The Role of NK Cells to Detect Blood Infection in ALL.

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

The Role of Natural Killer Cell Profiling in Predictions of Blood Stream Infection and Antibiotic Resistance in Acute Lymphoblastic Leukemia Patients Post Chemotherapy.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06160115
• Other study ID #: NK cells for infection in ALL
• Status: Not yet recruiting
• Start date: February 1, 2024
• Est. completion date: April 1, 2025

Study information

• Verified date: November 2023
• Source: Assiut University
• Contact: Mostafa S Mohamed Ahmed, Resident
• Phone: 1015277059
• Email: nastrid50[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

1. Assess possibility of prediction of blood stream infections in ALL patients by profiling of NK cells using flow cytometry.

2. Assess the role of NK cells in development of drug resistance post chemotherapy.

Description:

Acute lymphoblastic leukemia (ALL) is the most common malignancy affecting children accounting for approximately 30% of childhood cancers (Zeng XL et al, 2023 ALL is characterized by chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells (Fujita, Sousa-Pereira et al. 2021).

ALL is categorized in B-Lymphoblastic Leukemia (B-ALL) And T-Lymphoblastic Leukemia (T-ALL), originated from B- and T-Lineage lymphoid precursor cells, respectively (Chiaretti S et al, 2014).

Recent progress in treatment of ALL has increased the survival rate significantly. The 5-year survival rate in children with ALL is approximately 90% (Paul 2016).

Bloodstream infection is a major cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (Wolf, Tang et al. 2017).

This is caused by severe and prolonged immunosuppression due to neutropenia, and other chemotherapy-induced alterations of host defense mechanisms The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics One of the crucial first line of defense against bloodstream infections in the immune system are Natural Killer cells Natural killer (NK) cells are lymphocytes of the innate immune system that are critical in host defense and immune regulation They can mediate spontaneous cytotoxicity towards malignant cells and microbes, and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses

NK cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 56
• Est. completion date: April 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Years to 17 Years

Eligibility

Inclusion Criteria:

• Patients aged less than 17 years diagnosed as Acute Lymphoblastic Leukemia and on chemotherapy, who are positive for blood stream infection.

Exclusion Criteria:

1. Patients over 17 years of age.

2. Presence of other hematological malignancies or history of other malignancies.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Bloodstream Infection
• Communicable Diseases
• Infections
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Sepsis

Intervention

Device:
• Flow cytometry
Profiling of NK cells using flow cytometry on peripheral blood and bone marrow aspirate samples. Isolation and identification of pathogens causing BSI and bacterial drug susceptibility testing using VITEK compact fully automatic microbial identification instrument.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (10)

Ammann RA, Laws HJ, Schrey D, Ehlert K, Moser O, Dilloo D, Bode U, Wawer A, Schrauder A, Cario G, Laengler A, Graf N, Furtwangler R, Simon A. Bloodstream infection in paediatric cancer centres--leukaemia and relapsed malignancies are independent risk fact — View Citation

Bayatipoor H, Mehdizadeh S, Jafarpour R, Shojaei Z, Pashangzadeh S, Motallebnezhad M. Role of NKT cells in cancer immunotherapy-from bench to bed. Med Oncol. 2022 Dec 2;40(1):29. doi: 10.1007/s12032-022-01888-5. — View Citation

Bi J, Tian Z. NK Cell Exhaustion. Front Immunol. 2017 Jun 28;8:760. doi: 10.3389/fimmu.2017.00760. eCollection 2017. — View Citation

Campbell KS, Hasegawa J. Natural killer cell biology: an update and future directions. J Allergy Clin Immunol. 2013 Sep;132(3):536-544. doi: 10.1016/j.jaci.2013.07.006. Epub 2013 Jul 30. — View Citation

Fujita TC, Sousa-Pereira N, Amarante MK, Watanabe MAE. Acute lymphoid leukemia etiopathogenesis. Mol Biol Rep. 2021 Jan;48(1):817-822. doi: 10.1007/s11033-020-06073-3. Epub 2021 Jan 13. — View Citation

Gupta DG, Varma N, Naseem S, Sachdeva MUS, Bose P, Binota J, Kumar A, Gupta M, Rana P, Sonam P, Malhotra P, Trehan A, Khadwal A, Varma S. Characterization of Immunophenotypic Aberrancies with Respect to Common Fusion Transcripts in B-Cell Precursor Acute — View Citation

Karaman R, Jubeh B, Breijyeh Z. Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches. Molecules. 2020 Jun 23;25(12):2888. doi: 10.3390/molecules25122888. — View Citation

Littera R, Chessa L, Deidda S, Angioni G, Campagna M, Lai S, Melis M, Cipri S, Firinu D, Santus S, Lai A, Porcella R, Rassu S, Meloni F, Schirru D, Cordeddu W, Kowalik MA, Ragatzu P, Vacca M, Cannas F, Alba F, Carta MG, Del Giacco S, Restivo A, Deidda S, — View Citation

Lodoen MB, Lanier LL. Natural killer cells as an initial defense against pathogens. Curr Opin Immunol. 2006 Aug;18(4):391-8. doi: 10.1016/j.coi.2006.05.002. Epub 2006 Jun 12. — View Citation

Matthiesen S, Zaeck L, Franzke K, Jahnke R, Fricke C, Mauermeir M, Finke S, Luhrmann A, Knittler MR. Coxiella burnetii-Infected NK Cells Release Infectious Bacteria by Degranulation. Infect Immun. 2020 Oct 19;88(11):e00172-20. doi: 10.1128/IAI.00172-20. P — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who test positive for bloodstream infection and NK cells profile	Assess the number of participants who are positive for bloodstream infection in microbial identification instrument, then comparison of Flow cytometry results for CD16 and CD56 to identify role of NK cells.	Baseline