Evaluation of early discharge after hospital treatment of neutropenic fever in acute myeloid leukemia (AML)

Background: Hospital admission for neutropenic fever in patients with AML is a standard practice. However, discharge practices vary once patients become afebrile, with many patients hospitalized until rise in the absolute neutrophil count (ANC) to >500 (ANC recovery). Data to support this practice are sparse. We hypothesized that patients admitted for neutropenic fever, particularly if in complete remission (CR) or about to enter CR following the chemotherapy course associated with neutropenic fever, might be safely discharged earlier (ED). Benefits of ED are less exposure to hospital pathogens, reduced cost, increased availability of beds for patients more in need of urgent care, and potentially, enhanced psychological well-being.

Methods: We identified patients age 18-70 with newly diagnosed AML who were admitted to the University of Washington Medical Center with neutropenic fever between January 2008 and May 2010. We compared subsequent (within 30 days of discharge) deaths, intensive care unit (ICU) admissions, and readmissions for neutropenic fever according to discharge ANC, regarded as a numerical variable using the Mann-Whitney U test and as <500 vs >500 using the Fisher Exact test. We used the Mann-Whitney U or Spearman correlation to analyze the relation between ANC at discharge and other covariates that might have affected outcome: age, ECOG performance status at admission for neutropenic fever, days inpatient, remission status, and type of infection (pneumonia, gram negative bacteremia, others).

Results: We evaluated 49 patients discharged after admission for neutropenic fever, 26 of whom were discharged with an ANC <500. Thirty five of the patients were in CR or entered CR following the chemotherapy course associated with their neutropenic fever admission. Patients who were discharged with lower ANC were more likely to be readmitted with neutropenic fever (Mann-Whitney U p=0.03), although this was not true using ANC categorized as < vs >500 (Fisher Exact p=0.24, 95% confidence interval -0.47, 0.11). There was no relation between ANC at discharge and subsequent admission to an ICU (Mann-Whitney U p=0.50, Fisher Exact p=0.64, 95% confidence interval 0.2, 0.34 using the 500 ANC cut off). One patient died: a 55 year old discharged with ANC 0 after successful treatment of neutropenic fever died 19 days after hospital readmission with fever of unknown origin. Stenotrophomonas maltophilia pneumonia and sepsis were discovered 14 days after readmission. Assuming a beta distribution and rates of death of 1/26 for discharge with ANC<500 and 0/23 for discharge with ANC>500, the probability that a discharge ANC with <500 is associated with a higher death rate is 0.019. The number of events was too small for a multivariate analysis. However, patients with better performance status (<ECOG 2) or who spent a shorter time in hospital after admission for neutropenic fever were more likely to be discharged with lower ANC (Fisher exact p=0.09 and Spearman p=0.02 respectively), while the likelihood of discharge with ANC<500 was unrelated to age, remission status, or type of infection. Thus we examined the relation between ANC and readmission for neutropenic fever separately in patients with better or worse performance status and in patients who spent more or less than the median time (8 days) in hospital after admission for neutropenic fever. This analysis indicated that patients discharged with lower ANC were more likely to be readmitted only if they had spent more than 8 days in hospital or if they were performance status <2.

Conclusions: Our results suggest that an ANC of 500 is an excessively high cut off for discharge following hospitalization for neutropenic fever. The rate of rise of the ANC, as well as its absolute value, may also play a role.