Background: SMIs have improved outcomes in lymphoma/CLL. There is paucity of information about the safety and efficacy of alloSCT following SMIs. Methods: Data from 49 pts who received alloSCT between 2013-2018 at MDA and who have been previously treated with SMIs were retrospectively analyzed. Results: Histologies included CLL (n=31, 63%), mantle cell lymphoma (MCL) (n= 13, 27%), and follicular lymphoma (n= 5, 10%). Prior SMIs included ibrutinib [(n=46; 94%); 57% as ≥ 3rd line of therapy], venetoclax [(n=19, 39%); 68% as ≥ 3^rd line of therapy], idelalisib (n=6, 12%). Ibrutinib was discontinued prior alloSCT in 31(67%) pts. due to refractoriness (n=25), or intolerance (n=6). Seven of 19 (37%) pts had venetoclax discontinued to due refractoriness (n=6) or intolerance (n=1). Risk factors for CLL pts at alloSCT included a prior Richter’s (n=14, 45%), unmutated IGHV (15/23, 65%), presence of del17p (n=23; 74%), and complex cytogenetics (n=15; 48%). In addition, 18/20 (90%) CLL pts had abnormal mutations: most frequent were TP53 (n=14; 78%), BTK (n=6; 33%), SF3B1 (n=4; 22%) and 8/18 (44%) pts had > 2 mutations. Risk factors for MCL pts included: Ki67≥ 30 % (n=10/12, 83%), blastoid histology (n=6, 46%). Median age was 51 years, and 9 (18%) pts had a HCT-CI >4. Median prior lines of therapies was 4. Median duration of SMI therapy was 4.6 months. At transplant 40 (82%) pts had sensitive and 9 (18%) had refractory disease. Conditioning was nonmyeloablative (BFR or FCR) in 62%, RIC in 20% and myeloablative in 18%. Most pts (61%) received matched unrelated or matched sibling donors (22%); 8 (16%) had an alternative donor. The median follow-up for survivors was 12.4 months (range, 1-41.6). OS and PFS at 1 year were 77% and 68%, respectively. The CI of acute grade 2-4 and 3-4 GVHD were 33% and 7%, respectively. CI of 1-year chronic GVHD was 19%. Disease refractoriness and acute 3-4 GVHD were predicators for inferior OS and PFS by MV analysis. Similar survival results were observed in pts with or without mutations. Fourteen pts died due to progression (n=9), infection (n=2), acute (n=2) or chronic GVHD (n=1). Conclusions: AlloSCT is an effective therapy in pts with lymphoma/CLL pretreated with SMI. Our results suggest that alloSCT can overcome high-risk mutations associated with exposure to SMIs. Prospective confirmation in a larger # of pts is needed.