Role of the Microparticles and of Tissue Factor in the Pro-thrombotic Phenotype and the Thromboembolic Complications During the Acute Lymphoblastic Leukemia in Children. (THROMBLEUKEMIA)

Role of the Microparticles and of Tissue Factor in the Pro-thrombotic Phenotype and the Thromboembolic Complications During the Acute Lymphoblastic Leukemia in Children

Acute lymphoblastic leukemia is the most common malignancy of the child. Current therapeutic strategies allow healing of over 80% of children. However these treatments are associated with toxicity, with a mortality of 1-2%. The most frequent complications, occuring during treatment initiation, are the thromboembolic complications.

The most commonly accepted explanation is that of an anti-thrombin depletion by chemotherapy used in the treatment, L-asparaginase. But the anti-thrombin supplementation showed no efficacy in the prevention of these thromboembolic complications. Therefore most authors consider that a multifactorial mechanism is behind these events, involving both treatment and malignant cells. The interaction of these two factors participate in the damage of the vascular endothelium.

The microparticles are membrane fragments derived from budding from the membrane of activated cells or apoptosis. Their thrombogenic role is linked to the expression of coagulation activators such as tissue factor. It is also associated with their role in the modulation of signaling pathways involved in the invasiveness and angiogenesis in endothelial cells.

In acute lymphoblastic leukemia, the presence and role of microparticles have not been studied. Our hypothesis is that of production of microparticles upon lysis of blasts then upon activation of endothelial cells induced by the induction therapy, participating in a procoagulant phenotype.

Study Overview

• Status: Completed
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: Blood sample

Detailed Description

The aims of this study are

• quantify the microparticles in children receiving induction therapy for Acute lymphoblastic leukemia at diagnosis and during treatment
• study the origin of these particles and the expression and activity of the tissue factor on their surface, at diagnosis and during treatment

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Reims, France, 51092
    • CHU de Reims

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children with acute lymphoblastic leukemia
• children and their parents consenting to participate to the study
• children enrolled in the national healthcare insurance program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: children with acute lymphoblastic leukemia	Other: Blood sample; Blood sample to quantify microparticles and to study expression and activity of the tissue factor on their surface

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of microparticules	Presence of microparticles investigated using flow cytometry	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of microparticules	Presence of microparticles investigated using flow cytometry	Day 8
Presence of microparticules	Presence of microparticles investigated using flow cytometry	Day 15
Presence of microparticules	Presence of microparticles investigated using flow cytometry	Day 25
Presence of microparticules	Presence of microparticles investigated using flow cytometry	Day 36
expression of the tissue factor	expression of the tissue factor investigated using flow cytometry	Day 0
expression of the tissue factor	expression of the tissue factor investigated using flow cytometry	Day 3
expression of the tissue factor	expression of the tissue factor investigated using flow cytometry	Day 15
expression of the tissue factor	expression of the tissue factor investigated using flow cytometry	Day 25
expression of the tissue factor	expression of the tissue factor investigated using flow cytometry	Day 36
Thromboembolic complication	complication thromboembolic diagnosed by the clinical examination and by the imaging	Day 36

Collaborators and Investigators

• Sponsor: CHU de Reims

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): March 21, 2017
• Study Completion (Actual): March 21, 2017

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: PA13047