Late relapse of primary hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation: a consequence
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BRIEF REPORT
Late relapse of primary hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation: a consequence of low-level chimerism from a carrier donor? Amy E. Verrinder 1 & Joanna L. S. Marsden 1 & Mary A. Slatter 1,2 & Leigh McDonald 3 & Chris M. Bacon 4,5 & Joaquim Majo 4 & Andrew R. Gennery 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2019
To the editor, Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetic, rapidly progressive, life-threatening immune disorder characterized by uncontrolled, exaggerated systemic inflammation. Several autosomal recessive defects related to function of the perforin/granzymedependent cytotoxic pathway are known [1]. Mutations in genes encoding perforin, Munc 13-4, Munc 18-2, and syntaxin-11 are identified as causes of FHLH, but cases without a known genetic defect may be diagnosed based on positive family history, parental consanguinity, and refractory or recurrent HLH suggestive of a genetic predisposition [1]. Deficient cytotoxic activity of NK and T-lymphocytes is responsible for the pathological features of the disease. Failure of antigenic clearance and cytotoxicity-mediated homeostatic deletion of cytotoxic T-lymphocytes and antigen-presenting cells instigates
Amy E. Verrinder and Joanna L. S. Marsden contributed equally to this work. * Andrew R. Gennery [email protected] 1
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
2
Children’s Haematopoietic Stem Cell Transplant Unit, Great North Children’s Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Clinical Resource Building, Floor 4, Block 2, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK
3
Department of Radiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
4
Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
5
Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
a c c u m u l a t i o n o f a c t i v a t e d p o l y c l o n a l C D 8 Tlymphocytes and activated macrophages within various organs, including the central nervous system, causing a hypercytokinemic hyperinflammatory state [1, 2]. In specific situations, disease relapse can rarely follow hematopoietic stem cell transplantation (HSCT) for FHLH, usually soon after transplantation [3]. Mixed donor chimerism is tolerable, with a minimum of 20–30% donor alleles in the CD3+ compartment typically sufficient to control the disease [3]. We report an infant who required two HSCT for FHLH, specifically highlighting questions of how much donor chimerism is adequate for HSCT to be curative and whether heterozygous carrier status of the donor affects transplant outcome. The second child of a highly consanguineous family was born at term and received BCG vaccination soon after birth. At 2 months of age, after receiving the first routine immunizations, she developed fever and drowsiness with cervic
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