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Graft-Versus-Host Disease

IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD

Bone Marrow Transplantation volume 48, pages 722–728 (2013)Cite this article

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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.

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Acknowledgements

The authors would like to thank the patients for participating in research that could not benefit them but only future patients. This study could not happen without the dedication of Polly Louie, Lynne Fisk, Judy Wu, Glennis Doiron, Feng Zhou, Monja Metcalf, as well as the staff of the Alberta Blood and Marrow Transplant Program, including inpatient and outpatient nurses (lead by Lorraine Harrison, Joanne Leavitt and Naree Ager), and physicians, including Drs Nancy Zacarias, Ping Yue, Nizar Bahlis, Chris Brown, Peter Duggan, Michelle Geddes, Lynn Savoie, Mona Shafey, Loree Larratt, and Robert Turner. This work was funded by Genzyme/Sanofi (JS, JAR, DR and AG), Alberta Heritage Foundation for Medical Research, Canada Research Chair Program and Alberta Cancer Foundation.

Author contributions: LMP performed the ELISA assays and wrote the manuscript. YL established the ELISA assays and supervised their conduct. AUT and MHP reviewed charts for patient outcomes. PJP measured ATG levels. AWL facilitated determinations of γ-glutamyl transpeptidase, urea, total protein and cholinesterase. TSW lead statistical analyses. JAR, AG and DR critically reviewed the manuscript. JS designed the study, supervised its conduct and extensively edited the manuscript.

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Authors and Affiliations

  1. Department of Medicine, University of Calgary, Calgary, Alberta, Canada

    L M Pratt, Y Liu, A Ugarte-Torres, M Hoegh-Petersen, P J Podgorny, A W Lyon, T S Williamson, F M Khan, D A Stewart & J Storek

  2. Alberta Health Services, Calgary, Calgary, Alberta, Canada

    A Ugarte-Torres, A W Lyon, F M Khan, M A Chaudhry, A Daly, D A Stewart, J A Russell & J Storek

  3. Royal Melbourne Hospital, Parkville, Victoria, Australia

    A Grigg & D Ritchie

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Correspondence to J Storek.

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Pratt, L., Liu, Y., Ugarte-Torres, A. et al. IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD. Bone Marrow Transplant 48, 722–728 (2013). https://doi.org/10.1038/bmt.2012.210

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