Treating hematologic immune dysregulation in inborn errors of immunity: a real-life multicenter study.

Authors

Giorgio Costagliola, Filippo Consonni, Riccardo Castagnoli, Mayla Sgrulletti, Eleonora Gambineri, Giuliana Giardino, Federica Cavone, Davide Montin, Francesca Conti, Baldassarre Martire, Matteo Chinello, Irene D'Alba, Francesco Saettini, Adele Civino, Gian Luigi Marseglia, Roberta Romano, Beatrice Rivalta, Fabiola Guerra, Emilia Cirillo, Lucia Pacillo, Francesca Cillo, Laura Grilli, Federico Diomeda, Mattia Moratti, Francesca Robasto, Caterina Cancrini, Gabriella Casazza, Claudio Pignata, Viviana Moschese, Rita Consolini

Published in

Frontiers in immunology. Volume 17. Pages 1854044. Epub Jul 27, 2026.

Abstract

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.
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.
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).
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%.
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.

PMID:
42577193
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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