Hemophagocytic lymphohistiocytosis syndromes (HLH) is one of the warning signs of inborn errors of immunity (IEI) and can be either primary, due to a cytotoxicity defect, or secondary. Hematopoietic stem cell transplantation (HSCT) is a key treatment, particularly for primary HLH.
To assess HSCT outcomes in patients with IEI-associated HLH at the National Centre for Bone Marrow Transplantation in Tunis.
This retrospective longitudinal cohort study was conducted in the Pediatric Immuno-Haematology and Haematopoietic Stem Cell Transplant Department in Tunisia over 18 years (2005–2022). It included patients with IEI who developed HLH and underwent HSCT. Conditioning regimen, complications definition, and management were conducted according to the 2019 EBMT definitions.
Thirteen patients underwent HSCT, with a median delay of 4 months (Q1 = 3, Q3 = 4.7) from HLH episode. Nine had primary cytotoxicity defects: FHL (n = 2), immunodeficiency with hypopigmentation (n = 3), EBV susceptibility (n = 2), and unclassified HLH (n = 2). Four had secondary HLH due to other IEIs: ADA2 deficiency (n = 1), CID (n = 1), CGD (n = 1), and LRBA deficiency (n = 1). The transplant was geno-identical in seven cases and haplo-identical in six. Before HSCT, seven patients were in complete remission and five in partial remission. All patients received reduced-intensity conditioning, mainly fludarabine with IV busulfan (67%). GVHD prophylaxis included cyclosporine (n = 13), MMF (n = 6), methotrexate (n = 7) and post-transplant T cell depletion (n = 6). No primary graft rejection occurred. Neutrophil engraftment was achieved after 25 days (Q1 = 16, Q3 = 28). Post-transplant complications included bacterial (n = 5) and viral (n = 3) infections, acute GVHD (n = 7), and endothelial complications (n = 11). At the last follow-up, 10 patients achieved durable remission, while 3 died from septic shock (n = 2) and severe veno-occlusive disease (n = 1).
Hematopoietic stem cell transplantation is an effective treatment for IEI-associated HLH. It carries risks of infections, GVHD, and endothelial complications. Early identification and timely HSCT are crucial for improving survival in these high-risk patients.
