Long-Term Survival and Quality of Life Assessment After Allogeneic Stem-Cell Transplantation; Comparable Results Following Myeloablative and Reduced-Intensity Conditioning,
Authors: Shimoni Avichai , Tallis Eran , Shem-Tov Noga , Volchek Yulia , Yerushalmi Ronit , Nagler Arnon 
Published: October 2019

Abstract
Abstract 4096
Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients (pts) with various hematological malignancies. SCT is associated with substantial mortality during the first 2 years after SCT whereas after 2 years survival curves often reach a plateau. However, late mortality and late events continue to cause treatment failures through the late post-transplant course. Quality of life (QoL) is increasingly recognized as an important long-term end-point. The pattern of late events and QoL has been reported following myeloablative conditioning (MAC) but is not well defined in the reduced-intensity (RIC) setting. To explore late outcomes we retrospectively analyzed SCT results in a cohort of 726 pts given allogeneic SCT between 1/2000 and 8/2009. Pts meeting standard eligibility criteria were given MAC (n=207) while pts considered at excessive risk for non-relapse mortality (NRM) were given fludarabine based RIC (n=385) or reduced-toxicity myeloablative conditioning (RTC, n=134). 246 pts were alive and disease-free 2 years after SCT. Their median age was 51 years (17–72). Diagnoses included AML/MDS (n=131), ALL (n=24), lymphatic diseases (n=48), CML/MPD (n=29), non-malignant (n=14). Donors were HLA-matched siblings (n=151), unrelated (n=91) or alternative donors (n=4). Conditioning was MAC (n=72), RIC (n=118) or RTC (n=56). At 2 years after SCT, 172 pts had a history of chronic GVHD, graded as moderate-severe (mod-sev) in 44% and 29% of pts after MAC and RIC/RTC, respectively (p=0.03). 68% and 43% of pts were still on immune suppressive therapy (IST) 2 years after SCT, respectively (p=0.001). With a median follow-up of 68 months after SCT (range, 25–140), the probability of pts surviving disease-free 2 years after SCT to remain alive and disease-free for the next 5 years was 84% (95CI, 75–93) and 82% (95CI, 75–89) after MAC and RIC/RTC, respectively (p=NS). There were 35 deaths beyond 2 years, 15 due to relapse and 20 due to NRM. NRM included 9 deaths due to second cancers; 2 due to relapse of a primary malignancy in pts transplanted for therapy related AML, 4 other solid tumors, 3 donor MDS/AML. 9 pts died of chGVHD/infections and 2 of myocardial infarction. In all, the cumulative incidence of late NRM was 7% (4–11), similar after MAC and RIC/RTC. However, more pts in the MAC group died of chGVHD/ infections (6.9% Vs 2.3%, p=0.08), while more pts in the RIC/RTC group died of second cancers (4.6% Vs 1.4%, p=NS). 24 pts relapsed, 25–102 months after SCT, cumulative incidence 11% (7–16); 9% after MAC and 11% after RIC/RTC (p=NS); 15 died, 9 are alive following further therapies. The kinetics of late relapses was similar with MAC and RIC/RTC. Advanced age (>55) and moderate-severe chGVHD were the most significant predicting factors for shortened survival. OS 5 years after the 2-year time-point was 77% and 89%, in the older and younger groups, respectively (p=0.05). OS was 78% and 90% in pts with and without mod-sev chGVHD, respectively (p=0.004). Multivariate analysis confirmed these as independent factors, HR 2.1 (p=0.07) and 2.6 (p=0.006), respectively. The conditioning regimen, disease type and status at SCT and donor type were not predictive. A history of mod-sev chGVHD predicted for NRM, HR 5.2 (p=0.001). Advanced disease status at SCT predicted for relapse risk, HR 2.6 (P=0.004). The cumulative probability of stopping IST by 8 years after MAC and RIC/RTC SCT was 59 and 75%, respectively (p=0.001). For patients who stopped IST the median duration of IST was 30 and 20 months, respectively (p=0.05). QoL was assessed by the EORTC QLQ-C30 questionnaire. Mean QOL score was 69, 66 and 65 after MAC, RIC and RTC, respectively. A low QOL score (20 points below median) was reported by 15%, 14% and 19%, respectively (p=NS). There was no difference in any of the other domains of QoL assessment as well. Multiple regression analysis identified continuous need IST and reporting depression as factors correlated with a low score while a healthy lifestyle (including return to work, physical and sexual activity) and academic education were associated with high score. In conclusion, the pattern of late outcome is similar after MAC and RIC/RTC. Late NRM is similar although chGVHD is less severe and the required duration of IST is shorter after RIC/RTC. This may lead to better QoL. Younger pts who are disease-free 2 years after SCT, particularly those with no mod-sev chGVHD can expect good long-term outcome and relatively good QOL.

Disclosures:
No relevant conflicts of interest to declare.