Endothelial Dysfunction, Graft Versus Host Disease, Acute, Immune Tolerance
Conditions
Keywords
Circulating Endothelial Cells, Graft versus Host Disease, Neovascularization, Allotransplantation
Brief summary
We believe that CEC, besides coming from cells shedding from patient vasculature, could partly belong to donor, originating from the cellular graft.
Detailed description
In consideration of the fact that the vascular endothelium has been shown to be a target of GvHD in early stage and that the count of CEC represent a marker of endothelial damage, we want to correlate the presence of donor CEC at engraftment with a putative protective function against GVHD manifestations. We will enroll patients affected by hematologic disorders undergoing allo-HSCT. At time of engraftment and at + 3 months after allo-HSCT, CEC identified and counted by means of the CellSearch system, will be recovered from the counting cartridge and further sorted at the single cell level. STR profile of each single CEC recovered will be performed in order to define host versus donor origin of each CEC analysed. Through the conduct of this study, we expect to upfront identify patients who will or will not manifest GvHD. This result will allow definitely different clinical approaches: stringent monitoring and early therapeutic intervention, before refractory disease's development, in the formers, while, sparing unnecessarily expensive testing or heavier treatment in the latters.
Interventions
DIAGNOSTIC_TESTD-CEC counting
By means of preliminary bulk separation step with the CellSearch system, single CEC will be sorted
Sponsors
Università degli Studi di Brescia
University of Turin, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* patients undergoing allo-HSCT for their neoplastic hematologic diseases * written informed consent * achievement of hematopoietic recovery from aplasia post-allo-HSCT * predictable life expectancy \> 6 months
Exclusion criteria
* presence of active malignant hematologic disease at time of allo-HSCT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of D-CEC at time of engraftment in patients undergoing allo-HSCT | Within 30 days from allo-HSCT | Single CEC will be isolated and STR profile determined |
| Correlate presence/absence of D-CEC with GVHD manifestations | day +100 post allo-HSCT | D-CEC presence will be correlated with GVHD onset |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of donor CEC embedded in the endothelial layer of patients microvasculature at late timepoint after allo-HSCT | day +100 post allo-HSCT | CISH analysis will be performed on tissue biopsies at 3 months post-transplant |
Countries
Italy
Outcome results
None listed