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

AbstractBackgroundHospital 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.MethodsWe 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).ResultsWe 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.ConclusionsOur 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

Comparison of Acute Myeloid Leukemia Measurable Residual Disease Detection By Flow Cytometry in Peripheral Blood and Bone Marrow

BACKGROUND: The current recommendation against the need for bone marrow aspiration (BMA) in routine follow-of persons with acute myeloid leukemia (AML) in remission preceded the recognition that multiparameter flow cytometry (MFC) is a sensitive and specific means to detect imminent morphologic relapse. Given this recognition, we wondered whether BMA is now necessary, or if concordance between MFC results in peripheral blood (PB) and BMA is such as to make BMA unnecessary, at least for evaluation of measurable residual disease (MRD) by MFC. Previous studies have demonstrated a strong correlation between disease detection by MFC in PB and BMA. Here we examined 724 paired PB and BMA samples from 482 patients to further examine the concordance between PB and BMA blast detection by MFC, particularly among patients in morphologic remission. PATIENTS AND METHODS: We included adults in our institutional AML database, covering 2008-2018. Our Hematopathology database was queried to identify PB and BMA MFC sample pairs with samples considered "paired" if measured within one week of each other. If an individual had multiple pairs, all were included unless otherwise specified. Ten-color MFC was performed routinely on BMA aspirates with a panel of three antibody combinations, with the same antibody combinations applied to PB samples. When identified, the abnormal population was quantified as a percentage of the total CD45+ white cell events. Any level of residual disease was considered positive. Complete remission (CR) and relapse were defined according to the European LeukemiaNet 2017 classification. Relationship between PB and BMA blast % was measured using Spearman's Rank-Order Correlation. Relationship between PB and BMA samples identified as positive or negative is illustrated using 2 X 2 tables (Table 1). RESULTS: Considering all 724 sample pairs, the Spearman correlation coefficient between PB and BMA blast percentage was 0.93, and was 0.91 considering only the first sample pair for each individual patient (n= 482). 315 sample pairs were positive by PB, 97% of which were also positive by BMA while 95% of 409 pairs negative by PB were also negative by BMA. Similar results were seen considering only a patient's first pair. Restricting analysis to patients with pairs obtained between the dates of CR and relapse, the Spearman correlation coefficient was 0.82 with 91% of 35 cases positive in PB also positive in BMA; 93% of 114 pairs negative in PB were also negative in marrow. As a complementary means to compare pairs when AML burden was low, we examined only pairs where the BMA MFC showed <5% blasts. Here, the Spearman correlation coefficient between PB and BMA blasts was 0.83. 90% of 70 positive PB cases were also positive by BMA while 95% of 295 negative PB cases were also negative by BMA. Examining pairs taken from patients in morphologic remission immediately prior to undergoing hematopoietic cell transplant yielded a Spearman correlation coefficient of 0.92, with all 9 PB positive cases also being positive in BMA and 96% of PB negative cases being negative in BMA. CONCLUSIONS: This is the largest cohort of AML PB and BMA sample pairs analyzed by MFC to-date. The percentages of blasts measured in PB and BMA are strongly correlated. In the 365 pairs from patients with MRD-level disease, the predictive value of PB MFC positivity for BMA positivity was 90% (63/70) while the predictive value PB MFC negativity for BMA negativity was 95%. Disclosures Othus: Glycomimetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Gardner:Abbvie: Speakers Bureau. Walter:BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding; Argenx BVBA: Consultancy; Aptevo Therapeutics: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Astellas: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership

Outpatient management following intensive induction chemotherapy for myelodysplastic syndromes and acute myeloid leukemia: a pilot study

Due to infectious and bleeding risks, adults with acute myeloid leukemia or high-risk myelodysplastic syndromes typically remain hospitalized after remission induction chemotherapy until blood count recovery. Here, we explored the medical and financial effects of discharge immediately after chemotherapy completion with close outpatient follow up. Within 12 months, 15 patients fulfilling both medical and logistical criteria were discharged early, whereas 5 patients meeting medical criteria only served as inpatient controls. No patient died. Patients discharged early spent a median of 8 days (range 3–36 days), or 54% of their study time, as outpatients. These patients required less time on intravenous antibiotics (6 vs. 16 days; P=0.11), received fewer red blood cell transfusions (0.25 vs. 0.48 units/day; P=0.08), and incurred lower median daily charges ($3,270 vs.$5,467; P=0.01) than controls. Thus, early discharge of selected patients appears, safe and may reduce cost and resource utilization