Clinical Management of Relapsed/Refractory Hemophagocytic Lymphohistiocytosis in Adult Patients: A Review of Current Strategies and Emerging Therapies.

Introduction: Haemophagocytic lymphohistiocytosis (HLH) is a severe disorder with high mortality. The aim of this review is to update clinical management of relapsed/refractory HLH in adults, with a focus on current and new therapies.

Methods: We searched relevant articles in Embase and PUBMED with the MESH term "hemophagocytic lymphohistiocytosis; refractory; relapsing; adult."

Results: One hundred eight papers were found; of these, 22 were retained for this review. The treatment of HLH in adult is based on the HLH-94 regimen. The response rate is lower than in pediatric patients, and 20-30% are refractory to this therapy. DEP regimen and allogenic hematopoietic stem cell transplantation (HSCT) are associated with complete response and partial response in 27% and 49.2%, respectively. However, many patients fail to achieve a stable condition before HSCT, and mortality is higher in them. New drugs have been developed, such as emapalumab, ruxolitinib, and alemtuzumab, and they may be used as bridges to the curative HSCT. They are relatively well tolerated and have few or mild side effects. With these agents, the rate of partial response ranges from 14.2% to 100%, while the rate of complete response is highly variable according to study and medication used. The number of patients who achieved HSCT ranged from 44.8% to 77%, with a survival rate of 55.9% to 100%. However, the populations in these studies are mainly composed of mixed-age patients (pediatric and adult patients), and studies including only adult patients are scarce.

Conclusion: Relapsed or refractory HLH in adult patients is associated with poor outcome, and consolidation with HSCT may be required in some cases. Mortality related to HSCT is mainly due to active HLH disease before HSCT and post HSCT complications. New drugs, such as empalumab, ruxolitinib, and alemtuzumab are interesting since these agents may be used as bridges to HSCT with increases in the numbers of patients proceeding to HSCT and survival rate.