New Evidence-Based Protocol Reduces Morbidity and Mortality in HLH/MAS

Introduction : Hemophagocytic lymphohistiocytosis (HLH)/ Macrophage activation syndrome ( MAS ) is alife-threatening condition if not diagnosed and treated effectively . The condition is characterized by an uncontrolled hyperinflammatory response which is often triggered by infections/ malignancy or connective tissue disorders . Familial types result from genetic defects in natural killer cells and cytotoxic T-cells, typically affecting perforin and intracellular vesicles. HLH is likely under- recognized which contributes to its high morbidity and mortality. Early recognition and effective therapy is crucial for cure . Methods : We conducted a literature review and developed an evidence-based practice protocol following the KSUMC Evidence-Based Guidelines and Protocols Program. The protocol was revised with input from key stakeholders to align with the needs of our academic healthcare center. This approach has significantly improved the morbidity and mortality of pediatric patients with HLH. Results : Boston children’s hospital Results : After the EBG launch in, 17 patients were diagnosed with MAS-HLH by the treating team. Of these 94% met criteria for MAS. 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. Initial KSUMC Results : After the EBG launch in, nine children were confirmed to be HLH/MAS as per KSUMC HLH/MAS criteria , of those the survival rate was 88.9 % . The one death was mostly due to refractory/relapsed ALL . Time to reach the diagnosis was 6-13 days of admission , response to treatment started around 2-3 days of treatment . Treatment was tailored as per the protocol , most of cases received IVIG , anakinra and prednisolone . References 1-Amer YS, Wahabi HA, Abou Elkheir MM, Bawazeer GA, Iqbal SM, Titi MA, Ekhzaimy A, Alswat KA, Alzeidan RA, Al-Ansary LA. Adapting evidence- based clinical practice guidelines at university teaching hospitals: A model for the Eastern Mediterranean Region. J Eval Clin Pract. 2019 Aug;25(4):550-560. https://doi.org/10.1111/jep.12927 2-Halyabar, O., Chang, M.H., Schoettler, M.L. et al. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Pediatr Rheumatol 17, 7 (2019). https://doi.org/10.1186/s12969-019- 0309-6 14.2. 3- Qing Zhang, Yun-Ze Zhao, Hong-Hao Ma .et Al , A study of ruxolitinib response–based stratified treatment for pediatric hemophagocytic lymphohistiocytosishttps . Blood (2022) 139 (24): 3493–3504. https://doi.org/10.1182/blood.2021014860 4- Maria L Taylor et al. J , An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome , Rheumato , 2022 Sep;49(9):1042-1051.