An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome

Abstract

Objective To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG). Methods A management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods. Predetermined outcome metrics were evaluated in the 2 cohorts. Results After the EBG launch, 57 children were identified by house staff as potential patients with MAS-HLH, and rheumatology was consulted for management. Ultimately, 17 patients were diagnosed with MAS-HLH by the treating team. Of these, 59% met HLH 2004 criteria, and 94% met 2016 classification criteria for MAS complicating systemic juvenile idiopathic arthritis. There was a statistically significant reduction in mortality from 50% before implementation of the EBG to 6% in the post-EBG cohort (P = 0.02). There was a significant improvement in time to 50% reduction in C-reactive protein level in the post-EBG vs pre-EBG cohorts (log-rank P < 0.01). There were trends toward faster time to MAS-HLH diagnosis, faster initiation of immunosuppressive therapy, shorter length of hospital stay, and more rapid normalization of MAS-HLH–related biomarkers in the patients post-EBG. Conclusion While the observed improvements may be partially attributed to advances in treatment of MAS-HLH that have accumulated over time, this analysis also suggests that a multidisciplinary treatment pathway for MAS-HLH contributed meaningfully to favorable patient outcomes.

Dr. Degar et al reply

“…Rousset and Ray for their comment 1 on our manuscript and for highlighting the importance of a consensus-driven, multidisciplinary approach to the management of patients with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). 2 As Rousset and Ray note, 1 the nature of MAS-HLH lends itself to the need for input from many subspecialties and a predetermined approach to the diagnosis and treatment of affected patients. The presentation of MAS-HLH can be pleomorphic, ranging from the classic presentation of multisystem dysfunction to organ-specific manifestations such as central nervous system (CNS)-isolated HLH.…”

“…Rousset and Ray note several features of their multidisciplinary team for MAS-HLH that were also important for success at our institution. 2,9 The first is continued engagement of a group of pediatric subspecialities with an interest and expertise in MAS-HLH. Second, this MAS-HLH workgroup developed consensus on a diagnostic and treatment approach for patients with MAS-HLH that was workable at their institution.…”

Implementing a Disease-specific Multidisciplinary Team and Order Set for Hemophagocytic Lymphohistiocytosis in a Pediatric Hospital

“…One study performed by Boston Children’s Hospital focused on the development of a collaborative approach to the diagnosis and management of HLH/MAS and supported the incorporation of multidisciplinary work groups to reduce treatment variation and improve outcomes 11 . Subsequently, the implementation of multidisciplinary, evidence-based guidelines for HLH/MAS was found to be associated with improved clinical outcomes, including decreased mortality 12 . Thus, it seems that a multidisciplinary team consisting of subspecialists is necessary to provide patients with a full spectrum of treatment options and the appropriate supportive care.…”

Improving Outcomes for Patients With Hemophagocytic Lymphohistiocytosis

“…We note a recent study by Taylor et al that addressed the challenge of managing macrophage activation syndrome and HLH within an academic hospital institution through implementation of evidence-based guidelines that were established by consensus across multiple pediatric subspecialties. 4 The described approach to the diagnosis and management of HLH by this hospital institution prompted us to take this opportunity to describe our preliminary findings of implementing a disease-specific multidisciplinary workgroup at Cook Children's Medical Center (CCMC).…”

“…Disease-specific workgroups within a nonacademic institution are unique from those established in an academic institution, as nonacademic institutions do not have residents or fellows to support the group and, generally, there is limited funding for research and resources when compared to an academic institution. Considering the recent study finding associated improved clinical outcomes for children with HLH after the implementation of a streamlined approach to HLH, 4 it is relevant to investigate the outcomes at other institutions. We hope to reinforce the importance of developing a collaborative approach to the diagnosis and management of HLH.…”