Trends in Allogeneic Transplantation for Favorable Risk Acute Myeloid Leukemia in First Complete Remission: A Longitudinal Study of > 15 Years from the ALWP/EBMT

Background Allogeneic transplantation (HSCT) is usually not indicated in favorable risk AML at CR1due to transplant-related mortality. However, in recent years, HSCTs are with significantly lower mortality. Methods We assessed outcomes of HSCT in favorable risk AML (t (8:21), inv (16), and NPM1mutFLT3WT) in CR1, comparing 3 time periods: 2005-2009, 2010-2014, and 2015-2021. Results 1850 pts were included, 526 with t (8:21), 625 with inv (16), and 699 with NPM1mutFLT3WT (normal karyotype). 222 pts were transplanted in 2005-2009, 392 in 2010-2014, and 1236 in 2015-2021. As follow-ups differed, all survival events were censored at 3 y. Pts undergoing HSCT in 2015-2021 were older, with a median age of 50.9 (range 18.2-76.4) vs. 40.4 (range 18.3-67.7) and 42.4 (range 18.4-71) y, in those transplanted in 2005-2009 and 2010-2014 (p<0.0001). More pts ≥50 y of age were transplanted in the latest period with 52.7% vs. the 2 earlier periods 27.9% and 32.1% (p<0.0001) and figures for >60 y were 25.4% vs. 8.1% and 11% (p<0.0001). In 2005-2009 the frequent diagnosis was t (8:21) at 44.6%, while in 2015-2021, it was NPM1mutFLT3WT at 45.6% (p<0001). In 2005-2009, the frequent donors were siblings (63.1%), while in 2015-2021 they were unrelated (50.7%). Haploidentical transplants increased from 5.9% to 14.5% (p<0.0001). BM grafts decreased from 24.8% to 13.2%, while PB grafts increased from 75.2% to 86.8% (p<0.0001). Conditioning was myeloablative in 69.8%, 64.8%, and 60.2% and was RIC in 30.2%, 35.2%, and 39.8% in pts transplanted in 2005-2009, 2010-2014, and 2015-2021 (p=0.014). GVHD prophylaxis with in vivo T cell depletion or post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 compared to the other two periods (p<0.0001).Day 60 engraftment was 98.2 % vs. 98.4% vs. 98.5% (p=0.17). Incidence of acute (a) GVHD grade II-IV was 18.2%, 21.1%, and 21.6%; grade III-IV was 5.1%, 5.7%, and 7.3% while the incidence of 3-y chronic (c) GVHD was 49.3%, 50.4%, and 39.2%.On MVA the incidence of total cGVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005-2009, hazard ratio (HR) =0.74 (95% CI 0.56-0.99, p=0.046), and GRFS improved for pts transplanted from 2010-2014 vs. those transplanted in 2005-2009, HR=0.74 (95% CI 0.56-0.98, p=0.037) (Figure 1). All other HSCT outcome parameters did not differ (Figure 1) with no improvement ≥2015 vs.2010-2014 (Figure-1 A). LFS, OS, and GRFS were superior in pts with t (8:21) with HR=1.32 (95% CI 1.03-1.68, p=0.026), HR=1.38 (95% CI 1.04-1.83, p=0.027) and HR=01.25 (95% CI 1.02-1.53, p=0.035). Conclusions Analyzing pts with favorable risk AML in CR1, transplanted over 16 years, we observed an increased number of transplants in pts >60y, from unrelated and haplo donors with PB grafts and in vivo T cell depletion or PTCy as GVHD prophylaxis. Most importantly, 3-y GRFS improved ≥2010 and total cGVHD reduced ≥2015, while other HSCT outcome parameters have not changed.