Secondary Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome Following Allo-HCT: Features,...

Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a rare but highly fatal complication after allogeneic hematopoietic cell transplantation (allo-HCT), frequently diagnosed under conditions of clinical uncertainty. We aimed to characterize post-transplant sHLH/MAS and to identify clinically accessible factors associated with early mortality.

We retrospectively analyzed adult patients who developed sHLH/MAS after allo-HCT between 2018 and 2025. Inclusion required an HScore ≥ 169. Overall survival within 60 days from sHLH/MAS onset was the primary endpoint. Clinical and laboratory variables were evaluated using Cox proportional-hazards models, and patients were stratified according to the number of adverse prognostic factors identified.

Seventy-two patients met inclusion criteria. Median time from allo-HCT to sHLH/MAS onset was 22 days. Sixty-day overall survival was poor. In univariable and multivariable analyses, vasopressor-dependent sepsis (HR 7.77, p < 0.001) and ferritin > 15 000 μg/L (HR 3.48, p = 0.002) were independently associated with early mortality. Stratification based on these two factors separated patients into low-, intermediate-, and high-risk groups with 60-day survival of 92%, 52%, and 9%, respectively (p < 0.001).

Post-transplant sHLH/MAS is associated with extremely high early mortality. Vasopressor-dependent sepsis and extreme hyperferritinemia identify patients at particularly high risk. These findings require confirmation in independent cohorts.