Home or Away from Home: A Multi-Institution Study Comparing Medical Outcomes, Patient Perspectives, and Health-Related Quality of Life for Outpatient Versus Inpatient Management after Chemotherapy for Pediatric Acute Myeloid Leukemia
Authors: Getz Kelly D , Li Yimei , Szymczak Julia E , Aftandilian Catherine , Arnold Staci D. , Bona Kira O , Caywood Emi , Collier Anderson B. , Gramatges Maria Monica Monica , Henry Meret , Lotterman Craig , Maloney Kelly , Mian Amir , Mody Rajen , Raetz Elizabeth A. , Rubnitz Jeffrey , Verma Anupam , Winick Naomi , Wilkes Jennifer J. , Yu Jennifer C. , Fisher Brian T. , Aplenc Richard 
Published: February 2020

INTRODUCTION
Pediatric acute myeloid leukemia (AML) requires intensive chemotherapy that results in prolonged periods of neutropenia, placing patients at significant risk for life threatening infection. Current supportive care guidelines strongly recommend hospitalization after chemotherapy completion until neutrophil recovery. While approximately 70% of United States (US) centers adhere to this recommendation, there are little data to support inpatient over outpatient management. Therefore, we compared clinical outcomes (Aim 1), patient experiences (Aim 2), and patient quality of life (QoL) (Aim 3), between the two strategies in a nationally representative sample of newly diagnosed AML patients &lt;19 years old.
METHODS
Aim 1 employed retrospective, standardized chart abstraction for AML patients treated between 2011 and 2019 at 17 centers in the US. Patients were observed from their first course of chemotherapy through treatment completion, stem cell transplant, site transfer, relapse, or death. The unit of analysis was chemotherapy courses, the primary exposure was inpatient versus outpatient management, and primary outcomes were bacteremia and time to next treatment course. Only courses in which the patient met "discharge eligible" criteria were included (Figure 1). Analyses excluded Induction I given the low rate of outpatient management. Log-binomial regression was used to compare the bacteremia incidence and generalized linear regression was used to compare time to next course. Generalized estimating equations were used in overall analyses to account for correlation between courses from the same patient.
For Aim 2, patients/ families at 9 centers underwent semi-structured interviews that were transcribed and analyzed using a conventional content analysis approach (InVivo).
For Aim 3, parent proxies at 14 centers completed a PedsQL before the start of chemotherapy and then after neutrophil recovery but prior to the start of the subsequent course. Only one chemotherapy course per patient was considered. Only "discharge eligible" patients were included. Parent-proxy generic core QoL scores at the end of the chemotherapy cycle were compared by exposure group using analysis of covariance accounting for baseline scores.
RESULTS
573 patients contributed 1188 treatment courses for Aim 1 (Figure 1). Mean age was 9 ±6 years, 47% were female, and AML was classified as low, intermediate, and high risk, respectively in 65%, 4%, and 31%, respectively. Overall rates of bacteremia were not significantly different in patients receiving outpatient versus inpatient management (23.8% vs 29.0%, RR 0.76, 95% CI: 0.56, 1.03; p=0.07). Days to next course also did not differ between the groups (30.2 vs. 31.6, adjusted difference -1.6, 95% CI: -3.2, 0.5; p=0.17).
In Aim 2, 86 interviews in 57 families (39 inpatient, 18 outpatient) were performed. 86% of families receiving inpatient management expressed satisfaction and 85% receiving outpatient management expressed satisfaction. Dissatisfaction with inpatient management was driven by concerns for hospital acquired infections and separation from family. Dissatisfaction with outpatient management stemmed from stress of caring for a neutropenic child at home. Patients/families reporting satisfaction with outpatient management emphasized that the approach would not be appropriate for all families.
For Aim 3, mean (±SD) parent proxy PedsQL score did not differ between outpatient (74.3 ±18.3) and inpatient management (70.3 ±19.2), adjusted mean difference 3.95, 95% CI: -5.57, 13.5.
CONCLUSION
In this nationally representative sample of AML patients, outpatient management had bacteremia rates similar to inpatient management, with no difference in time to the start of next treatment course or patient QoL. Semi-structured interviews revealed strong alignment between patient/family satisfaction and center discharge practice. However, families experiencing outpatient management note high stress in caring for profoundly neutropenic patients at home and that this strategy would not be suitable for all families. These clinical and patient-centered results suggest that outpatient management during neutropenia is a viable approach without excess risk for children with AML. However, implementation studies are needed to identify patient/family characteristics that portend a positive experience with an outpatient strategy.

Disclosures
Raetz: Pfizer: Research Funding. Rubnitz:AbbVie: Research Funding. Fisher:Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study; Merck: Research Funding.