Abstract

Chronic graft-versus-host disease (cGVHD) is the leading cause of mortality following allogeneic hematopoietic stem cell transplantation, also contributing to morbidity and worse quality of life. This study aimed to collect evidence on overall survival (OS) and non-relapse mortality (NRM) among cGVHD patients. A systematic review of English-language publications was conducted using PubMed. Search was limited to studies using the National Institute of Health Consensus Criteria for the diagnosis of cGVHD, published between 2007 and 2017, and studied human subjects with a cohort size of ≥100 patients. Thirty-eight studies were included. From the onset of cGVHD, the 1 and 2 year NRM rates ranged from 10% to 26%, and 10% to 32%, respectively. The 1 and 2 year OS rates from the onset of cGVHD ranged from 66% to 75%, and 59% to 81%, respectively. Patients with cGVHD had better OS (range of hazard ratio [RoHR]: 0.09 - 0.38), but increased NRM (RoHR: 2.4 - 4.8) compared to patients without cGVHD. Studies found that improved OS was primarily due to differences in relapse rate (RR). Higher cGVHD severity was reported to be associated with worse NRM (severe vs. mild/moderate, RoHR: 3.04 - 3.07). Four studies found a significant association between OS and cGVHD severity and 3 indicated better OS in case of lower cGVHD severity. Evidence suggests that the improved OS in cGVHD patients is due to lower risk of relapse, which can be explained with the presence of a potent graft-versus-tumor effect. However, NRM was found to be higher in patients with cGVHD and studies indicated an increased risk in the presence of more severe disease. A delicate balance is thought to exist between cGVHD severity as a source of NRM and a favorable effect on decreased RR in the presence of less severe cGVHD.

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