Origin of CEC in Patients After Allo-HSCT

Endothelial Dysfunction Clinical Trial

— DCEC-PIANO  

Official title:

Search of Circulating Endothelial Cells of Donor Origin After Allogeneic Hematopoietic Stem Cell Transplantation: Evaluation for Potential Clinically Relevant Implications in the Context of Graft-Versus-Host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04038827
• Other study ID #: 0037975
• Status: Completed
• Start date: August 27, 2019
• Est. completion date: April 30, 2020

Study information

• Verified date: July 2020
• Source: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

We believe that CEC, besides coming from cells shedding from patient vasculature, could partly belong to donor, originating from the cellular graft.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 30, 2020
• Est. primary completion date: January 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Disease
• Endothelial Dysfunction
• Graft Versus Host Disease, Acute
• Graft vs Host Disease
• Immune Tolerance

Intervention

Diagnostic Test:
• D-CEC counting
By means of preliminary bulk separation step with the CellSearch system, single CEC will be sorted

Locations

Country	Name	City	State
Italy	ASST Spedali Civili di Brescia	Brescia

Sponsors (3)

Lead Sponsor	Collaborator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Università degli Studi di Brescia, University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (13)

Almici C, Neva A, Skert C, Bruno B, Verardi R, Di Palma A, Bianchetti A, Braga S, Piovani G, Cancelli V, Omedè P, Baeten K, Rotta G, Russo D, Marini M. Counting circulating endothelial cells in allo-HSCT: an ad hoc designed polychromatic flowcytometry-based panel versus the CellSearch System. Sci Rep. 2019 Jan 14;9(1):87. doi: 10.1038/s41598-018-36442-9. — View Citation

Almici C, Skert C, Bruno B, Bianchetti A, Verardi R, Di Palma A, Neva A, Braga S, Piccinelli G, Piovani G, Malagola M, Bernardi S, Giaccone L, Brunello L, Festuccia M, Baeten K, Russo D, Marini M. Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 2017 Dec;52(12):1637-1642. doi: 10.1038/bmt.2017.194. Epub 2017 Sep 11. — View Citation

Almici C, Skert C, Verardi R, Di Palma A, Bianchetti A, Neva A, Braga S, Malagola M, Turra A, Marini M, Russo D. Changes in circulating endothelial cells count could become a valuable tool in the diagnostic definition of acute graft-versus-host disease. Transplantation. 2014 Oct 15;98(7):706-12. doi: 10.1097/TP.0000000000000385. — View Citation

Cortesini R, Suciu-Foca N. ILT3+ ILT4+ tolerogenic endothelial cells in transplantation. Transplantation. 2006 Jul 15;82(1 Suppl):S30-2. — View Citation

Fadini GP, Avogaro A. Cell-based methods for ex vivo evaluation of human endothelial biology. Cardiovasc Res. 2010 Jul 1;87(1):12-21. doi: 10.1093/cvr/cvq119. Epub 2010 Apr 28. Review. — View Citation

Lanuti P, Rotta G, Almici C, Avvisati G, Budillon A, Doretto P, Malara N, Marini M, Neva A, Simeone P, Di Gennaro E, Leone A, Falda A, Tozzoli R, Gregorj C, Di Cerbo M, Trunzo V, Mollace V, Marchisio M, Miscia S. Endothelial progenitor cells, defined by the simultaneous surface expression of VEGFR2 and CD133, are not detectable in healthy peripheral and cord blood. Cytometry A. 2016 Mar;89(3):259-70. doi: 10.1002/cyto.a.22730. Epub 2015 Aug 25. — View Citation

Lanuti P, Simeone P, Rotta G, Almici C, Avvisati G, Azzaro R, Bologna G, Budillon A, Di Cerbo M, Di Gennaro E, Di Martino ML, Diodato A, Doretto P, Ercolino E, Falda A, Gregorj C, Leone A, Losa F, Malara N, Marini M, Mastroroberto P, Mollace V, Morelli M, Muggianu E, Musolino G, Neva A, Pierdomenico L, Pinna S, Piovani G, Roca MS, Russo D, Scotti L, Tirindelli MC, Trunzo V, Venturella R, Vitagliano C, Zullo F, Marchisio M, Miscia S. A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges. Sci Rep. 2018 Apr 11;8(1):5823. doi: 10.1038/s41598-018-24234-0. — View Citation

Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000 Jan;105(1):71-7. — View Citation

Penack O, Socié G, van den Brink MR. The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation. Blood. 2011 Apr 21;117(16):4181-9. doi: 10.1182/blood-2010-10-312934. Epub 2011 Jan 21. — View Citation

Pober JS. Is host endothelium a silver lining for allografts? Lancet. 2001 Jan 6;357(9249):2-3. — View Citation

Riesner K, Shi Y, Jacobi A, Kräter M, Kalupa M, McGearey A, Mertlitz S, Cordes S, Schrezenmeier JF, Mengwasser J, Westphal S, Perez-Hernandez D, Schmitt C, Dittmar G, Guck J, Penack O. Initiation of acute graft-versus-host disease by angiogenesis. Blood. 2017 Apr 6;129(14):2021-2032. doi: 10.1182/blood-2016-08-736314. Epub 2017 Jan 17. — View Citation

Taflin C, Charron D, Glotz D, Mooney N. Regulation of the CD4+ T cell allo-immune response by endothelial cells. Hum Immunol. 2012 Dec;73(12):1269-74. doi: 10.1016/j.humimm.2012.07.009. Epub 2012 Jul 16. Review. — View Citation

Wu SR, Reddy P. Tissue tolerance: a distinct concept to control acute GVHD severity. Blood. 2017 Mar 30;129(13):1747-1752. doi: 10.1182/blood-2016-09-740431. Epub 2017 Feb 2. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of D-CEC at time of engraftment in patients undergoing allo-HSCT	Single CEC will be isolated and STR profile determined	Within 30 days from allo-HSCT
Primary	Correlate presence/absence of D-CEC with GVHD manifestations	D-CEC presence will be correlated with GVHD onset	day +100 post allo-HSCT
Secondary	Presence of donor CEC embedded in the endothelial layer of patients microvasculature at late timepoint after allo-HSCT	CISH analysis will be performed on tissue biopsies at 3 months post-transplant	day +100 post allo-HSCT