Anti-Infective Agents

All Drugs and Chemicals

Hydrogen Peroxide

Sivan Achituv, MD

Ronit Elhasid, MD

Identifying the post-transplantation phase wherein neutrophils recover their ability to release NETs 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. Therefore, we aim to 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 autologous and allogeneic hematopoietic stem cell transplantation (HSCT).

Although neutrophil engraftment takes place 10 to 14 days after autologous HSCT, and 15 to 30 days after allogeneic HSCT, using an ablative conditioning regimen, neutrophil dysfunction may persist for longer periods. Relatively scant data exists on neutrophil function following HSCT. After autologous HSCT, the respiratory burst and phagocytosis may be decreased for up to 3 months. After allogeneic HSCT, respiratory burst and chemotaxis are generally decreased for 4 to 6 months. Factors such as continuation of chemotherapy, immunosuppression, and GVHD contribute to this prolonged dysfunction. No data exist on reconstitution of NETs following HSCT.

Nets production and other neutrophil functions will be examined at several time points: before transplantation, at neutrophil engraftment, 6 weeks, 3 months, 6 months, 9 months, 1 year, 1.5 years, 2 years, and 3 years post-transplant, or until normalization of neutrophil function at 2 consecutive time points. Data gathered on patients will cover:

1. Demographics.
2. Tumor histological type, staging, previous chemotherapy regimen, and initial response to treatment.
3. HSCT procedure - type of conditioning regimen, type of graft (autologous or allogeneic - related donor/unrelated donor/cord blood), use of bone marrow stem cells (SCs) or peripheral mobilized SCs, number of SCs given, post-transplant immunosuppression, post-transplant prophylactic antimicrobial treatment, infections during the study period, and GVHD occurrence and treatment.

Neutrophil examinations will be done in collaboration with the Laboratory for Leukocyte Function of the Department of Pediatrics, Meir Medical Center, Kfar Saba and NETs visualization with the Department of Cellular Microbiology at the Max Planck Institute for Infection Biology, Berlin.

10cc of peripheral venous blood will be collected from each patient at several time points: Before transplant, at neutrophil engraftment, 6 weeks, 3 months, 4 months, 6 months, 9 months, 1 year, 1.5 years, 2 years, and 3 years post-transplant, or until normalization of NETs formation in 2 consecutive examinations.

Neutrophil Extracellular Traps Formation Post-hematopoietic Stem Cell Transplantation

Neutrophil Extracellular Traps (NETs) Formation Post-hematopoietic Stem Cell Transplantation (HSCT) and Its Relation to Chemotaxis and Creation of Reactive Oxygen Species

Max Planck Institute for Infection Biology

Meir Hospital, Kfar Saba, Israel

Tel-Aviv Sourasky Medical Center

Director, Division of Research and Developement

Heart and Blood Diseases

All Conditions

Thromboembolism

Venous Thromboembolism

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

Patients presenting with venous thromboembolism (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or pulmonary embolism) as detected by ultrasonography, phlebography, computer tomography, or angiography

Charlotte Thålin, M.D., Ph.D.

Håkan Wallén, M.D., Prof.

Lena Gabrielsson

Mårten Söderberg, M.D., Ph.D.

Venous thromboembolism is a common and serious complication in cancer, and is associated with a substantially increased morbidity and mortality. Furthermore, VTE may be the earliest sign of cancer. Recent studies, however, fail to show a clinical benefit of extended cancer screening in this patient population. Better risk prediction models are therefore warranted to identify VTE patients who would benefit from a rapid and extensive cancer screening. Inflammation and hypercoagulability are considered hallmarks of cancer, and emerging light is being shed on the potential of various markers of inflammation and coagulation in cancer diagnostics and prognostics. Among the inflammatory and thrombotic processes linked to cancer is the neutrophil release of web-like nuclear chromatin (DNA and histones), referred to as neutrophil extracellular traps (NETs). Driven by the tumor environment, NETs have recently been shown to play a central role in tumor progression, metastasis, and tumor-associated thrombosis.

The investigators hypothesize that an enhanced inflammatory state may be predictive of an underlying cancer in patients presenting with VTE. The present study is an ongoing prospective study with the primary aim to investigate the diagnostic potential of markers of inflammation, including markers of NETs, in detecting occult cancer in patients presenting with VTE. Secondary aims are to include other biomarkers of cancer, and to assess whether any or a combination of these biomarkers may be prognostic of occult cancer, recurrent thrombotic events, mortality, or cancer disease progression in VTE patients with an underlying malignancy.

Identification of Novel Biomarkers to Aid in the Detection of Occult Cancer in Patients With Venous Thromboembolism

Patients diagnosed with VTE will be referred for a limited cancer screening according to current guidelines. Cancer diagnosis - if not present at inclusion - will be obtained during a two-year follow-up from hospital records and/or the Swedish cancer registry

Recurrent thrombotic event (arterial or venous thrombosis) will be obtained during a two-year follow-up from hospital records and/or the Swedish national patient registry

All-cause mortality will be obtained during a two-year follow-up from hospital records and/or the Swedish death registry

Patients with cancer progression will be identified during a two-year follow-up from hospital records and/or the Swedish cancer registry

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neutrophil Extracellular Traps Formation Post-hematopoietic Stem Cell Transplantation	NCT01491230	Childhood Cance...		- 21 Years	Tel-Aviv Sourasky Medical Center
Identification of Novel Biomarkers to Aid in the Detection of Occult Cancer in Patients With Venous Thromboembolism	NCT03781531	Cancer Venous Thromboe...		18 Years -	Danderyd Hospital

Spots Global Cancer Trial Database for neutrophil extracellular traps