Late Effects After Haematopoietic Stem Cell Transplantation in patients with HLH: A Histiocyte Society, PDWP, IEWP and TCWP EBMT Study

Abstract

Background: Hematopoietic stem cell transplantation is the only curative treatment in primary hemophagocytic lymphohistiocytosis. However, hematopoietic stem cell transplantation is associated with a wide range of late effects.

Objective: Characterization of the long-term outcome and late effects following hematopoietic stem cell transplantation in primary hemophagocytic lymphohistiocytosis.

Methods: 274 children with pHLH from the EBMT registry who underwent allogeneic hematopoietic stem cell transplantation between 2004 and 2015 were included. Multivariable logistic regression models were performed to evaluate the adjusted impact of baseline variables on CNS and hormonal late effects, respectively.

Results: A broad spectrum of late effects was identified, with neurological (31%) and hormonal (34.8%) complications being the most prevalent. Chemotherapy (HLH-94/HLH04) before hematopoietic stem cell transplantation was identified as a significant risk factor for endocrinological late effects (p=0.03), highlighting a novel aspect not previously reported. The presence of neurological abnormality at diagnosis was an independent risk factor for neurological late effects (p<0.001) as was incomplete remission status at time of HCT (p=0.04).

Conclusion: Hematopoietic stem cell transplantation has significantly improved survival in primary hemophagocytic lymphohistiocytosis patients, however survivors still face significant risks of late effects.

Keywords: Primary hemophagocytic lymphohistiocytosis; familial hemophagocytic lymphohistiocytosis; hematopoietic stem cell transplantation; late effects.