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

Maria L Taylor; Kacie J Hoyt; Joseph Han; Leslie Benson; Siobhan Case; Mia T Chandler; Margaret H Chang; Craig Platt; Ezra M Cohen; Megan Day-Lewis; Fatma Dedeoglu; Mark Gorman; Jonathan S Hausmann; Erin Janssen; Pui Y Lee; Jeffrey Lo; Gregory P Priebe; Mindy S Lo; Esra Meidan; Peter A Nigrovic; Jordan E Roberts; Mary Beth F Son; Robert P Sundel; Maria Alfieri; Jenny Chan Yeun; Damilola M Shobiye; Barbara Degar; Joyce C Chang; Olha Halyabar; Melissa M Hazen; Lauren A Henderson

doi:10.3899/jrheum.211219

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

J Rheumatol. 2022 Sep;49(9):1042-1051. doi: 10.3899/jrheum.211219. Epub 2022 Jul 15.

Authors

Maria L Taylor¹, Kacie J Hoyt², Joseph Han³, Leslie Benson⁴, Siobhan Case⁵, Mia T Chandler¹, Margaret H Chang⁵, Craig Platt¹, Ezra M Cohen¹, Megan Day-Lewis¹, Fatma Dedeoglu¹, Mark Gorman⁴, Jonathan S Hausmann⁶, Erin Janssen¹, Pui Y Lee¹, Jeffrey Lo¹, Gregory P Priebe⁷, Mindy S Lo¹, Esra Meidan¹, Peter A Nigrovic⁵, Jordan E Roberts¹, Mary Beth F Son¹, Robert P Sundel¹, Maria Alfieri⁸, Jenny Chan Yeun⁸, Damilola M Shobiye⁸, Barbara Degar⁹, Joyce C Chang¹, Olha Halyabar¹, Melissa M Hazen¹, Lauren A Henderson¹⁰

Affiliations

¹ M.L. Taylor, BS, M.T. Chandler, MD, C. Platt, MD, PhD, E.M. Cohen, MD, M. Day-Lewis, RN, MSN, CPNP, F. Dedeoglu, MD, E. Janssen, MD, PhD, P.Y. Lee, MD, PhD, J. Lo, MD, M.S. Lo, MD, PhD, E. Meidan, MD, J.E. Roberts, MD, M.B.F. Son, MD, R.P. Sundel, MD, J.C. Chang, MD, MSCE, O. Halyabar, MD, M.M. Hazen, MD, L.A. Henderson, MD, MMSc, Division of Immunology, Boston Children's Hospital, Boston, Massachusetts.
² K.J. Hoyt, MSc, Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
³ J. Han, BS, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ L. Benson, MD, M. Gorman, MD, Division of Neurology, Boston Children's Hospital, Boston, Massachusetts.
⁵ S. Case, MD, M.H. Chang, MD, PhD, P.A. Nigrovic, MD, Division of Immunology, Boston Children's Hospital, and Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts.
⁶ J.S. Hausmann, MD, Division of Immunology, Boston Children's Hospital, and Division of Rheumatology and Clinical Immunology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
⁷ G.P. Priebe, MD, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.
⁸ M. Alfieri, MPH, J. Chan Yeun, MSPH, D.M. Shobiye, MPH, Department of Pediatric Quality Program, Boston Children's Hospital, Boston, Massachusetts.
⁹ B. Degar, MD, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹⁰ M.L. Taylor, BS, M.T. Chandler, MD, C. Platt, MD, PhD, E.M. Cohen, MD, M. Day-Lewis, RN, MSN, CPNP, F. Dedeoglu, MD, E. Janssen, MD, PhD, P.Y. Lee, MD, PhD, J. Lo, MD, M.S. Lo, MD, PhD, E. Meidan, MD, J.E. Roberts, MD, M.B.F. Son, MD, R.P. Sundel, MD, J.C. Chang, MD, MSCE, O. Halyabar, MD, M.M. Hazen, MD, L.A. Henderson, MD, MMSc, Division of Immunology, Boston Children's Hospital, Boston, Massachusetts; Lauren.Henderson@childrens.harvard.edu.

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.

Keywords: hemophagocytic lymphohistiocytosis; macrophage activation syndrome.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Biomarkers
C-Reactive Protein
Child
Humans
Lymphohistiocytosis, Hemophagocytic* / therapy
Macrophage Activation Syndrome* / diagnosis
Macrophage Activation Syndrome* / drug therapy
Retrospective Studies

Substances

C-Reactive Protein
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding