CEC Count Changes to Support GvHD Diagnosis.

NCT02064972 | Completed DMC

• 1 other identifier: NP 1574
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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 may represent a marker of endothelial damage, we want to evaluate the changes in CEC counts of patients affected by hematological disorders undergoing allo-HSCT, as a function of endothelial damage. We will enroll 50 patients affected by hematologic disorders undergoing allo-HSCT. Peripheral blood will be drawn before (T1, baseline) and at the end of the conditioning regimen (T2, pre-transplant), upon confirmation of hematopoietic recovery (T3, engraftment) and thereafter at onset of GVHD (GVHD T4) and one week after the start of steroid therapy (T5, post-GvHD). All patients will also be checked for CEC at day + 28. CEC enumeration will be performed by using the CellSearch® System and a flowcytometry procedure. Through the conduct of this study, we expect to confirm our preliminary results on a larger series of patients, and to evaluate the predictive role of CEC on the occurrence of GvHD and prognostic response to treatment of GvHD. The possibility of early identification of patients who do not respond to traditional treatments of GvHD, and for this reason at a higher risk of morbidity and mortality, may allow greater individualization of the therapeutic program, for example with the introduction as early as possible of alternative treatments. In addition, the identification of patients at higher risk of non-responsiveness to steroid treatment, would allow, through a closer monitoring, the early introduction of additional treatment before the development of resistance/refractoriness to treatment of GvHD. The present study takes the form of a prospective study. The primary endpoint is the identification and enumeration of CECs in peripheral blood of patients with hematological disorder undergoing allo-HSCT, as a function of endothelial damage. The secondary endpoint is to define the prognostic and predictive value of the changes of CEC counts on the diagnosis of GvHD and response to treatment.

Conditions

Graft vs Host Disease; Complications of Organ Transplant Stem Cells; Endothelial Dysfunction

Keywords

Graft vs Host Disease; Hematopoietic Stem Cell Transplant; Biological Marker; Circulating Endothelial Cells; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (1)

• Changes from baseline (Timepoint 1) in Circulating Endothelial Cell (CEC) count at GvHD onset (Timepoint 4)

  CEC count changes will be evaluated between baseline and time of GvHD onset, within day + 100 post-transplant. In our preliminary series of 40 patients GvHD have manifested at a median of 27 days post-transplant (range 15-103).

  Basal (Timepoint 1) versus GvHD onset (Timepoint 4)

Secondary Outcomes (3)

• Changes from baseline (Timepoint 1) in Circulating Endothelial Cell (CEC) count at time of transplant (Timepoint 2)

  Basal (Timepoint 1) versus pre-transplant (Timepoint 2)

• Changes from baseline (Timepoint 1) in Circulating Endothelial Cell (CEC) count at time of engraftment (Timepoint 3).

  Basal (Timepoint 1) versus engraftment (Timepoint 3)

• Changes from GvHD onset (Timepoint 3) in Circulating Endothelial Cell (CEC) count at one week after the start of steroid therapy (Timepoint 5).

  GvHD onset (Timepoint 3) versus one week after the start of steroid therapy (Timepoint 5)

Study Arms (1)

Patients undergoing allo-HSCT, who manifest GvHD.

Patients undergoing allo-HSCT, that manifest GvHD. Patients undergoing allo-HSCT will have CEC count performed at the following timepoints: T1 (baseline), T2 (pre-transplant), T3 (engraftment), T4 (GvHD onset) and T5 (post-GvHD). All patients will also be checked for CEC at day + 28.

Other: Patients undergoing allo-HSCT, who manifest GvHD.

Interventions

Patients undergoing allo-HSCT, who manifest GvHD. OTHER

Changes in CEC counts in relation to GvHD ONSET

Patients undergoing allo-HSCT, who manifest GvHD.

Eligibility Criteria

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

Study Population

Patients, affected by hematologic disorders, undergoing allo-HSCT.

You may qualify if:

• Patients with hematological disorders undergoing allo-HSCT,
• Age 18-65 years.
• Sign of written informed consent form at the time of study entry.

You may not qualify if:

• No candidates to allo-HSCT.
• Patients under the age of 18 years.

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead
• Janssen Diagnostics, LLC: collaborator

Study Sites (1)

A.O. Spedali Civili of Brecia

Brescia, 25123, Italy

Location

Related Publications (10)

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  PMID: 17226859 BACKGROUND

• Woywodt A, Scheer J, Hambach L, Buchholz S, Ganser A, Haller H, Hertenstein B, Haubitz M. Circulating endothelial cells as a marker of endothelial damage in allogeneic hematopoietic stem cell transplantation. Blood. 2004 May 1;103(9):3603-5. doi: 10.1182/blood-2003-10-3479. Epub 2004 Jan 8.

  PMID: 14715625 BACKGROUND

• Damani S, Bacconi A, Libiger O, Chourasia AH, Serry R, Gollapudi R, Goldberg R, Rapeport K, Haaser S, Topol S, Knowlton S, Bethel K, Kuhn P, Wood M, Carragher B, Schork NJ, Jiang J, Rao C, Connelly M, Fowler VM, Topol EJ. Characterization of circulating endothelial cells in acute myocardial infarction. Sci Transl Med. 2012 Mar 21;4(126):126ra33. doi: 10.1126/scitranslmed.3003451.

  PMID: 22440735 BACKGROUND

• Chen YB, Cutler CS. Biomarkers for acute GVHD: can we predict the unpredictable? Bone Marrow Transplant. 2013 Jun;48(6):755-60. doi: 10.1038/bmt.2012.143. Epub 2012 Aug 6.

  PMID: 22863728 BACKGROUND

• Carreras E, Diaz-Ricart M. The role of the endothelium in the short-term complications of hematopoietic SCT. Bone Marrow Transplant. 2011 Dec;46(12):1495-502. doi: 10.1038/bmt.2011.65. Epub 2011 Apr 4.

  PMID: 21460864 BACKGROUND

• 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

• 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

• 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

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Camillo Almici, M.D.

  Transfusion Medicine, Spedali Civili Brescia, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 17, 2014
• Study Start: April 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 29, 2019

Record last verified: 2019-05

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)