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Updated: Aug 12, 2026
Intrafemoral Injection of Human Hematopoietic Stem and Progenitor Cells into Immunocompromised Mice
Published on: December 8, 2023
Treating hematologic immune dysregulation in inborn errors of immunity: a real-life multicenter study
Giorgio Costagliola1, Filippo Consonni2,3,4, Riccardo Castagnoli5,6
1Section of Pediatric Hematology and Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Background:
Hematologic immune dysregulation (H-ID) - including autoimmune cytopenia (AIC), lymphoproliferation (LPD), and hemophagocytic lymphohistiocytosis (HLH) - is a potentially life-threatening manifestation of inborn errors of immunity (IEI). Despite the availability of targeted therapies, its management remains challenging, with no standardized treatment strategies established.
Objective:
To evaluate the efficacy and safety of the available treatments for H-ID, with a specific focus on the treatment indications and outcome differences between targeted versus non-targeted therapies.
Methods:
This multicentric retrospective study included 116 patients with IEI and H-ID across Italian tertiary care centers. Data included treatment indications, response rate, and incidence of adverse events (AEs).
Results:
We included patients with autoimmune lymphoproliferative immunodeficiencies (ALPID, 37.1%), humoral immunodeficiencies (31%), syndromic IEI (8.6%), and combined immunodeficiencies (8.6%). H-ID consisted of AIC (67.2%), LPD (71.6%), and HLH (9.5%). 85.3% of patients received treatment, including on-demand therapies (37.9%), long-term treatments (LTT, 84.8%), and hematopoietic stem-cell transplantation (HSCT; 9.1%). LTT included sirolimus (42.9%), mycophenolate mofetil (34.5%), rituximab (29.8%), and targeted therapies (17.9%). Sirolimus showed a higher complete response (CR) rate (61.1%), especially in ALPID patients and those with lymphoproliferation (72%). CR rate was significantly higher in patients receiving targeted therapies (80% vs 43.4%, p < 0.05). AEs were reported in 13.3% of cases, leading to drug withdrawal in 3.6%.
Conclusions:
The indications for LTT and HSCT in H-ID are still heterogeneous. Response rates are variable and influenced by the underlying diagnosis. Targeted therapies are associated with an improved response, the suboptimal molecular diagnosis rate currently limits their use.
