Chow Victor, Dorcy Kathleen Shannon, Sandhu Ravinder, Gardner Kelda, Becker Pamela, Pagel John, Hendrie Paul, Abkowitz Janis, Appelbaum Frederick, Estey Elihu
University of Washington School of Medicine, Seattle, USA ; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, USA.
Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, USA.
Leuk Res Rep. 2013 Mar 19;2(1):26-8. doi: 10.1016/j.lrr.2013.01.001. eCollection 2013.
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.
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).
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.
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.
急性髓系白血病（AML）患者因中性粒细胞减少性发热住院是一种标准做法。然而，一旦患者退热，出院做法各不相同，许多患者会住院直至绝对中性粒细胞计数（ANC）升至>500（ANC恢复）。支持这种做法的数据很少。我们假设，因中性粒细胞减少性发热入院的患者，特别是处于完全缓解（CR）状态或在与中性粒细胞减少性发热相关的化疗疗程后即将进入CR的患者，可能可以更早安全出院（ED）。早期出院的好处包括减少接触医院病原体、降低成本、为更需要紧急护理的患者增加床位可用性，以及潜在地增强心理健康。
我们确定了2008年1月至2010年5月期间因中性粒细胞减少性发热入住华盛顿大学医学中心的18 - 70岁新诊断AML患者。我们根据出院时的ANC比较了随后（出院后30天内）的死亡、重症监护病房（ICU）入院以及中性粒细胞减少性发热再入院情况，将ANC视为数值变量使用Mann - Whitney U检验，将其分为<500与>500使用Fisher精确检验。我们使用Mann - Whitney U或Spearman相关性分析出院时的ANC与其他可能影响结局的协变量之间的关系：年龄、中性粒细胞减少性发热入院时的东部肿瘤协作组（ECOG）体能状态、住院天数、缓解状态以及感染类型（肺炎、革兰阴性菌血症、其他）。
我们评估了49例因中性粒细胞减少性发热入院后出院的患者，其中26例出院时ANC<500。35例患者处于CR状态或在与中性粒细胞减少性发热入院相关的化疗疗程后进入CR。出院时ANC较低的患者更有可能因中性粒细胞减少性发热再次入院（Mann - Whitney U p = 0.03），尽管将ANC分类为<500与>500时并非如此（Fisher精确检验p = 0.24，95%置信区间 - 0.47，0.11）。出院时的ANC与随后入住ICU之间没有关系（Mann - Whitney U p = 0.50，Fisher精确检验p = 0.64，使用500的ANC临界值时为95%置信区间0.2，0.34）。1例患者死亡：1例55岁患者在成功治疗中性粒细胞减少性发热后出院时ANC为0，在因不明原因发热再次入院19天后死亡。再次入院14天后发现嗜麦芽窄食单胞菌肺炎和败血症。假设为β分布，ANC<500出院时的死亡率为1/26，ANC>500出院时的死亡率为0/23，出院时ANC<500与较高死亡率相关的概率为0.019。事件数量太少，无法进行多变量分析。然而，体能状态较好（<ECOG 2）或中性粒细胞减少性发热入院后住院时间较短的患者更有可能以较低的ANC出院（分别为Fisher精确检验p = 0.09和Spearman p = 0.02），而ANC<500出院的可能性与年龄、缓解状态或感染类型无关。因此，我们分别在体能状态较好或较差以及中性粒细胞减少性发热入院后住院时间多于或少于中位数时间（8天）的患者中检查了ANC与中性粒细胞减少性发热再入院之间的关系。该分析表明，只有当住院时间超过8天或体能状态<2时，出院时ANC较低的患者才更有可能再次入院。
我们的结果表明，对于因中性粒细胞减少性发热住院后的出院，ANC为500的临界值过高。ANC的上升速率及其绝对值可能也起作用。
