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Published on: March 17, 2020
Predictors and outcomes of flares in chronic graft-versus-host disease
Najla El Jurdi1, Grigori Okoev2, Todd E DeFor3
1Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, USA. neljurdi@umn.edu.
Insights
Chronic graft-versus-host disease (cGVHD) flares are common after allogeneic hematopoietic cell transplantation (HCT), impacting immunosuppressive therapy (IST) duration. Flares may reduce relapse risk but do not worsen survival outcomes.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Chronic graft-versus-host disease (cGVHD) is a major complication following allogeneic hematopoietic cell transplantation (HCT).
- Prolonged immunosuppressive therapy (IST) is standard for cGVHD management, often involving slow tapering and posing risks of flares and treatment failure.
Purpose of the Study:
- To investigate the incidence, characteristics, and outcomes of cGVHD flares after HCT.
- To identify factors associated with cGVHD flare risk.
- To evaluate the impact of flares on IST duration, relapse, non-relapse mortality (NRM), and overall survival (OS).
Main Methods:
- Retrospective analysis of 145 adult HCT recipients diagnosed with cGVHD between 2010 and 2018.
- Estimation of 2-year cumulative incidence and time-to-first flare.
- Analysis of flare treatment, associated risk factors, and impact on clinical outcomes.
Main Results:
- The 2-year cumulative incidence of cGVHD flares was 60%, with a median time to first flare of 188 days.
- Quiescent cGVHD at onset was associated with a higher flare risk (HR 1.8).
- Patients experiencing flares required longer IST and had lower rates of durable IST discontinuation (31% vs. 86%).
- Flares showed a protective effect on relapse (HR 0.2) but did not worsen NRM or OS.
Conclusions:
- cGVHD flares are frequent and associated with prolonged IST duration.
- While flares may offer a protective effect against relapse, they necessitate improved management strategies to mitigate IST-related morbidity.
- Identifying patients at risk for flares is crucial for optimizing cGVHD treatment and long-term outcomes.
Abstract:
Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) requires prolonged immunosuppressive therapy (IST), often requiring slow tapering with patients experiencing cGVHD flares and treatment failure. In 145 adult recipients developing cGVHD after matched sibling or umbilical cord blood donor HCT from 2010 to 2018, 2-year cumulative incidence of flares after cGVHD diagnosis was estimated at 60% (95% CI, 51-70%), with median time-to-first flare of 188 days (range, 16-751). Of 88 patients experiencing a flare, 32 (36%) had multiple flares (range, 2-4). First flare treatment consisted of an increase in prednisone dose in 77 patients (88%), plus topical therapy in 8 (9%) or another systemic IST in 43 patients (49%). Higher flare risk was associated with quiescent type of cGVHD at onset (HR 1.8; 95% CI: 1.1-2.7; p = 0.04). Patients without a flare required a shorter duration of IST and were more likely to achieve a durable discontinuation of systemic IST (86% vs. 31% for ≥6 consecutive months). Flares were associated with protective effect on relapse (HR 0.2, 95% CI: 0.1-0.3), however not with worsened 2-year NRM or OS. Flares of cGVHD identify a group needing better approaches to limit the duration of IST and thus the morbidity of cGVHD.
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