Background: Allogeneic stem-cell transplantation (SCT) is curative therapy in AML by providing intensive chemotherapy and enhancing a graft-versus-leukemia (GVL) effect. The GVL effect is usually closely associated with GVHD. The use of haploidentical SCT (haploSCT) is rapidly increasing due to the introduction of non-T depleted methods, in particular with post-transplant cyclophosphamide (PTCy), with similar outcomes as following other donor sources. There is no data whether GVL after haploSCT is associated with GVHD as it is in matched donor SCT.
Methods: We assessed the impact of acute and chronic GVHD on SCT outcomes following non-T depleted haploSCT with PTCy, by using a series of landmark analyses.
Results: The study included 605 patients with AML in CR1 (73%) or CR2 (27%) after haploSCT with PTCy, given during the years 2009-2016. The median age was 53 years (range, 18-76). The overall rate of acute GVHD grade II-IV and III-IV was 28.4% and 8.0%, respectively. The rates of chronic GVHD of all grades and extensive were 32.7% and 12.3%, respectively. The 2-year leukemia-free survival (LFS) was 59.9%. 509 patients were alive and leukemia-free 100 days after SCT; 366 had no prior acute GVHD at this landmark, 107 had acute GVHD grade II and 36 had grade III-IV. The subsequent relapse rate was 20.3%, 18.3% and 11.9%, respectively (P=0.60). The subsequent non-relapse mortality (NRM) rate was 10.3%, 19.0% and 35.7%, respectively (P<0.001). LFS was 69.4%, 62.6% and 52.4%, respectively (P=0.01). Multivariate analysis showed that acute GVHD grade II was not associated with subsequent relapse (Hazard ratio (HR) 1.02, P=0.93), had borderline association with NRM (HR 1.79, P=0.09) and no association with LFS (HR 1.28, P=0.27). Acute GVHD grade III-IV was not associated with subsequent relapse (HR 0.92, P=0.87), but was associated with higher NRM (HR 5.23, P<0.001) and lower LFS (HR 2.35, P=0.003). 393 patients were alive and leukemia-free 6 months after SCT; 316 had no prior chronic GVHD, 55 had limited and 22 extensive chronic GVHD. The subsequent relapse rate was 14.3%, 9.2% and 23.9%, respectively (P=0.60). The subsequent NRM rate was 7.3%, 10.4% and 31.7%, respectively (P=0.003). LFS rate was 78.4%, 80.4% and 44.4%, respectively (P=0.01). Multivariate analysis showed that limited grade chronic GVHD was not associated with subsequent relapse (HR 0.69, P=0.44), NRM (HR 1.43, P=0.55) or LFS (HR 0.88, P=0.74). Extensive chronic GVHD was not associated with subsequent relapse (HR 1.44, P=0.56) but was associated with higher NRM (HR 5.77, P=0.004) and lower LFS (HR 2.75, P=0.01).
Conclusions: Acute and chronic GVHD of any grade were not associated with subsequent relapse. Acute GVHD grade III-IV and extensive chronic GVHD were associated with higher NRM and lower LFS. GVL is thus not closely associated with GVHD after non T-depleted haploSCT with PTCy. Future novel strategies for prevention of significant GVHD are warranted.
Disclosure: Nothing to declare