Secondary haemophagocytic lymphohistiocytosis (sHLH), also known as Macrophage Activation Syndrome (MAS), is identified as a severe and life-threatening hyperinflammatory condition. This syndrome can emerge in individuals suffering from severe infections, malignancies, or autoimmune disorders. Furthermore, it is recognized as a rare yet critical complication associated with haematopoietic stem cell transplantation (HSCT), often leading to high mortality rates. In allogeneic HSCT scenarios, it may be linked to graft versus host disease. Reports also indicate its occurrence after CAR-T cell therapy, though distinguishing it from cytokine release syndrome (CRS) presents significant diagnostic challenges. This article aims to summarise current literature and share findings from a survey conducted across EBMT-affiliated centers, focusing on the awareness and management practices for sHLH/MAS post-HSCT and CAR-T cell therapy.
The methodology employed in this study involved an online questionnaire distributed to principal investigators across EBMT member transplant centers that manage adult patients (18 years and older). The survey sought to gather data on several key aspects, including the number of sHLH/MAS cases encountered at their centers over a three-year period (2016-2018), the screening protocols in place, the utilization of existing diagnostic and classification criteria, and the treatment protocols followed.
The study garnered responses from 114 out of 472 centers, representing 24 countries. The data collected revealed estimated sHLH/MAS rates of 1.09% (95% CI = 0.89-1.30) following allogeneic HSCT, 0.15% (95% CI = 0.09-5.89) after autologous HSCT, and notably higher at 3.48% (95% CI = 0.95-6.01) following CAR-T cell therapy. A significant majority of the participating centers, approximately 70%, reported not adhering to a standard screening protocol for sHLH/MAS. Among those that did screen, serum ferritin levels were the most frequently used marker, utilized by 78% of centers. Other markers included soluble IL-2 receptor (24%), triglycerides (15%), and fibrinogen (11%). There was considerable variability in what was considered a “clinically significant” level of serum ferritin, with thresholds ranging from 500 to 10,000 μg/mL. In terms of diagnostic criteria, the HLH-2004 criteria were most commonly employed (43%), followed by the H score (15%). A substantial 80% of respondents indicated the absence of a standard management protocol at their centers, with treatments typically involving combinations of corticosteroids, chemotherapeutic agents, cytokine blockade, and monoclonal antibodies.
In conclusion, the survey highlights a significant inconsistency in approaches to screening, diagnosis, and management of sHLH/MAS across EBMT centers. This variability underscores the urgent need for further research to enhance awareness and establish harmonized, evidence-based strategies for the recognition and treatment of sHLH/MAS in patients undergoing HSCT and CAR-T cell therapy. The findings call for collaborative efforts to standardize practices and improve patient outcomes in these complex clinical scenarios.
