Pre-Transplant Immune Dysregulation Predicts for Poor Outcome Following Allogeneic Haematopoietic Stem Cell Transplantation in Adolescents and Adults with Inborn Errors of Immunity (IEI)

J Clin Immunol. 2025 Jan 6;45(1):64. doi: 10.1007/s10875-024-01854-y.

Abstract

Allogeneic haematopoietic stem cell transplantation (alloHSCT) is safe and effective for adolescents and adults with inborn errors of immunity (IEI) with severe disease manifestations of their disease. The haematopoietic cell transplantation comorbidity index (HCT-CI) score predicts transplant survival in non-malignant diseases, including IEIs. We hypothesised that immune dysregulation pre-transplant may also influence transplant outcomes. We calculated the pre-transplant immune dysregulation and disease activity score (IDDA v2.1) for 82 adolescent and adult IEI patients (aged ≥ 13 years). Three-year overall survival (OS) for the whole cohort was 90% (n = 82) with a median follow up of 44.7 months (range 8.4 to 225.8). Events were defined as acute graft-versus-host disease (GvHD) grades II or above, chronic GvHD of any grade, graft failure, or death from any cause. Three-year event free survival (EFS) for the whole cohort was 72%. In multivariable analysis the IDDA v2.1 score pre-transplant and HCT-CI score significantly impacted OS (hazard ratio 1.08, p = 0.028) and EFS (hazard ratio 1.04, p = 0.0005). Importantly, 35% of this cohort had a high IDDA v2.1 score (≥ 15) and low HCT-CI score (< 3) suggesting that the risks of alloHSCT may be underestimated in a proportion of patients with IEI if the HCT-CI score is used alone. These findings support the potential for improved outcomes following successful modulation of immune dysregulation pre-transplant. The IDDA v2.1 score has utility as an objective measurement of pre-transplant immune dysregulation providing additional information reagrding the risks and potential complications of alloHSCT in an individual IEI patient.

Keywords: Inborn errors of immunity; Stem cell transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immune System Diseases / diagnosis
  • Immune System Diseases / etiology
  • Immune System Diseases / mortality
  • Immune System Diseases / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Transplantation, Homologous*
  • Treatment Outcome
  • Young Adult