Clinical trial NCT03294824: Non Randomized Comparative Study With Control
Official title: Study of Natural Killer Immunity During Infections With CMV or AdV After Allogeneic Hematopoietic Stem Cells
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Keywords: NK cells
Cytomegalovirus
adenovirus
Allogeneic transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-09-27
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Allogeneic HSCT for malignant or non malignant hematological disease in adult patients

Brief summary: NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal tolerance. They belong to innate immune cells but they have a link with adaptative immunity. Indeed, after some viral infections such as CMV, Chikungunya, B hepatitis etc, a subset of NKG2C+ NK cells expands and can transfer, in murine models, a " memory " that can better control CMV infections. CMV reactivation is a major cause of morbidity and mortality after allogeneic hematopoietic ste cell transplantation in humans. The aim of this prospective study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of CMV but also Adenovirus after allo HSCT. Peripheral NK cells from 30 and 10 patients who reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and functional studies before and after administration of anti viral drugs) and compared with 30 allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors serologically + for CMV.

Detailed description: For both groups: 28ml of peripheral blood samples are collected at different points. Group 1 : before and after anti viral treatment . Control group 2: one point after allo-HSCT; Control group 3: 1 point before transplant. Phenotypical study of NK cells: activating and inhibitory receptors, activation and differentiation's markers. Phenotypical studies of the ligands on infected cells. Genotypic study of KIR receptors (Kirotype); functional studies: polyfunctionality essay (flow cytometry): degranulation CD107a, IFNg, TNFa production).

Eligibility criteria: Inclusion Criteria:

1. patients who reactivate CMV or AdV after allogeneic HSCT ;

   * Age\>18 years; indication for a antiviral treatment:
   * at least 1 PCR CMV\>1000 copies/ml or 1 PCR ADV\>1000 copies/ml or at least 2 ADV PCR positive - sites (stools, throat, urines);
   * signed informed consent;
2. Control group: allogeneic HSC transplanted patients;

   * Age\>18 years; no CMV or AdV reactivation ;
   * signed informed consent;
3. Healthy donors group: HSC donor;

   * Age\>18 years;
   * signed informed consent

Exclusion Criteria:

none

Primary outcomes:
measure: Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry
timeFrame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
measure: NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells
timeFrame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
Secondary outcomes:
measure: Effect of CMV and AdV infection compared with healthy donors
timeFrame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
measure: In vitro Nk cells ligands analyzes on infected cells by CMV
timeFrame: approximately 18 months after Study Completion Date (last participant's last visit)
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Pitié Salpêtriere
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Stephanie Nguyen Quoc, Doctor
role: PRINCIPAL_INVESTIGATOR
References: