CT-368 Discordance of Chimerism in the Blood and Bone Marrow as a Possible Sign of Adverse Outcome After Allo-HSCT

Abstract

DNA isolated from bone marrow (BM) or peripheral blood (PB) of patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) is used to assess hematopoietic chimerism. Both sources are presumably equivalent for this purpose. Here, we report several allo-HSTC cases with BM chimerism not matching that of PB and vice versa. To investigate the possible association between the disparity of chimerism in paired PB and BM samples and disease features in post-transplant acute myeloid leukemia patients. This study analyzed the STR profiles in the DNA of paired archival BM and PB samples of 43 patients who received allo-HSCT in the National Medical Research Center for Hematology (Moscow, Russia) from 2016 to 2022. Paired BM and PB samples were collected with a time difference of one day or less. Chimerism was assessed by STR-PCR. STR profiles were evaluated by PCR with a COrDIS Plus multiplex kit (Gordiz Ltd, Russia). Patients with mixed hematopoietic chimerism at certain time points during monitoring were included. In 8 patients out of 43 (18.6%), a disparity of chimerism between PB and BM samples was found. In 3 patients (7%) in the early stages after allo-HSCT, chimerism measured in the PB sample was ≥2 times higher than in BM. In 5 (11.6%) patients, the proportion of recipient DNA in BM was twice as high as in PB. In 2 patients, this phenomenon might be due to donor lymphocytes transfusion before measuring chimerism. For 3 patients, no simple explanation for this phenomenon is evident so far. However, all 5 relapsed. Four patients died from the progression of the disease, and 1 underwent a second transplant and maintains remission. The predominance of recipient DNA in PB samples compared to BM, noted in the early stages after allo-HSCT, may not correspond to the real picture due to delayed hematopoietic reconstitution. The study of chimerism in sorted cell populations might provide an explanation for host predominance in BM over PB. Probably, such patients relapsing in the early stages after allo-HSCT could have chimerism split between certain cell lineages. Further studies of chimerism in paired PB and BM samples on extended cohorts of post-transplant patients are required.