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EBMT 2019 | Treatment of steroid-resistant gastrointestinal graft-versus­-host disease using α1-antitrypsin

Apr 16, 2019

The use of α1-antitrypsin (αAT) for the treatment of steroid-refractory graft- versus-host disease (SR GvHD) has been previously shown to be an effective and safe therapeutic regimen. 1The loss of αAT through fecal matter has been associated with the presence of gastrointestinal (GI) GvHD. 2

On 27 March 2019, at the  45 th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Dr. Livia Giannoni, from Hôpital Saint-Louis, Paris, FR, presented a retrospective analysis from consecutive patients (n = 16; median age = 50 years; range, 18–56) receiving αAT for the treatment of GI SR GvHD over a 19 month period (September 2016–March 2018) following hematopoietic stem cell transplantation (HSCT). 3

Patients and methods:

  • Eligible patients:
    • Refractory to standard front-line therapy consisting of > 1 mg/kg/day of methyl prednisolone
    • Received ≥ 1 front-line therapies for SR GvHD
    • Received pre-treatment with H1-antihistamines
  • Patients received a loading dose of αAT (90 mg/kg; day 1), followed by seven maintenance doses of αAT (30 mg/kg; days 3, 5, 7, 9, 11, 13, and 15)
  • Total number of αAT courses: 18
  • Measures assessed as study outputs:
    • Weekly response assessments
    • Serum and fecal αAT, cytokine profiles, and T cell subsets assessed pre- and post-treatment

Key findings:


  • Median follow-up time: 440 days (range, 84–602)
  • Patients receiving ≥ 1 lines of immunosuppressive treatments for GvHD, other than steroids: 67%
  • Median time from HSCT to αAT therapy: 104 days (38–215)
  • Median time from onset of GvHD to initiation of αAT treatment: 65 days (12–198)
  • Median time from time of previous treatment to initiation of αAT therapy: 35 days (14–162)
  • Patients with grade III-IV GvHD: 72%
  • Serum albumin levels were severely decreased when measured prior to HSCT compared to during αAT treatment: 41.47 ± 2.90 vs24.35 ± 4.71
  • Overall response rate (ORR): 44%
  • Responses were lower in patients who:
    • Received ≥ 3 lines of prior treatment
    • Received treatment with ATG
    • Had multi-organ involvement
  • Complete remission (CR) rate: 27%
  • Median time to best response: 21 days (6–26)
  • At day 56, continued ORR: 39%
  • GI ORR: 61%
  • Median overall survival (OS) rate: 138 days
  • One-year OS rate: 48% (95% CI, 26–74)
  • Levels of serum αAT increased significantly, compared to baseline, during and after treatment, respectively: 1.72 g/L ± 0.46 vs2.22 g/L ± 0.48 vs2.5 g/L ± 0.64
  • Independent of patient response status, a decrease in circulating T regs following αAT therapy was seen ( P= 0.002)


  • No infusion-related reactions occurred
  • Common infectious events occurring between days 0–56 include: CMV reactivation (33%) and bloodstream infections (28%)
  • αAT therapeutic protocol was a concomitant cause of death in two patients

Dr. Giannoni concluded that for patients with high-risk GI SR GvHD, αAT has been demonstrated as an effective and safe therapeutic regimen, allowing for its potential use in the therapeutic landscape of SR GvHD. Moreover, the role of αAT as a pre-emptive therapeutic regimen in patients with SR GvHD is being examined in a prospective study ( NCT03459040) which will allow further validation of this therapy for the treatment of GI SR GvHD.

  1. Marcondes A.M. et al. Response of steroid-refractory acute GvHD to α1-antitrypsin. Biol Blood Marrow Transplant. 2016 Sep; 22(9): 1596–1601. DOI: 10.1016/j.bbmt.2016.05.011[Epub 2016 May 17].
  2. Magenau J.M. et al.α1-antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood. 2018 Mar 22; 131(12): 1372–1379. DOI: 10.1182/blood-2017-11-815746[Epub 2018 Feb 2].
  3. Giannoni L. et al. Human-derived α1-antirypsin is effective in a cohort of high-risk patients with steroid-resistant gastrointestinal graft-versus-host disease. 2019 Mar 27; OS10-5: 45 th Annual Meeting of the European Society for Blood and Marrow Transplantation, Frankfurt, DE.