Early Mixed Chimerism and Relapse Rates for Acute Myeloid Leukemia/Myelodysplastic Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation

Despite advances in allogeneic stem cell transplant (alloHCT), relapse rates (RR) can reach 50% for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Many patients do not achieve full donor chimerism by day 28. Studies investigating the prognostic significance of early mixed chimerism (eMC) on RR have been inconsistent, with the largest study by Mossallam, et al reporting no correlation between RR and eMC. We retrospectively reviewed 181 AML and MDS patients who underwent alloHCT from January 1, 2021- August 21, 2023, at our institution. Patients were excluded if deceased before 30 days post-transplant. A binary logistic regression examined the effect of day 28 CD3 and CD33 chimerism for the whole cohort, each disease, and for endpoints of day 365 relapse free survival (RFS) and day 180 RR. Complete chimerism at day 28 was defined as ≥95% for CD3 and 100% donor for CD33 due to the small number of patients with CD33 chimerism of 95-99%. The median age of patients was 49 (20-78) years. 130 (72%) had AML and 38 (21%) had active disease at the time of transplant. The median HCT-CI was 2 (0-9) and 86 (48%) received myeloablative (MAC) conditioning. 83 (45%) patients had minimal residual disease (MRD) assessments pre HCT, with 37 (20%) MRD+ and 46 (25%) MRD-. Post HCT MRD was reported in 44 (24%) patients, with 16 (9%) MRD+ and 28 (15%) MRD-. Post-HCT maintenance was given to 43 (33%) patients and started at a median of 85 days (27-248) after transplant. 107 (60%) patients had CD3 eMC at day 28. Of these, 29 (27%) achieved full chimerism by day 84. Five (3%) patients had CD33 eMC at day 28 and none achieved full chimerism by day 84. All patients receiving MAC had complete CD33 chimerism while 58 (67%) had CD3 eMC at day 28. Complete CD33 chimerism was associated with reduced RR at day 180 (p=0.02). There was no difference in RFS at 1 year between patients with eMC and complete chimerism. There were no significant findings for the specific disease cohorts for relapse by day 180. Conditioning intensity, diagnosis, HCT-CI, stem cell source and donor type did not affect relapse. There was no difference in overall survival between patients with eMC and complete chimerism. The most common causes of death were relapse (n=36, 53%), infection (n=8, 12%) and GVHD (n=8, 12%). There was no difference in relapse rates in patients with CD3 eMC. The use of post-transplant maintenance in high-risk patients likely impacted our relapse rates. We also may not have seen the effect of CD3 eMC on relapse rates due to our small sample size. While CD33 eMC at day 28 was associated with relapse at day 180, there was a small number of patients in our cohort. Further studies with a larger patient population of eMC CD33 are needed before we can determine its impact on relapse.