Chronic Graft vs. Host Disease (cGVHD) Hinders Long-Term Functional Recovery after Hematopoietic Cell Transplantation.
Authors: Wong F. Lennie , Francisco Liton , Forman Stephen J. , Gonzales Mitzi , Sabado Melanie , Hanby Cara , Grant Marcia , Bhatia Smita 
Published: October 2019

Abstract
The growing number of long-term HCT survivors has created the need to identify factors that could play a critical role in the survivors’ reintegration into daily life, which in turn would inform the quality of life (QOL) of the survivors. Using a longitudinal study design, we administered the City of Hope-QOL instrument to evaluate the four domains of QOL (physical, psychological, social, and spiritual well-being), as well as fatigue, anxiety, distress, and return to full-time work in a large cohort of patients undergoing HCT at City of Hope. The outcomes were evaluated before transplantation, at 6m, 1y, 2y, and 3y. Longitudinal trends for these outcomes were evaluated using the Generalized Estimating Equation method, adjusting for potential confounders such as age, race, BMI, disease. Our cohort included 313 adults (median age at HCT 48y; 56% males) undergoing autologous (n=181) or allogeneic (n=132) HCT for hematologic malignancies or severe aplastic anemia; 111 patients (65.3% of eligible) completed 3y follow-up so far. Overall, the mean scores for psychological, social, and spiritual well-being improved significantly over time compared to pre-HCT levels (p<.05); that for physical well-being did not demonstrate a significant change from the pre-HCT levels. Although HCT survivors in general appeared to recover well, we identified subgroups that faced long-term limitations. Notably, longitudinal trends of mean scores for all four QOL domains were significantly worse (p<.05) for allogeneic HCT recipients with cGVHD compared to allogeneic HCT recipients without cGVHD or autologous HCT recipients (Figure); the latter two groups were statistically indistinguishable for all domains of QOL. Moreover, physical and spiritual well-being of patients with cGVHD continued to decline with time, while that of allogeneic recipients without cGVHD or autologous HCT recipients improved or remained unchanged with time after HCT. All patients combined, anxiety, fatigue, distress improved significantly after 6m to 1y after HCT compared to the pre-HCT time-point. However, patients with cGVHD reported higher levels of anxiety, fatigue (Figure), and distress when compared to those without cGVHD. The prevalence of the most fatigued patients (worst 20th percentile of fatigue score) decreased from 39% before transplant to 26% at 3y (p=.02). However, during the post-HCT time points, the prevalence was two-fold higher for allogeneic recipients with cGVHD compared to allogeneic recipients without cGVHD or autologous HCT recipients (p<.005). About 25% of patients reported returning to full-time work at 6m, which increased to 58% at 3y (p<.0001). Multivariate analysis showed that females, those older than 50 years, and those with higher levels of fatigue were less likely to return to full-time work. This study demonstrates that at 3y after HCT 25% of patients are significantly fatigued and over 40% do not return to full-time work, and that patients with cGVHD represent a vulnerable subgroup, requiring effective, multidisciplinary interventions.
Figure Figure