Origin of CEC in Patients After Allo-HSCT

NCT04038827 | Completed

• 1 other identifier: 0037975
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Graft Versus Host Disease, Acute; Endothelial Dysfunction; Immune Tolerance

Keywords

Circulating Endothelial Cells; Graft versus Host Disease; Neovascularization; Allotransplantation

Outcome Measures

Primary Outcomes (2)

• 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

• Correlate presence/absence of D-CEC with GVHD manifestations

  D-CEC presence will be correlated with GVHD onset

  day +100 post allo-HSCT

Secondary Outcomes (1)

• Presence of donor CEC embedded in the endothelial layer of patients microvasculature at late timepoint after allo-HSCT

  day +100 post allo-HSCT

Interventions

D-CEC counting DIAGNOSTIC_TEST

By means of preliminary bulk separation step with the CellSearch system, single CEC will be sorted

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing allo-HSCT for their neoplastic hematologic disorders

You may qualify if:

• 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

You may not qualify if:

• presence of active malignant hematologic disease at time of allo-HSCT

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead
• Università degli Studi di Brescia: collaborator
• University of Turin, Italy: collaborator

Study Sites (1)

ASST Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Related Publications (13)

• Penack O, Socie 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.

  PMID: 21258010 BACKGROUND

• Riesner K, Shi Y, Jacobi A, Krater 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.

  PMID: 28096092 BACKGROUND

• 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.

  PMID: 20427336 BACKGROUND

• 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.

  PMID: 26305912 BACKGROUND

• 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.

  PMID: 29643468 BACKGROUND

• 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.

  PMID: 25119132 BACKGROUND

• 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.

  PMID: 28892085 BACKGROUND

• Almici C, Neva A, Skert C, Bruno B, Verardi R, Di Palma A, Bianchetti A, Braga S, Piovani G, Cancelli V, Omede 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.

  PMID: 30643152 BACKGROUND

• Cortesini R, Suciu-Foca N. ILT3+ ILT4+ tolerogenic endothelial cells in transplantation. Transplantation. 2006 Jul 15;82(1 Suppl):S30-2. doi: 10.1097/01.tp.0000231437.12890.64.

  PMID: 16829792 BACKGROUND

• 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.

  PMID: 22813652 BACKGROUND

• Pober JS. Is host endothelium a silver lining for allografts? Lancet. 2001 Jan 6;357(9249):2-3. doi: 10.1016/S0140-6736(00)03558-3. No abstract available.

  PMID: 11197355 BACKGROUND

• 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.

  PMID: 28153825 BACKGROUND

• 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. doi: 10.1172/JCI8071.

  PMID: 10619863 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

DNA will be obtained from each single CEC

MeSH Terms

Conditions

Graft vs Host Disease; Neovascularization, Pathologic

Condition Hierarchy (Ancestors)

Immune System Diseases; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Camillo Almici, MD

  ASST Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Stem Cells Lab

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 31, 2019
• Study Start: August 27, 2019
• Primary Completion: January 31, 2020
• Study Completion: April 30, 2020
• Last Updated: July 8, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: after publication of results
• Access Criteria: Request to Principal Investigator

Locations

IT (1)