Emapalumab, a fully human anti-IFNγ monoclonal antibody, has been approved in 
the US as second-line treatment of primary hemophagocytic lymphohistiocytosis 
(HLH) patients and has shown promise in patients with graft failure (GF) 
requiring a second allogeneic hematopoietic stem cell transplantation (HSCT). 
The blockade of IFNγ activity may increase the risk of severe infections, 
including fatal mycobacteriosis. We report a case of secondary HLH-related GF in 
the context of HLA-haploidentical HSCT successfully treated with emapalumab in 
the presence of concomitant life-threatening infections, including disseminated 
tuberculosis (TB). A 4 years old girl with Adenosine Deaminase-Severe Combined 
Immunodeficiency complicated by disseminated TB came to our attention for 
ex-vivo hematopoietic stem cell-gene therapy. After engraftment failure of gene 
corrected cells, she received two HLA-haploidentical T-cell depleted HSCT from 
the father, both failed due to GF related to concomitant multiple infections and 
secondary HLH. Emapalumab administration allowed to control HLH, as well as to 
prevent GF after a third haplo-HSCT from the mother. Remarkably, all infections 
improved with antimicrobial medications and disseminated TB did not show any 
reactivation. This seminal case supports emapalumab use for treatment of 
secondary HLH and prevention of GF in patients undergoing haplo-HSCT even in the 
presence of multiple infections, including TB.