Date Published: March 20, 2019
Publisher: Public Library of Science
Author(s): Raïsa Carmen, Galit B. Yom-Tov, Inneke Van Nieuwenhuyse, Bram Foubert, Yishai Ofran, Ana Paula Arez.
Patients with hematological malignancies are susceptible to life-threatening infections after chemotherapy. The current study aimed to evaluate whether management of such patients in dedicated inpatient and emergency wards could provide superior infection prevention and outcome.
We have developed an approach allowing to retrieve infection-related information from unstructured electronic medical records of a tertiary center. Data on 2,330 adults receiving 13,529 chemotherapy treatments for hematological malignancies were identified and assessed. Infection and mortality hazard rates were calculated with multivariate models. Patients were randomly divided into 80:20 training and validation cohorts. To develop patient-tailored risk-prediction models, several machine-learning methods were compared using area under the curve (AUC).
Of the tested algorithms, the probit model was found to most accurately predict the evaluated hazards and was implemented in an online calculator. The infection-prediction model identified risk factors for infection based on patient characteristics, treatment and history. Observation of patients with a high predicted infection risk in general wards appeared to increase their infection hazard (p = 0.009) compared to similar patients observed in hematology units. The mortality-risk model demonstrated that for infection events starting at home, admission through hematology services was associated with a lower mortality hazard compared to admission through the general emergency department (p = 0.007). Both models show that dedicated hematological facilities and emergency services improve patient outcome post-chemotherapy. The calculated numbers needed to treat were 30.27 and 31.08 for the dedicated emergency and observation facilities, respectively. Infection hazard risks were found to be non-monotonic in time.
The accuracy of the proposed mortality and infection risk-prediction models was high, with the AUC of 0.74 and 0.83, respectively. Our results demonstrate that temporal assessment of patient risks is feasible. This may enable physicians to move from one-point decision-making to a continuous dynamic observation, allowing a more flexible and patient-tailored admission policy.
Patients with hematological malignancies are known to be highly susceptible to infections, since the disease and/or therapy significantly weaken their immune system, leading to considerable infection-related mortality[1,2,3]. While the past decade has witnessed significant advances in treatment strategies for hematological cancers, prevention, and adequate management of infections still pose a major challenge. In a large retrospective study of more than 41,000 cancer patients admitted due to a suspected infection, mortality rates among those who were treated for leukemia, lymphoma, and myeloma were as high as 14.3%, 8.9%, and 8.2%, respectively. Although for some patients with neutropenia developing during therapy for solid tumors, ambulatory treatment was reported to be safe, this could not be extrapolated to high-risk patients with hematological malignancies. Presently, there are no clear guidelines for the identification of hemato-oncological patients who could be treated in the ambulatory setting during post-chemotherapy neutropenia and who should be hospitalized either in a general internal medicine ward (GW), or in a hematological facility. In reality, the shortage of dedicated beds and economical restrictions provide an incentive for minimizing hospital stay. Obviously, patients with active life-threatening infections or other similar conditions should be admitted to hospital; however, many centers are re-evaluating their current practice in an attempt to reduce the number of “non-essential” hospitalizations. Commonly, in high-risk situations (e.g., induction therapy for acute leukemia), physicians choose to keep patients in the hospital for observation after completion of chemotherapy until the recovery of white blood cell (WBC) counts to ensure that immediate measures are taken in case of infection development. However, due to limited bed availability in Hematology Wards (HW), some patients are observed in GWs, or are discharged home shortly after chemotherapy completion. At multiple medical centers, discharged patients that developed fever or other signs of infection at home, receive emergency care at the Hematology Outpatient Clinic (HOutC) during morning hours on weekdays, whereas in the afternoon, at night, and during weekends, such patients are referred to the General Emergency Department (ED).
The study was approved by the Institutional Review Board (Approval #066-14RMB), and was conducted in accordance with the Declaration of Helsinki. A waiver of patient informed consent was granted as it was a retrospective chart review study.
Among multiple toxicities and risks associated with intensive chemotherapy for hematological malignancies, life-threatening infection events are extremely common. This justifies the definition of patients suffering from these diseases as a population at risk that requires special considerations. The present study has demonstrated that patients treated for malignant hematological conditions have a better outcome when they are managed in specialized units. This is true both of observation upon chemotherapy completion and emergency treatment if an infection event occurs after discharge from hospital. Due to the shortage of such dedicated facilities, the identification of the patients who would benefit most from management in these wards is critical.