Biomarker profiling of steroid-resistant acute GVHD in patients after infusion of mesenchymal stromal cells

L. C.J. Te Boome, C. Mansilla, L. E. Van Der Wagen, C. A. Lindemans, E. J. Petersen, E. Spierings, K. A. Thus, K. Westinga, M. Plantinga, M. Bierings, A. E.C. Broers, M. L.H. Cuijpers, G. W. Van Imhoff, J. J. Janssen, C. Huisman, S. Zeerleder, G. Huls, J. J. Boelens, N. M. Wulffraat, I. C.M. Slaper-CortenbachJ. Kuball

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57 Citaten (Scopus)

Samenvatting

We performed a prospective phase II study to evaluate clinical safety and outcome in 48 patients with steroid-refractory grade II-IV acute graft-versus-host disease (aGVHD) treated with mesenchymal stromal cells (MSCs). Clinical outcomes were correlated to comprehensive analyses of soluble and cellular biomarkers. Complete resolution (CR) of aGVHD at day 28 (CR-28) occurred in 12 (25%) patients, CR lasting >1 month (CR-B) occurred in 24 (50%) patients. One-year overall survival was significantly improved in CR-28 (75 versus 33%, P=0.020) and CR-B (79 versus 8%, P<0.001) versus non-CR patients. A six soluble biomarker-panel was predictive for mortality (HR 2.924; CI 1.485-5.758) when measured before MSC-administration. Suppression of tumorigenicity 2 (ST2) was only predictive for mortality 2 weeks after but not before MSC-administration (HR 2.389; CI 1.144-4.989). In addition, an increase in immature myeloid dendritic cells associated with decreased mortality (HR 0.554, CI 0.389-0.790). Patients had persisting T-cell responses against defined virus- and leukemia-associated antigens. In conclusion, our data emphasize the need to carefully assess biomarkers in cohorts with homogeneous GVHD treatments. Biomarkers might become an additional valuable component of composite end points for the rapid and efficient testing of novel compounds to decrease lifecycle of clinical testing and improve the success rate of phase II/III trials.

Originele taal-2Engels
Pagina's (van-tot)1839-1846
Aantal pagina's8
TijdschriftLeukemia
Volume29
Nummer van het tijdschrift9
DOI's
StatusGepubliceerd - 4 sep. 2015
Extern gepubliceerdJa

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