EBMT 2019 | Endothelial Activation and Stress Index (EASIX)  to predict outcome after allogeneic hematopoietic cell transplantation (allo-HCT)

Despite its curative potential, allo-HCT is still hampered by a high non-relapse mortality (NRM) and the risk for severe acute GvHD. Methods to predict and eventually prevent these complications are warranted.

On 25 March 2019, Oral Session 1 (OS2) took place at the 45th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE. During this session, Miriam Sanchez-Escamilla, from the IDIVAL (Research Institute of Marques de Valdecilla), presented validated results of the prognostic value of the Endothelial Activation and Stress Index (EASIX), in adult patients undergoing unmodified or CD34-selected allo-HCT.

The objective of this study was to assess the validity of the EASIX score to predict non-relapse mortality (NRM), acute GvHD and overall survival (OS) during allo-HCT.

Study design

  • N = 509 adult patients
  • N = 152, unmodified RIC or non-myeloablative (NMA) allo-HCT
  • N = 364, CD34-selected myeloablative conditioning (MAC)
  • Median age: 55.6 years (19.6–78.7)
  • Male (59%)
  • Female (41%)
  • Majority of patients had myeloid malignancies (72%)
  • Primary endpoint of the study was overall survival (OS)
  • EASIX score was calculated based on standard laboratory parameters (LDH*Creatinine/platelet counts) and was assessed at several time-points before and after allo-HCT:
  • Before (pre EASIX), at day 30 (EASIX d30), day 100 (EASIX d100) and onset of aGvHD (EASIXaGvHD)

Key results

  • Median follow-up: 4.8 years (0.7-10) among survivors
  • 1- and 3-year OS were: 79.9% (95% CI, 76.2-83.2) and 63.2% (95% CI, 5.7–67.3), respectively

 

Predicting OS

 

Univariant analysis

HR (95% CI)

P  value

Pre-EASIX

1.17 (1.02–1.35)

0.022

EASIX d30

1.54 (1.37–1.74)

<0.001

EASIX d100

1.52 (1.34–1.72)

<0.001

EASIX-aGvHD

1.27 (1.09–1.48)

0.003

Table 1: EASIX predicts lower OS

  • The 1- and 3-year NRM were 13.2% (95% CI, 10.4–16.3) and 22.2% (95% CI, 18.6–25.9), respectively

 

Predicting NRM

 

Univariant analysis

HR (95% CI)

P  value

Pre-EASIX

1.05 (0.94–1.18)

0.394

EASIX d30

1.33 (1.20–1.47)

<0.001

EASIX d100

1.36 (1.23–1.51)

<0.001

EASIX-aGvHD

1.16 (1.01–1.33)

0.032

Table 2: EASIX predicts lower NRM

  • One year cumulative incidence of grade I–IV, II–IV, and III–IV aGvHD was 44.4% (95% CI, 40.0–48.7), 33.0% (95% CI, 29.0–37.1) and 10.4% (95% CI, 8.0–13.3), respectively

 

Predicting grades of aGvHD

 

 

 

Grade

HR (95% CI)

 

P  value

Pre-EASIX

I–IV

II–IV

III–IV

1.09 (0.98–1.21)

1.07 (0.95–1.21)

1.23 (1.01–1.50)

0.106 

0.257 

0.044

Table 3: Pre-EASIX predicts grade III-IV aGvHD

  • Causes of death in 211 patients, at last, follow up included:
  • Relapse (34%)
  • GvHD (25%)
  • Infection (20%)

Conclusion

Dr. Sanchez-Escamilla concluded that a higher EASIX scores at day 30, day 100, and at the onset of aGvHD are associated with higher NRM and inferior OS with a more prominent association in patients receiving unmodified allo-HCT compared to patients receiving CD34-selected allo-HCT. Furthermore, a high EASIX score before allo-HCT predicted high-grade acute GvHD.

The study identified that endothelial damage is a significant contributor to poorer outcomes after allo-HCT. The study validated that the EASIX formula delivers an easy complimentary tool to predict outcomes in these patients.

References

Sanchez-Escamilla. M. et al. Endothelial Activation and Stress Index results in unmodified and CD34-selected grafts. Abstract OS1-2: 45th EBMT Annual Meeting, Frankfurt, Germany

Luft T. et al. EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. The Lancet Haematology. 2017 Sep 1;4(9):e414-23. DOI:10.1016/S2352-3026(17)30108-4

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