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Published on: October 31, 2012
IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD
L M Pratt1, Y Liu, A Ugarte-Torres
1Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Insights
Low levels of interleukin-15 (IL15) on day 7 after allogeneic hematopoietic cell transplantation (HCT) predict the development of significant chronic graft-versus-host disease (cGVHD), guiding preemptive therapy.
Area of Science:
- Immunology
- Hematology
- Transplantation Medicine
Background:
- Chronic graft-versus-host disease (cGVHD) is a significant complication following allogeneic hematopoietic cell transplantation (HCT).
- Early intervention with preemptive therapy may improve outcomes for cGVHD.
- Identifying reliable biomarkers for early prediction of cGVHD is crucial.
Purpose of the Study:
- To investigate whether serum biomarker levels on day 7 or 28 post-HCT can predict the development of significant cGVHD.
- To identify potential biomarkers for early cGVHD risk stratification.
Main Methods:
- A discovery cohort of 153 HCT recipients conditioned with specific agents (BU, fludarabine, ATG) had serum biomarker levels measured.
- Serum levels of various cytokines and other markers, including IL15, were analyzed.
- A validation cohort of 105 HCT recipients confirmed the findings.
Main Results:
- Low serum levels of interleukin-15 (IL15) (<30.6 ng/L) on day 7 were significantly associated with an increased likelihood of developing significant cGVHD.
- This association was validated in a separate cohort, with low IL15 correlating to a 3.7-fold higher risk.
- Low IL15 levels were not linked to relapse but trended with acute GVHD and were associated with lower infection rates.
Conclusions:
- Serum IL15 levels on day 7 serve as a predictive biomarker for significant cGVHD following HCT.
- This finding can potentially guide the early administration of preemptive therapies for cGVHD.
Abstract:
Chronic GVHD (cGVHD) is an important complication of allogeneic hematopoietic cell transplantation (HCT). As preemptive therapy might be efficacious if administered early post transplant, we set out to determine whether cGVHD can be predicted from the serum level of a biomarker on day 7 or 28. In a discovery cohort of 153 HCT recipients conditioned with BU, fludarabine and rabbit antithymocyte globulin (ATG), we determined serum levels of B-cell-activating factor, vascular endothelial growth factor, soluble TNF-α receptor 1, soluble IL2 receptor α, IL5, IL6, IL7, IL15, γ-glutamyl transpeptidase, cholinesterase, total protein, urea and ATG. Patients with low levels of IL15 (<30.6 ng/L) on day 7 had 2.7-fold higher likelihood of developing significant cGVHD (needing systemic immunosuppressive therapy) than patients with higher IL15 levels (P<0.001). This was validated in a validation cohort of 105 similarly-treated patients; those with low IL15 levels had 3.7-fold higher likelihood of developing significant cGVHD (P=0.001). Low IL15 was not associated with relapse; it trended to be associated with acute GVHD and was associated with low infection rates. In conclusion, low IL15 levels on day 7 are predictive of cGVHD, and thus could be useful in guiding preemptive therapy.
