7 | 69.9 |
| 3 | 7,499 | 18.0 | 38.4 | 2,861 | 18.4 | 55.2 | 5,040 | 22.8 | 77.7 |
| 4 | 2,705 | 25.1 | 51.4 | 1,060 | 33.6 | 70.5 | 2,004 | 38.1 | 83.1 |
| ≥ 5 | 602 | 35.2 | 62.3 | 278 | 39.9 | 80.6 | 577 | 49.0 | 87.0 |
| All patients* | 61,086 | 7.0 | 22.6 | 25,525 | 6.6 | 32.2 | 37,999 | 9.2 | 65.4 |
LOS – length of stay; * 10,699 patients with other type or multiple tumors not included in the table
The trend toward longer LOS and greater mortality with increased number of comorbidities persisted in multivariate analyses after adjusting for cancer type, age, gender, ethnicity and type of infection (odds ratio (OR) per +1 comorbidity increase: [mortality: OR =1.89; 95% CI: 1.85-1.92; P<.0001], [LOS: OR=1.56; 95% CI: 1.54-1.58; P<.0001]).
Conclusions: Major medical comorbidities are common among hospitalized patients with cancer and neutropenia. Importantly, such comorbidities are associated with prolonged hospitalization and increased risk of in-hospital mortality with significantly worse outcomes in patients with lymphoma or leukemia. Greater awareness of risk factors associated with poor prognosis in cancer patients hospitalized with neutropenic complications as well as validated risk tools to better identify low risk as well high risk patients may guide more personalized cancer care, potentially improving clinical outcomes and lowering the cost of care.
Crawford:Amgen: Consultancy. Dale:Amgen: Consultancy, Honoraria, Research Funding. Lyman:Amgen: Research Funding.
Author notes
Asterisk with author names denotes non-ASH members.
