Impact of Chronic Graft-versus-Host Disease on Late Relapse and Survival on 7,489 Patients after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Leukemia

Abstract

Purpose Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active. Experimental design The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT. Results Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.

Risk factors for relapse after allogeneic transplantation in acute myeloid leukemia

“…15,16 Chronic GvHD reduced the chance of relapse in many studies; however, in a recent registry study of the Center for International Blood and Marrow Transplant Research (CIBMTR), its impact seemed only clinically relevant for CML after myeloablative alloSCT and not for AML. 17 In this study, cGvHD was primarily associated with a higher transplant-related mortality (TRM).…”

Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells

“…Recent studies have shown that the quality of life of patients with cGVHD is much poorer, with a higher frequency of cardiovascular disease, metabolic syndrome, diabetes mellitus, obesity, cognitive issues, fatigue, sexual dysfunction, and endocrine abnormalities. [1][2][3][4] Biomarkers that can act as diagnostic, prognostic, and predictive markers for cGVHD are needed to improve the ability to treat cGVHD effectively. Criteria for such biomarkers are well defined in the recent National Institutes of Health (NIH) Chronic GVHD consensus report.…”

Prevalence and determinants of fatigue in patients with moderate to severe chronic GvHD

“…5,6 Chronic GvHD is also associated with a graft-versus-tumor effect and a lower rate of malignant relapse. 7,8 Organ complications secondary to cGvHD and immunosuppressive medications contribute to the substantial impact on morbidity.…”