Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Full donor chimerism was reported three times in the absence of myelosuppressive regimen, only after liver or multivisceral transplantation, but never after kidney transplantation. Recent data supported the presence in intestinal mucosa and liver of hematopoietic stem and progenitor cells (HSPC), endowed with multilineage differentiation potential both in vitro and in vivo.
*Methods: We here report the case of a child with end-stage renal disease and a severe primary immune deficiency (Schimke immuno-osseous dysplasia), who developed a life-threatening GvHD after an isolated kidney transplantation. Monoclonal HLA class I allele-specific antibodies were used to discriminate HLA-A23+ donor and HLA-A2+ recipient cells, in combination with a pan-HLA class I antibody. Donor (KMR045) and recipient (KMR047)-specific single nucleotide polymorphisms were also quantified in blood and bone marrow cells using quantitative polymerase chain reaction.
*Results: After a complete remission of GvHD had been obtained, donor chimerism remained unexpectedly high, over 99% and 96% in total blood and T cells, respectively. Moreover, the red blood type changed to the donor type, as evidenced by the switch from the C+ to C- Rhesus antigen, while a full and durable donor chimerism was observed in all other lymphoid (B and NK cells) and myeloid (monocytes, neutrophils, platelets) lineages. Taken together, these findings strongly suggested that donor-derived HSPC had engrafted into the host and were able to support hematopoiesis. A bone marrow aspiration was performed on day 156 post-transplant. Donor chimerism was measured at roughly 96% in magnetically-sorted CD34+ HSPC bone marrow cells with both quantitative PCR and flow cytometry. However, thorough flow cytometry analysis showed that donor chimerism greatly varied throughout the hematopoietic differentiation pathway. Although host-derived cells still accounted for 72% of the most immature hematopoietic stem cells (HSC) their contribution dropped to 42% in the downstream multipotent progenitors (MPP) and far less among more committed progenitors. In absence of myeloablative regimen, the conversion to full donor chimerism is thought to be driven by lympho-hematopoietic graft-vs-host reaction (GVHR), which makes space for the engraftment of donor HSPC. In the present case, the decreasing frequency of recipient cells along the differentiation pathway suggests that GVHR in the bone marrow actively repressed host progenitors-derived hematopoiesis, but spared host HSC residing in immune-privileged niches, in line with recent experimental data.
*Conclusions: This observation provides the first evidence of donor-derived HSPC engraftment and stable GVHR-driven chimerism after an isolated kidney transplantation.
To cite this abstract in AMA style:Zuber J, Boyer O, Neven B, Six E, Berthaud R, Rabah MOuld, Sobrino S, Lagresle C, André-Schmutz I, Cavazzana M, Blanche S, Salomon R. Full and Sustained Donor Hematopoietic Chimerism after an Isolated Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/full-and-sustained-donor-hematopoietic-chimerism-after-an-isolated-kidney-transplantation/. Accessed October 29, 2020.
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