The Role of Donor Selection for a Second Allogeneic Stem Cell Transplantation in Patients with AML Relapsing after a First Transplant; A Study on Behalf of the Acute Leukemia Working Party of EBMT

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. Methods and Results. The study included 556 patients with AML relapsing after a first allogeneic SCT (SCT1) given in CR1 from an HLA-matched sibling (sib, n= 294) or a matched unrelated donor (MUD, 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 (44%) and 309 had active leukemia (55%) at the time of SCT2. The conditioning regimen was myeloablative (MAC, 66%) or reduced-intensity (RIC, 34%) for SCT1, and 41% and 59%, respectively for SCT2. 19% of all patients had acute GVHD grade II-IV and 20% had chronic GVHD after SCT1 and before relapse. Patients were divided into 3 groups based on the donor selected for SCT2; 1) same donor (n=163, sib/sib-112, MUD/MUD-51), 2) different HLA-matched donor (n=305, sib/different sib-44, sib/MUD-93, MUD/ different MUD- 168), 3) haplo-donor (n=88, sib/haplo-45, MUD/haplo-43). All haploSCT were non T-depleted. There were some differences between the 3 groups in the timing of relapse and SCT2. The median time from SCT1 to relapse was similar; 10.6, 12.5 and 9.3 months, respectively (P=0.14). However, the median time from relapse to SCT2 was shorter for the same donor group; 2.8, 3.7 and 3.5 months, respectively (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. Prior chronic GVHD after SCT1 is associated with lower relapse rate after SCT2. The role of prior chronic GVHD in donor selection should be further investigated. Disclosures Finke: Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Gramatzki:Affimed: Research Funding. Stelljes:Novartis: Honoraria; Amgen: Honoraria; JAZZ: Honoraria; MSD: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Stoelzel:Neovii: Speakers Bureau. Mohty:MaaT Pharma: Consultancy, Honoraria.