Novel indications for hematopoietic stem cell transplantation in inborn errors of immunity

Hematopoietic stem cell transplantation (HSCT) is a curative treatment for an expanding spectrum of inborn errors of immunity (IEI). Whilst the utility and success of this treatment is well established for common, or historically described IEI (severe combined immunodeficiency, Wiskott-Aldrich syndrome, CD40L deficiency, the role of HSCT for emerging, newly described IEI is less clear. This review examines HSCT results for recently described IEI or those in which HSCT has only recently and rarely been employed.

The literature search included HSCT in IEI from 2020 to 2025. We report the HSCT experience and outcome in newly described diseases including RIPK1, ARPC1B, CD27/CD70 deficiency. More established diseases for which HSCT has only recently been reported are described, including female carriers of X-linked chronic granulomatous disease, and X-linked agammaglobulinemia. We report on recently described diseases with limited HSCT experience including CTLA-4/LRBA deficiency, STAT1 gain-of-function. Finally, we consider diseases where HSCT has previously been considered inappropriate, like STAT3 loss-of-function.

Previous experience implies that younger age and fewer co-morbidities at time of HSCT improve outcomes, but limited natural history data combined with increased use of targeted therapies make HSCT decisions difficult in new diseases. Adoption of disease-appropriate scoring tools may aid decision making.