Immune Reconstitution to CMV After HSCT: Impact of Clinical Factors and Therapy Strategies

Immune Reconstitution to Cytomegalovirus After Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Clinical Factors and Therapy Strategies

Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The course and outcome of CMV infection are different clinically, and the mechanism of CMV infection after transplantation has not been clarified. Reconstitution of cellular immunity after HSCT is a critical determinant of the control of CMV infection.

Investigators will dynamically monitor the CMV-specific cellular immune reconstitution after HSCT，and analyze the clinical factors and therapy strategies affecting recovery of CMV-specific immunity during 1 year after HSCT.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hematopoietic Stem Cell Transplantation; CMV Infection
• Intervention / Treatment: Drug: Letermovir

Detailed Description

Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The course and outcome of CMV infection are different clinically, and the mechanism of CMV infection after transplantation has not been clarified. Reconstitution of cellular immunity after HSCT is a critical determinant of the control of CMV infection.

Investigators will collect peripheral blood at 1 month, 2 month, 3 month, and 6 month after HSCT from the participated patients, and dynamically monitor the CMV-specific T and NK cellular immune reconstitution.

Investigators will also analyze the clinical factors and therapy strategies affecting recovery of CMV-specific immunity during 1 year after HSCT.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • People's Hospital of Peking University
  • Beijing
    • Beijing, Beijing, China, 100044
      • Department of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Adult patients who received allogeneic HSCT.

Description

Inclusion Criteria:

• Be receiving a first allogeneic HSCT.
• Is male or female, from 14 years to any years of age inclusive.
• The participant (or legally acceptable representative) agree for cellular immune investigation and has provided documented informed consent/assent for the study.

Exclusion Criteria:

• Received a previous allogeneic HSCT (Note: Receipt of a previous autologous HSCT is acceptable).
• Has a history of CMV end-organ disease within 6 months prior to allocation.
• Has severe organ (hepatic , renal, cardical) insufficiency within 5 days prior to allocation.
• Any rapidly-progressing disease or immediately life-threatening illness.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Letermovir Group; HSCT recipients who received letermovir prophylaxis	Drug: Letermovir; Patients received letermovir as prophylaxis or received preemptive therapy for CMV depends on clinical needs and patients' wishes
Preemptive therapy Group; HSCT recipients who received PCR-guided preemptive therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of clinically significant CMV infection (CSI)	Clinically significant CMV infection (CSI) is defined as the administration of antiviral therapy as preemptive therapy for CMV DNAemia or treatment for CMV disease.	6 months after HSCT
Incidence of refractory CMV infection and CMV disease	Refractory CMV infection is defined as a persistent viral load (CMV viral load at the same level or higher than the peak viral load within 1 week but <1 log10 increase in CMV DNA titers done in the same laboratory and with the same assay) after at least 2 weeks of appropriately dosed antiviral therapy.	6 months after HSCT
Numbers of immune cells in peripheral blood	PBMCs from HSCT recipients were collected at 1 month, 2 month, 3 month, and 6 month after HSCT, and tested for NK cells, T cells, CMV-specific T cells and their subsets.	6 months after HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-ralated mortality	Treatment-ralated mortality	Through study completion, an average of 1 year
Overall survival	Overall survival	Through study completion, an average of 1 year
Incidence of other viral infection and viral-associated disease	Other viral infection and viral-associated diseases including EBV, ADV, HHV-6, BKV and HSV	6 months after HSCT

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 25, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 19, 2022

Study Record Updates

• Last Update Posted (Actual): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 30, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Letermovir
• Other Study ID Numbers: 2021PHB423-001

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