After allogeneic stem cell transplantation (alloSCT), patient-derived stem cells that survived the pre-transplant conditioning compete with engrafting donor stem cells for bone marrow (BM) repopulation. In addition, donor-derived alloreactive T-cells present in the stem cell product may favor establishment of complete donor-derived hematopoiesis by eliminating patient-derived lymphohematopoietic cells. T-cell depleted alloSCT with sequential transfer of potentially alloreactive T-cells by donor lymphocyte infusions (DLIs) provides a unique opportunity to selectively study how competitive repopulation and allo-immunological pressure influence the lymphohematopoietic recovery.
To determine the relative contribution of competitive repopulation and donor-derived anti-recipient allo-immunological pressure on the establishment of lymphohematopoietic chimerism after alloSCT.
In a retrospective cohort study of 281 acute leukemia patients treated according to a protocol combining alemtuzumab-based T-cell depleted alloSCT with prophylactic DLI, we investigated engraftment and quantitative donor chimerism in the BM and immune cell subsets. DLI-induced increase of chimerism and development of Graft-versus-Host-Disease (GvHD) were analyzed as complementary indicators for donor-derived anti-recipient allo-immunological pressure.
Profound suppression of patient immune cells by conditioning sufficed for sustained engraftment without necessity for myeloablative conditioning or development of clinically significant GvHD. While 61% of the patients without any DLI or GvHD showed full donor chimerism (FDC) in the BM at 6 months after alloSCT, only 24% showed FDC in the CD4+ T-cell compartment. In contrast, 75% of the patients who had received a DLI and 83% of the patients with clinically significant GvHD had FDC in this compartment. 72% of the patients with mixed hematopoiesis receiving DLI converted to complete donor-derived hematopoiesis, of whom only 34% developed clinically significant GvHD.
We show that competitive repopulation can be sufficient to reach complete donor-derived hematopoiesis, but that some allo-immunological pressure is needed for the establishment of a completely donor-derived T-cell compartment, either by the development of GvHD or by administration of DLI. We illustrate that it is possible to separate GvL from GvHD, as conversion to durable complete donor-derived hematopoiesis following DLI did not require induction of clinically significant GvHD.

Copyright © 2022. Published by Elsevier Inc.