Modified G-CSF/ATG-Based Haploidentical Transplantation Protocol in Pediatric Primary Hemophagocytic Lymphohistiocytosis: A Long-Term Follow-Up Single-Center Experience

Background: Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by immune dysregulation. Hematopoietic stem cell transplantation (HSCT) represents the only option for long-term cure for primary HLH. However, only around 25% of patients have a fully HLA-matched donor.

Methods: In this retrospective study, we analyzed 42 pediatric patients with primary HLH who underwent haplo-SCT using the modified granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol. The conditioning regimen included 300-600 mg/m² etoposide (VP16), along with low doses of busulfan (Bu) (0.8-1.2 mg/kg every 6 hours on Days -8 to -6), cyclophosphamide (Cy) (10 mg/kg/day on Days -4 to -3), fludarabine (Flu) (30 mg/m²/day on Days -5 to -3), and ATG (8-9 mg/kg total dose on Days -5 to -2) to reduce complications.

Results: All 42 patients achieved successful engraftment. Following a median follow-up period of 48.7 months, 32 of the 42 patients remained alive and disease free. The 2-year overall survival (OS) rate was 78.4%, and the 5-year OS rate was 73.7%. The 2-year failure-free survival (FFS) rate was 71.3%, and the 5-year FFS rate was 66.5%. Patients who achieved complete remission at the time of HSCT showed better OS (p < 0.05). The incidence of Grade III-IV acute graft-versus-host disease (GVHD) was 26.2%, and severe chronic GVHD was observed in 11.9% of patients. Thrombotic microangiopathy occurred in 13 patients, and veno-occlusive disease in two patients.

Conclusions: This modified G-CSF/ATG-based haploidentical protocol demonstrates significant potential for pediatric patients with primary HLH, exhibiting commendable effectiveness and safety.