Faculty Collaboration Database

Complement-mediated thrombotic microangiopathy as a link between endothelial damage and steroid-refractory GVHD. Blood Adv 2018 Oct 23;2(20):2619-2628

Date

10/18/2018

Pubmed ID

30327370

Pubmed Central ID

PMC6199668

DOI

10.1182/bloodadvances.2018020321

Scopus ID

2-s2.0-85072254595 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA), a complication of hematopoietic cell transplant (HCT), is associated with significant morbidity and mortality. The pathophysiology and overlap of TA-TMA with other posttransplant complications such as graft-versus-host disease (GVHD) is poorly understood. We retrospectively identified cases of TA-TMA among patients with grade 3/4 gastrointestinal (GI) GVHD, reviewed intestinal biopsy specimens, and performed correlative testing of biomarkers associated with TA-TMA. TA-TMA was more common in patients with steroid-refractory GVHD compared with steroid-responsive GVHD (79.3% vs 42.1%; P = .001). Among patients surviving 100 days post-HCT, 1-year survival from day 100 was significantly better for patients who had not developed TA-TMA in the first 100 days (69.5% vs 36.7%; P < .001). Only 1 of 7 proposed TA-TMA histology criteria (mucosal hemorrhage) differed significantly based on GVHD steroid response. In multivariable modeling, steroid-refractory GVHD was a risk factor for development of TA-TMA (hazard ratio, 3.09; 95% confidence interval, 1.68-5.67; P < .001). There were no differences in complement activation at GVHD onset; however, 2 to 6 weeks later, patients with TA-TMA had higher levels of BBPlus and C5b-9, markers of alternative and terminal pathway activation (BBPlus: median, 600 vs 209.3 ng/mL; P = .0045) (C5b-9: median, 425.9 vs 258.4 ng/mL; P = .029). TA-TMA is associated with poor overall survival (OS) following HCT and may be detected early by histologic findings and may be differentiated from GVHD by measurement of alternative and terminal complement pathway activation. It is unknown whether treatment of TA-TMA will improve survival in steroid-refractory GVHD.

Author List

Wall SA, Zhao Q, Yearsley M, Blower L, Agyeman A, Ranganathan P, Yang S, Wu H, Bostic M, Jaglowski S, Brammer JE, William B, Choe H, Mims AS, Penza S, Efebera Y, Devine S, Cataland S, Davies SM, Vasu S

Author

Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Endothelium
Female
Graft vs Host Disease
Humans
Male
Middle Aged
Thrombotic Microangiopathies
Young Adult