Late acute graft-versus-host disease: A prospective analysis of clinical outcomes and circulating angiogenic factors

Shernan G. Holtan, Nandita Khera, John E. Levine, Xiaoyu Chai, Barry Storer, Hien D. Liu, Yoshihiro Inamoto, George L. Chen, Sebastian Mayer, Mukta Arora, Jeanne Palmer, Mary E D Flowers, Corey S. Cutler, Alexander Lukez, Sally Arai, Aleksandr Lazaryan, Laura Newell, Christa Krupski, Madan H. Jagasia, Iskra PusicWilliam Wood, Anne S. Renteria, Gregory Yanik, William J. Hogan, Elizabeth Hexner, Francis Ayuk, Ernst Holler, Phandee Watanaboonyongcharoen, Yvonne A. Efebera, James L M Ferrara, Angela Panoskaltsis Mortari, Daniel Weisdorf, Stephanie J. Lee, Joseph Pidala

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n 5 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n 5 55) and controls (n 5 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD.

Original languageEnglish (US)
Pages (from-to)2350-2358
Number of pages9
JournalBlood
Volume128
Issue number19
DOIs
StatePublished - Nov 10 2016

    Fingerprint

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Holtan, S. G., Khera, N., Levine, J. E., Chai, X., Storer, B., Liu, H. D., Inamoto, Y., Chen, G. L., Mayer, S., Arora, M., Palmer, J., Flowers, M. E. D., Cutler, C. S., Lukez, A., Arai, S., Lazaryan, A., Newell, L., Krupski, C., Jagasia, M. H., ... Pidala, J. (2016). Late acute graft-versus-host disease: A prospective analysis of clinical outcomes and circulating angiogenic factors. Blood, 128(19), 2350-2358. https://doi.org/10.1182/blood-2015-09-669846