Contributions
Abstract: PB2439
Type: Publication Only
Background
Chronic graft-versus-host disease (cGVHD) is a serious and life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) affecting 30% to 70% of patients. It is characterized by systemic inflammation and fibrosis with a heterogeneous presentations affecting a wide range of tissues and organs. cGVHD is the leading cause of non-relapse mortality (NRM) following HSCT, also contributing to morbidity and a decrease in quality of life.
Aims
To perform a systematic literature review of evidence (1) on overall survival (OS) and NRM among cGVHD patients and (2) on the effect of cGVHD on OS and NRM compared to patients without cGVHD.
Methods
A systematic review of English-language articles was conducted in PubMed. Literature search was limited to studies that applied the National Institute of Health (NIH) Consensus Criteria for the diagnosis and staging of cGVHD, published between 2007 and 2017, studied human subjects with a cohort size of at least 100 patients. Included studies were assessed for quality with a NIH quality assessment tool. NRM and OS values measured among cGVHD patients were extracted from the articles. In the evaluation of cGVHD-effect on OR and NRM we extracted data only from those analyses that applied a multivariate study design.
Results
From the screened 1682 publications, 38 studies were included. From the onset of cGVHD, the 1 and 2 year NRM rates ranged from 10% to 26%, and from 10% to 32%, respectively. The 1 and 2 year OS rates from the onset of cGVHD ranged from 66% to 75% and from 59% to 81%, respectively. Studies found that 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 where cGVHD was included as a time-dependent covariate in the multivariate analysis found that the improved OS was primarily due to differences in relapse rate (RR). These results showed that patients with cGVHD had significantly lower RR than patients without cGVHD: no cGVHD vs. classic cGVHD, HR: 0.46; and no cGVHD vs. mild / moderate / severe cGVHD, RoHR: 0.12 - 0.26. However, higher NRM was observed in several sub-groups of cGVHD patients when they were compared to those without cGVHD: cGVHD after acute GVHD, HR: 4.83; de novo cGVHD, HR: 3.52; classic cGVHD, HR: 2.4; and overlap cGVHD, HR: 2.5. Furthermore, 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. Overlap GVHD was associated with worse OS (HR: 2.1) and higher NRM (HR: 2.8) compared with classic cGVHD.
Conclusion
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 (GVT) 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. Considering the importance of the GVT effect and higher risk of NRM associated with more severe disease, there exists an unmet medical need for novel approaches to ameliorate the severity of cGVHD whilst preserving the benefits of the GVT effect.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Chronic graft-versus-host, Mortality, Survival, Systematic review
Abstract: PB2439
Type: Publication Only
Background
Chronic graft-versus-host disease (cGVHD) is a serious and life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) affecting 30% to 70% of patients. It is characterized by systemic inflammation and fibrosis with a heterogeneous presentations affecting a wide range of tissues and organs. cGVHD is the leading cause of non-relapse mortality (NRM) following HSCT, also contributing to morbidity and a decrease in quality of life.
Aims
To perform a systematic literature review of evidence (1) on overall survival (OS) and NRM among cGVHD patients and (2) on the effect of cGVHD on OS and NRM compared to patients without cGVHD.
Methods
A systematic review of English-language articles was conducted in PubMed. Literature search was limited to studies that applied the National Institute of Health (NIH) Consensus Criteria for the diagnosis and staging of cGVHD, published between 2007 and 2017, studied human subjects with a cohort size of at least 100 patients. Included studies were assessed for quality with a NIH quality assessment tool. NRM and OS values measured among cGVHD patients were extracted from the articles. In the evaluation of cGVHD-effect on OR and NRM we extracted data only from those analyses that applied a multivariate study design.
Results
From the screened 1682 publications, 38 studies were included. From the onset of cGVHD, the 1 and 2 year NRM rates ranged from 10% to 26%, and from 10% to 32%, respectively. The 1 and 2 year OS rates from the onset of cGVHD ranged from 66% to 75% and from 59% to 81%, respectively. Studies found that 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 where cGVHD was included as a time-dependent covariate in the multivariate analysis found that the improved OS was primarily due to differences in relapse rate (RR). These results showed that patients with cGVHD had significantly lower RR than patients without cGVHD: no cGVHD vs. classic cGVHD, HR: 0.46; and no cGVHD vs. mild / moderate / severe cGVHD, RoHR: 0.12 - 0.26. However, higher NRM was observed in several sub-groups of cGVHD patients when they were compared to those without cGVHD: cGVHD after acute GVHD, HR: 4.83; de novo cGVHD, HR: 3.52; classic cGVHD, HR: 2.4; and overlap cGVHD, HR: 2.5. Furthermore, 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. Overlap GVHD was associated with worse OS (HR: 2.1) and higher NRM (HR: 2.8) compared with classic cGVHD.
Conclusion
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 (GVT) 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. Considering the importance of the GVT effect and higher risk of NRM associated with more severe disease, there exists an unmet medical need for novel approaches to ameliorate the severity of cGVHD whilst preserving the benefits of the GVT effect.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Chronic graft-versus-host, Mortality, Survival, Systematic review