Neutrophil Extracellular Traps (NETs) Formation Following Chemotherapy and Their Role in Antitumor Activity

Neutrophil Extracellular Traps (NETs) Formation Following Chemotherapy for Pediatric Hematological and Solid Tumors, and Its Relation to Other Neutrophil Functions and the Role of NETs in Antitumor Activity

Examine neutrophil extracellular traps (NETs) formation, in relation to other neutrophil functions like chemotaxis, superoxide production, hydrogen peroxide production, and the presence of myeloperoxidase, in pediatric patients undergoing chemotherpy for solid and hematological malignancies. This data could shed new light on the mechanism responsible for the increased susceptibility to infection among these patients and aid in improving their prophylactic antimicrobial treatment.

NETs formation against tumor cell lines and their ability to kill tumor cells will also be examined. The finding of NETs activity against tumor cells could have a major contribution to the investigators understanding of the function of the immune system against cancer.

Study Overview

• Status: Unknown
• Conditions: Pediatric Solid Malignancies; Pediatric Hematological Malignancies

Detailed Description

Neutrophil function, including NETs formation, chemotaxis, superoxide production, hydrogen peroxide production, and the presence of myeloperoxidase, will be examined in 50 pediatric patientsundergoing chemotherapy for solid and hematological malignancies. Children with the following malignancies will be examined: acute lymphoblastic leukemia,acute myelogenous leukemia,Hodgkin's lymphoma,non-Hodgkin's lymphoma, primary bone sarcoma,rhabdomyosarcoma,non-rhabdomyosarcoma,neuroblastoma,Wilms' tumor,hepatoblastoma or hepatocellular carcinoma,germ cell tumors, and hystiocytosis. Also those with brain tumors such as medulloblastom,low grade glioma,high grade glioma,ependymoma,and embryonal and pineal region tumors. Data gathered on the patients will include background data (age, gender, ethnicity) and background diseases, data on current illness (histologic type, grade, stage, response treatment,infectious episodes), and on the use of ranulocyte-colony stimulating factor (G-CSF).

The following time points will be examined:

1. At diagnosis, before initiation of chemotherapy.
2. immediately before the 2nd course.
3. After the middle course.
4. A month after the last course.
5. Three months after the last course.
6. In acute myelogenous leukemia and acute lymphoblastic leukemia,time points also include the middle of the maintenance course and 3 months after the end of maintenance.

An additional blood examination will be used to examine NETs formation against tumor cell lines and their ability to kill tumor cells.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Israel
  • Tel-Aviv, Israel, 64239
    • Recruiting
    • Department of pediatric hemato-oncology, Tel-Aviv Sourasky Medical Center
    • Contact: Sivan Achituv, MD; Phone Number: 972-527360718; Email: sivanbrg@netvision.net.il
    • Contact: Ronit Elhasid, MD; Phone Number: 972-3-6974252; Email: ronite@tasmc.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All pediatric patients from birth to 21 years, male and female, undergoing chemotherapy treatment for solid and hematological malignancies.

Description

Inclusion Criteria:

Included in the study were patients with:

• Acute lymphoblastic leukemia or acute myelogenous leukemia.
• Hodgkin's lymphoma or non-Hodgkin's lymphoma.
• Primary bone sarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma, neuroblastoma, Wilms' tumor, hepatoblastoma or hepatocellular carcinoma, hystiocytosis, and germ cell tumors.
• Medulloblastoma, low grade glioma, high grade glioma, ependymoma, and embryonal and pineal region tumors.

Exclusion Criteria:

• A severe background disease that may affect Neutrophil function (e.g., diabetes, lupus).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Meir Medical Center; Max Planck Institute for Infection Biology
• Investigators: Principal Investigator: Sivan Achituv, MD, The department of pediatric hemato-oncology, Dana Childrens' Hospital, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Anticipated): February 1, 2015
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: February 12, 2012
• First Submitted That Met QC Criteria: February 14, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Estimate): February 15, 2012
• Last Update Submitted That Met QC Criteria: February 14, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: children; malignancy; neutrophil; neutrophil extracellular traps; superoxide production; hydrogen peroxide production; chemotaxis; myeloperoxidase; immunosurveillance; cancer cell lines
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: 0592-11-TLV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No