Fever and Neutropenia Management and Infectious Prevention Strategies in Children with Severe or Very Severe Aplastic Anemia: A North American Pediatric Aplastic Anemia Consortium (NAPAAC) Study

Introduction: Evidence-based clinical practice guidelines (CPGs) exist for supportive care interventions including fever and neutropenia (FN), infection prevention for children with cancer, however FN management in benign hematological conditions specifically for conditions with bone marrow failure (BMF) is not standardized. Pediatric Severe Aplastic Anemia (sAA) is an acquired BMF which develops severe and prolonged neutropenia. Data regarding FN management and infection prevention strategies in this population are lacking to inform best practices.

Objective: Evaluate current practices across 53 centers participating in the North American Pediatric Aplastic Anemia Consortium (NAPAAC) regarding FN management and infection prevention strategies in pediatric patients with sAA or very severe aplastic anemia (vsAA).

Method: A RedCap survey was created and electronically distributed to the 53 NAPAAC institutions. The instrument consisted of the following domains: 1. Participant demographics; 2. Institutional practices for usage of vascular catheters; FN management; Infectious Disease (ID) screening and prevention strategies, including isolation precautions, hand-hygiene and vaccination practices, and education around mitigating infection risk in pediatric patients with sAA/ vsAA. Pediatric patients were defined as individuals 0 to 18 years of age who had not received a HCT and met standard diagnostic criteria for sAA/ vsAA. Each institution was asked to submit one collective survey from June 1, 2022 through July 16, 2022. Descriptive analyses were performed.

Results: In total 43 (81%) NAPAAC sites completed the survey. The participant demographics were as follows: 68% (N=29) hematologists, 30% (N=13) HCT specialists, 2% (N=1) practiced as both. Most centers diagnosed 0 to 5 new sAA/vsAA cases/ year (N=28, 65%), 3 (7%) centers diagnosed ≥11/yr. With regards to central venous catheter (CVC) utilization, 32 (74%) of centers report ≥50% of their sAA patients have a CVC placed with a majority being placed at time of anti-thymocyte globulin initiation. The preferred CVC is a peripheral intravenous central catheter (PICC, N=24, 56%) followed by an implantable CVCs (N=17, 40%). Thirteen (30%) centers had a FN CPG specific to sAA/vsAA. An additional 28 (65%) centers report using a FN CPG adapted from the management of children with malignancy. In hemodynamically stable sAA with FN, the majority of respondents prescribe empiric monotherapy with cefepime (N=36, 84%). In hemodynamically unstable FN, either vancomycin plus an anti-pseudomonal Beta-lactam (APBL) (N=30, 71%) or triple combination with vancomycin, APBL, and aminoglycoside (N=6, 14%) are prescribed. Empiric antifungals are not routinely prescribed in stable FN sAA (N=28, 70%) though 19 (48%) centers would start empiric antifungals in hemodynamically unstable sAA patients, including echinocandins (N=8, 42%), mold-active azoles (N=6, 32%), or amphotericin (N=3, 16%). Furthermore, 42% of participants reported that adequate criteria for discontinuation of FN antibiotics and discharge in clinically stable patients with sterile cultures was afebrile status for > 24 hours for both sAA and vsAA patients, regardless of ANC.

Prior to the COVID-19 pandemic, centers were divided on recommendations for patients to wear a surgical mask (N=24, 43%) to outpatient clinic visits or not (N=19, 44%). 95% of institutions routinely discussed safe living and ID prevention (Table 1), though only 16 (37%) provided written education. 86% of respondents report reviewing vaccinations in all sAA /vsAA at diagnosis. Only 12 (34%) provided non-influenza, inactivated vaccines to incompletely immunized patients. Lastly, 37 (97%) of respondents provided inactivated influenza vaccine to sAA/vsAA in their clinics and 39 (93%) recommend and 27 (73%) provided COVID-19 mRNA vaccination in their clinics. 7 centers (16%) performed SARSCoV2 antibody testing to inform need for initial or booster COVID-19 vaccination.

Conclusion: Most NAPAAC centers applied malignancy driven CPGs to manage FN in sAA/vsAA patients. Other infection control/prevention strategies were quite variable, including use of masks, education around topics related to infectious risk mitigation, and vaccination practices. Variation in supportive care practices in this population highlights an urgent need for quality improvement initiatives to develop evidence-based CPGs.

Rothman:bluebird bio: Research Funding; Novartis: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.