LETTER TO EDITOR Successful Matched Related Bone Marrow Transplantation in a Patient with Autosomal Dominant Interferon Gamma Receptor 1 Deficiency Christa S. Zerbe 1 & Dimana Dimitrova 2 & Juan J. Gea-Banacloche 3 & Samantha Kreuzburg 1 & Steven M. Holland 1 & Jennifer A. Kanakry 2 Received: 27 May 2020 /Accepted: 9 July 2020 # This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020 Abstract Summary This is a report of a successful bone marrow transplant in an IFN-γR1 patient with progressive mycobacterial infection. Purpose Hematopoietic cell transplant in patients with interferon gamma receptor deficiencies has been fraught with challenges, not the least of which is failure of engraftment and infectious complications. Methods This is a report of a successful hematopoietic cell transplant in an actively infected patient of advanced age. Results This case report shows successful engraftment and resolution of infection posttransplant using a matched related donor in a single institution. Conclusion A successful curative HCT despite persistent, disseminated, nontuberculous mycobacterial infection in a patient with AD-IFNγR1 suggests that this approach, while difficult, may be useful in other patients with otherwise refractory disease. Keywords Interferon gamma receptor . hematopoietic cell transplant . nontuberculous mycobacteria . infection To the Editor The interferon-γ pathway plays a critical role in the innate response to intracellular infection. The increased susceptibility to mycobacterial infections has been shown to be associated with defects in signaling through the interferon-γ receptor. Patients with autosomal dominant interferon gamma receptor 1 deficiency (AD-IFNγR1) have reduced signaling through the interferon- γ receptor leading to susceptibility to nontuberculous mycobacteria (NTM), among other organ- isms. In contrast to patients with complete IFNγ receptor de- ficiency who present in infancy and early childhood, patients with autosomal dominant IFNγR1 deficiency typically present in later childhood through early adulthood with infec- tion. Hematopoietic cell transplantation (HCT) is poten- tially curative yet historically very difficult in the com- plete receptor deficiency population [1–6]. Roesler et al. looked at eight patients with complete IFN-γR1 deficien- cy who received a total of 11 HCTs, mostly myeloablative, 10 from matched related donors, and 1 from an HLA-haploidentical parent. They found only 3 curative outcomes with the others characterized by prima- ry or secondary graft failure or high mortality [1]. Much of the high mortality was related to mycobacterial infec- tion despite full donor chimerism, an illustration of the challenges in transplanting these patients, even after en- graftment. These case series describe patients with com- plete receptor loss, but there are no data for HCT in AD IFN-γR1. Given the mortality surrounding active and pretransplant infection, this case demonstrates successful recovery after an immune reconstitution inflammatory syndrome [7]. We report successful engraftment and phe- notype reversal following reduced intensity conditioning (RIC), HLA-matched sibling donor (MSD), and HCT in a patient with AD IFN-γR1 with progressive disseminated Mycobacterium avium X-cluster infection. * Christa S. Zerbe zerbech@niaid.nih.gov 1 Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 2 Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 3 Mayo Clinic, Phoenix, AZ, USA Journal of Clinical Immunology https://doi.org/10.1007/s10875-020-00826-2