LAUSR

Introduction Recurrent disease is the major cause of treatment failure after allogeneic stem cell transplantation (SCT) in patients with AML. Second SCT (SCT2) is a valid treatment option in this setting but outcome is relatively poor. Haplo-identical (haplo) SCT is increasingly used over the last decade due to the introduction of non T-depleted methods. Prior studies have shown similar outcome when using the same or different HLA-matched donor for SCT2. However, there is relatively limited data on the use of haplo-donors in this setting. Methods and Results The study included 556 patients with AML relapsing after a first allogeneic SCT (SCT1) given in CR1 from sibling (sib, n= 294) or unrelated donor (UD, n=262) and given SCT2 during the years 2006-2016. The median age at SCT2 was 46 years (20-73). 247 patients were in CR2 (45%) and 309 had active leukemia (55%) at SCT2. The conditioning regimen for SCT1 was myeloablative (MAC, 66%) or reduced-intensity (RIC, 34%), and 41% and 59%, respectively for SCT2. Patients were divided into 3 groups based on the donor selected for SCT2; 1) same donor (n=163, sib/sib-112, UD/UD-51), 2) different matched donor (n=305, sib/different sib-44, sib/UD-93, UD/ different UD- 168), 3) haplo-donor (n=88, sib/haplo-45, UD/haplo-43). All haploSCT were non T-depleted. The 2-year leukemia-free survival (LFS) after SCT2 was 23.5%, 23.7% and 21.8%, respectively (unadjusted P=0.30). Multivariate analysis showed no effect of second donor type on subsequent relapse, hazard ratio (HR) 0.96 (P=0.83) and 1.20 (P=0.47) for different donor and haplo-donor compared to same donor, respectively. UD in SCT1, CR2 at SCT2 and chronic GVHD after SCT1 were associated with reduced relapse risk after SCT2, HR 0.70 (P=0.02), 0.60 (P=0.001) and 0.66 (P=0.03), respectively. Second donor type did predict for non-relapse mortality (NRM) after SCT2; HR 1.26 (P=0.41) and 2.18 (P=0.02) for different donor and haplo-donor compared to same donor, respectively. Advanced age and MAC in SCT1 also predicted for NRM, HR 1.40 (P Conclusions Second SCT with the same donor or different matched donor is associated with similar outcomes in patients with relapsed AML after a first SCT. However, SCT2 with a haplo-donor is associated with higher NRM and lower LFS, mostly in patients given MAC in SCT1. Second haplo donor does not provide better GVL effect in this setting.