The Impact of Age on Quality of Life, Functional Status, and Overall Survival in Patients with Moderate-Severe Chronic Graft-Versus-Host Disease

Introduction:  Chronic graft-versus –host disease (GVHD) causes a significant reduction in patients’ quality of life (QOL) and functional status.  Although older patients undergoing allogeneic stem cell transplantation may experience higher morbidity, it is not known if moderate to severe chronic GVHD has a worse impact on QOL or survival outcomes for older patients. 

Methods:  We utilized data of patients with moderate or severe chronic GVHD (N=522, 1661 follow-up visits, a total of 2,183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort.  We examined the relationship between age group (adolescent and young adult “AYA” 18-40, “middle-aged” 41-59, and “older” ≥ 60 years) and patient-reported outcomes, functional status, non-relapse mortality and overall survival in patients with moderate-severe chronic GVHD.  Patient-reported outcomes included (1) QOL as measured by Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT)  (2) chronic GVHD symptom burden as measured by the Lee Symptom Scale; and (3) physical fitness as measured by the Human Activity Profile (HAP).  Functional status was assessed using the 2-minute walk test (2MWT).  Because of multiple testing, p-values <0.01 were considered significant.

Results:  This study included 115 (22%) AYA, 279 (53%) middle-aged and 128 (25%) older patients with moderate (58%) or severe (42%) chronic GVHD.  Older patients (≥60) were similar to younger patients in gender, comorbidity score, time from transplant, prior acute GVHD, severity of chronic GVHD, but differed in disease distribution and conditioning regimen intensity.  Despite more physical limitations in older patients as measured by worse functional status [shorter 2MWT (p=0.002)], and lower HAP scores (p=0.001)] than AYA and middle-aged patients, older patients had better QOL [FACT-BMT (p=0.01)] scores compared to middle-aged patients and similar to AYA patients.  Older patients reported less psychological symptoms (Lee Psychological Scale (p<0.001), and better emotional functioning [FACT-Emotional Well-being (p=0.001)] than AYA and middle-aged patients.  In multivariable linear mixed models adjusted for clinical covariates, older patients had better QOL (FACT-BMT) than middle-aged patients (estimate 5.7, P=0.004) and comparable to AYA patients (estimate -0.04, p=0.99).  Non-relapse mortality and overall survival were similar between the age groups in unadjusted analyses and after adjusting for clinical covariates.

Conclusion:  Older patients with moderate or severe chronic GVHD have preserved QOL and similar overall survival and non-relapse mortality when compared to younger patients despite higher physical and functional limitations.  Our findings suggest that moderate or severe chronic GVHD does not have a disproportionate effect on QOL or survival in older patients.