Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine Models : Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine Models

Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (<300/3microL) without evidence of HIV infection or other known immunodeficiency. Patients with ICL are at risk for opportunistic infections typically associated with HIV/AIDS such as disseminated cryptococcal infection and severe human papillomavirus-related dysplasia. More than 20 years since the description of ICL, its etiology, pathogenesis, and management remain unclear. In this study we propose to administer the combination of granulocyte colony stimulating factor (G-CSF) and plerixafor to ICL patients and healthy volunteers with the objective of harvesting mobilized CD34+ hematopoietic progenitor cells (HPCs) by apheresis for transfer into immunocompromised mice and for study with in vitro assays. The mice studies would serve to investigate thymic development, survival, and trafficking of the mobilized human cells within murine lymphoid and non-lymphoid organs.HPCs are used for various therapies and there is an increasing use of agents that stimulate the bone marrow to produce progenitor cells and move them into the bloodstream where they may be harvested by apheresis. Not all patients respond to GCSF with vigorous HPC mobilization. The binding of chemokine receptor CXCR4 to stromal cell derived factor (SDF-1 or CXCL12) is an important interaction between a hematopoietic progenitor cell and its marrow environment. Plerixafor is a CXCR4 inhibitor which blocks binding to SDF-1 , resulting in the release of HPCs (CD34+) into peripheral circulation. In pharmacodynamic studies of plerixafor in conjunction with G-CSF compared to G-CSF and placebo, a two-fold increase in CD34+ cell count was observed.Due to the important role CXCR4 plays in immune cell trafficking and its potential role in the pathogenesis of ICL, we propose as a secondary objective to assess peripheral CD4 T cell and CD34+ hematopoietic progenitor cell numbers and functions in ICL patients compared to controls following G-CSF and plerixafor administration.Study participants will be screened within 12 weeks prior to the study period. Eligible participants will receive G-CSF for 5 days with hospitalization on Day 4 for plerixafor injection followed by apheresis or large volume blood draw (120 cc) on Day 5. Participants will return for examinations and blood draws on Days 8 and 12..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 17. Apr. Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Lymphopenia Phase: Phase 2 Recruitment Status: Recruiting Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: December 19, 2013, Last downloaded: ClinicalTrials.gov processed this data on April 24, 2024, Last updated: April 24, 2024

Study ID:

NCT02015013 140020 14-I-0020

Veröffentlichungen zur Studie:

Isgro A, Sirianni MC, Gramiccioni C, Mezzaroma I, Fantauzzi A, Aiuti F. Idiopathic CD4+ lymphocytopenia may be due to decreased bone marrow clonogenic capability. Int Arch Allergy Immunol. 2005 Apr;136(4):379-84. doi: 10.1159/000084258. Epub 2005 Mar 2. Fruhwirth M, Clodi K, Heitger A, Neu N. Lymphocyte diversity in a 9-year-old boy with idiopathic CD4+ T cell lymphocytopenia. Int Arch Allergy Immunol. 2001 May;125(1):80-5. doi: 10.1159/000053800. Hubert P, Bergeron F, Ferreira V, Seligmann M, Oksenhendler E, Debre P, Autran B. Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia. Int Immunol. 2000 Apr;12(4):449-57. doi: 10.1093/intimm/12.4.449.

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PPN (Katalog-ID):	CTG001571400