Abstract
Haematopoietic stem cell transplantation currently remains the only curative treatment of primary forms of haemophagocytic lymphohistiocytosis (HLH). Rapid diagnosis, efficient primary treatment of hyperinflammation, and conditioning regimens tailored to this demanding condition have substantially improved prognosis in the past 40 years. However, refractory hyperinflammation, central nervous system (CNS) involvement, unavailability of matched donors, susceptibility to conditioning-related toxicities, and a high frequency of mixed chimaerism remain a challenge in a substantial proportion of patients. Gene therapeutic approaches for several genetic defects of primary HLH are being developed at pre-clinical and translational levels.
Highlights
Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition that may occur in a primary or secondary form
Genetic defects predisposing to primary haemophagocytic lymphohistiocytosis (HLH) are found in autosomal recessive familial HLH (FHL) 2-5, Griscelli syndrome type 2 (GS2), Chediak-Higashi syndrome (CHS), X-linked lymphoproliferative disease type 1 (XLP1), and X-linked inhibitor of apoptosis (XIAP) deficiency
haematopoietic stem cell transplantation (HSCT) with myeloablative conditioning regimens containing busulfan, cyclophosphamide, and VP16 resulted in substantial transplantation related mortality, in particular related to veno-occlusive disease (VOD) [4, 5, 17, 18]
Summary
Remission at HSCT is a key factor of survival in HLH patients. Time to transplant should be kept at a minimum, which may require alternative donors. The high prevalence of fatal veno-occlusive disease after full myeloablative busulfan-based conditioning in HLH patients has been substantially curtailed with conditioning regimens of reduced toxicity. Achieving high levels of sustainable donor chimerism in the absence of GvHD remains a challenge in HLH patients when using RIC regimens
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