PF754 PERMANENT IMPAIRMENT‐FREE, RELAPSE‐FREE SURVIVAL: A NOVEL COMPOSITE ENDPOINT TO EVALUATE LONG‐TERM SUCCESS IN ALLOGENEIC STEM CELL TRANSPLANTATION
Authors: Y. Adachi, K. Ozeki, S. Ukai, K. Sagou, N. Fukushima, A. Kohno
Journal: HemaSphere (2019)

Background: Permanent impairment of vital organs is one of transplant‐related health problems affecting quality of life and morbidity even in patients who did not develop graft‐versus‐host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo‐HCT), but no data are available on permanent impairment of multiple organs. Aims: Our aims were to evaluate long‐term trasplant success by estimating the cumulative incidence of permanent impairment and the probability of survival after allo‐HCT without permanent impairment, relapse or death, which we called permanent impairment‐free, relapse‐free survival (PIRFS). Methods: We estimated cumulative incidence of permanent impairment of six vital organs and a novel composite endpoint of PIRFS in a retrospective study including 164 recipients of first allo‐HCT in Konan Kosei Hospital. The vital organs whose function was assessed in this study were the heart, lungs, liver, digestive tracts, kidneys, and central nerve system. We used “The American Medical Association's Guides to the Evaluation of Permanent Impairment” to assess the degree of permanent impairment on the same scale in the different organs. We defined permanent impairment as over 26–30% impairment of the whole person in six organs by using whole person impairment rating. Persistence of impairment for more than 6 months after the diagnosis of impairment was required in order to regard the impairment as permanent. The impairment in the first 6 months after allo‐HCT was excluded to avoid misclassifying reversible impairment as permanent. Results: The median follow‐up period for the surviving patients was 1846 days (range, 425–4055). Conventional GVHD‐free/relapse‐free survival (GRFS) at 5 years and PIRFS at 5 years were 33.8% (95% CI, 26.5%–41.3%) and 40.6% (95% CI, 32.6%–48.4%). PIRFS was higher than GRFS at any time after allo‐HCT in the whole cohort. However, in patients who underwent umbilical cord blood transplantation (UCBT), PIRFS became lower than GRFS after day 397 post‐transplant. In the UCBT recipients, the 5‐year GRFS and PIRFS were 47.6% (95% CI, 34.3%–59.7%) and 39.2% (95% CI, 26.6%–51.5%). The 5‐year cumulative incidence of permanent impairment was 20.9% (95% CI, 13.7%–29.0%) in the survivors for ≥180 days without relapse. Using multivariate analysis, we showed that high disease risk (HR, 1.91; 95% CI, 1.26–2.88; P &lt; 0.01) and KPS ≤90% at transplant (HR, 1.73; 95% CI, 1.14–2.63; P = 0.01) were significantly associated with the lower PIRFS. UCBT (HR, 2.35; 95% CI, 1.11–4.99; P = 0.03), acute GVHD grade 3–4 by day 180 (HR, 3.59; 95% CI, 1.04–12.4; P = 0.04) and thrombotic microangiopathy by day 180 (HR, 2.74; 95% CI, 1.10–6.87; P = 0.03) were significantly associated with the higher incidence of permanent impairment. Summary/Conclusion: Our study demonstrated that PIRFS represented healthy life for survivors after allo‐HCT and differed significantly based upon disease risk, KPS at transplant. The evaluation of PIRFS yields novel information regarding quality of long‐term survival after allo‐HCT, which cannot be represented even in well‐executed endpoints such as GRFS. Thus, we propose that PIRFS is a novel composite endpoint to evaluate long‐term transplant success in a different perspective from previous evaluation methods. image