Risk Factors and Outcome of Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation—Results from a Single-Center Observational Study

Abstract

Chronic graft versus host disease (cGVHD) is the most frequent long-term complication after allogeneic stem cell transplantation (allo-SCT) and results in impaired quality of life and increased long-term morbidity and mortality. We analyzed 243 patients with cGVHD, documented according to the 2005 revised National Institutes of Health consensus criteria, to identify risk factors for the occurrence of cGVHD and outcomes for the patients with cGVHD. Patients without evidence of cGVHD (n = 147) were used as controls. Performing univariate and multivariate Cox regression analyses, we identified prior acute GVHD grades III or IV (hazard ratio [HR], 2.01; P = .005), use of peripheral blood stem cell graft (HR, 2.10; P = .03), and HLA-mismatched allo-SCT from unrelated donor (HR, 1.57; P = .02) as independent risk factors for cGVHD. Performing Kaplan-Meier analyses, progressive compared with de novo and quiescent onset of cGVHD and a platelet count of less than 100/nL compared with more than 100/nL at the time of cGVHD onset were associated with a significantly increased cumulative incidence of transplantation-related mortality (TRM) and significantly decreased overall survival. Furthermore, we found a significantly higher incidence of TRM in patients with severe cGVHD compared with patients without cGVHD (58% versus 11%, P < .0001). However, in subgroup analysis, patients with severe cGVHD and involvement of the lung, liver, or gastrointestinal (GI) tract had a 6.5-fold significantly higher incidence of TRM (72%), whereas patients with severe cGVHD lacking lung, liver, or GI involvement had only a 2.8-fold significantly higher incidence of TRM (31%) compared with patients without cGVHD (11%; P < .0001 and P = .03). Patients without lung, liver, or GI involvement did not have a significantly different TRM compared with patients with moderate cGVHD (31% versus 25%, P = .52). In conclusion, we confirm prior known risk factors for the occurrence of cGVHD and subsequent mortality and we provide evidence that the presence of lung, liver, or GI involvement in patients with severe cGVHD defines a subgroup with high mortality after allo-SCT; however, in the absence of these risk factors, the outcome appears not to be impaired compared with moderate cGVHD.

Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

“…For female donor to male recipient transplantations, there was a trend towards a higher chance for moderate to severe cGVHD, but this did not reach statistical significance. We also did not find a role of previous aGVHD as a predictor for the development of moderate to severe cGVHD, as opposed to other studies [5,6]. A possible explanation may be early RR and TRM that occurred in the control group, resulting in a relatively high mortality rate within 6 months after transplantation.…”

“…AlloSCT is a standard treatment for patients with AML/ MDS with high risk of relapse [1][2][3]. Around 30-70% of transplanted patients who are treated with non-myeloablative conditioning and receive a T-repleted graft collected from peripheral blood develop chronic graft-versus-host disease [4][5][6]. Moderate to severe cGVHD is associated with high morbidity, hospital dependency and poor quality of life as compared to mild cGVHD [6,7].…”

“…Until now, multiple studies have identified risk factors associated with the development of cGVHD [5,11,12], but only a few studies have been carried out to identify risk factors associated with the severity of cGVHD [6,13]. Known risk factors associated with the development of cGVHD independently of the severity of cGVHD are: female donor to male recipient, HLA mismatch, peripheral blood as a source of stem cells, high numbers of infused T cells, recipient age, positive CMV serology and antecedent acute GVHD [5,11,12,14]. Risk factors which are published to be associated with the severity of cGVHD are: transplantation from an immuned female donor to a male recipient, antecedent of aGVHD, CML and NMA conditioning, but most of these factors were identified in the context of bone marrow used as graft source instead of peripheral blood.…”

Different risk factors of acute and chronic graft-versus-host disease with conventional prophylaxis and posttransplantation cyclophosphamide in matched related and unrelated donor transplantations

“…Th e risk factors identifi ed for moderate and severe chronic GVHD with conventional prophylaxis were similar to the ones previously reported [27,28]. Th e history of severe acute GVHD was the most predominant risk factor.…”

Establishing a standardized system for review and adjudication of chronic graft‐vs‐host disease data in accordance with the National Institutes Consensus criteria

“…The NIH further refined these guidelines in 2014 . In recent years, the prognostic value of the NIH consensus criteria (NCC) has been validated supporting the use of this new system . While most of Bone Marrow Transplant (BMT) centers have adopted these guidelines into their routine clinical assessments, GVHD evaluation requires laborious time‐consuming assessments and can lead to clinician inter‐variability in both diagnosis and scoring of GVHD.…”