Reduced-Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (RICHI) (BMT CTN #1204)

HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation,
polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent
primary immune disorders that are typically fatal without Hematopoietic Cell Transplant
(HCT). However, transplant is often complicated by inflammation, infection and other
co-morbidities. In addition, these disorders have been shown to be cured with partial
chimerism, making them an ideal target for the use of reduced intensity approaches, where a
portion of patients may not achieve full donor chimerism, but instead achieve stable mixed
chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with
decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH
(Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and
unstable chimerism remain challenges. An institutional case series from Cincinnati Children's
Hospital demonstrated full or high-level chimerism and improved durable engraftment using
intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the
efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH
as well as other primary immunodeficiencies where allogeneic transplant with RIC has been
shown to be feasible and stable chimerism is curative.