Graft rejection markers in children undergoing hematopoietic cell transplant for bone marrow failure

Abstract

Graft rejection (GR) is a poorly understood complication of hematopoietic cell transplant (HCT). GR risk factors are well-published, but there are no reliable biomarkers or therapies known. Fever is the most common symptom of GR but no study has evaluated fever kinetics as a diagnostic marker of GR. The objectives of this study were to identify mechanisms, biomarkers and potential therapies for GR after HCT. Chemokine ligand 9 (CXCL9), b-cell activating factor (BAFF) and complement markers (sC5b-9, C3a and C5a) were measured in 7 GR patients and compared to 15 HCT controls. All patients had a diagnosis of aplastic anemia, Fanconi anemia or genetically undefined chromosomal fragility syndrome. All GR patients were febrile during GR, therefore control HCT patients were matched for diagnosis and early fevers after HCT. GR patients had significantly higher CXCL9, BAFF and sC5b-9 at the time of fever and GR compared to control HCT patients at the time of fever. The maximum fever was significantly higher and occurred significantly later in the transplant course in GR patients compared to febrile HCT controls. These data support the use of CXCL9, BAFF, sC5b-9 and fever kinetics as GR markers. Two GR patients underwent a 2nd HCT that was complicated by high fevers. Both patients received interferon and complement blockers during their 2nd HCT and both preserved their graft. These laboratory and clinical findings support larger studies to evaluate the safety and efficacy of interferon, complement and BAFF inhibitors for the prevention and treatment of GR after HCT.

Human STAT1 gain of function with chronic mucocutaneous candidiasis: A comprehensive review for strengthening the connection between bedside observations and laboratory research

“…Additionally, a case report involving a patient with STAT1 GOF suggested the therapeutic potential of emapalumab, an IFN‐γ blocker, during HSCT 140 . While HSCT presents a potential curable option for STAT1 GOF, it is also associated with a high risk of secondary graft failure, likely due to increased levels of IFN‐γ 78,140–142 . Kunvarjee et al 140 .…”