Origin of CEC in Patients After Allo-HSCT

NCT ID: NCT04038827

Last Updated: 2020-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

15 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-08-27

Study Completion Date

2020-04-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Graft Versus Host Disease, Acute Endothelial Dysfunction Immune Tolerance

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Interventions

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D-CEC counting

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Università degli Studi di Brescia

OTHER

Sponsor Role collaborator

University of Turin, Italy

OTHER

Sponsor Role collaborator

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role lead

Responsible Party

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Camillo Almici MD

Director of the Stem Cells Lab

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Camillo Almici, MD

Role: PRINCIPAL_INVESTIGATOR

ASST Spedali Civili di Brescia

Locations

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ASST Spedali Civili di Brescia

Brescia, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
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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.

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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.

Reference Type BACKGROUND
PMID: 26305912 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29643468 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25119132 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28892085 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30643152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16829792 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22813652 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11197355 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28153825 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10619863 (View on PubMed)

Other Identifiers

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0037975

Identifier Type: -

Identifier Source: org_study_id

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