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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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CMV Infection, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Letermovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be receiving a first allogeneic HSCT. Is male or female, from 18 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Letermovir Group<br>HSCT recipients who received letermovir prophylaxis | Drug: Letermovir<br>* Patients received letermovir as prophylaxis or received preemptive therapy for CMV depends on clinical needs and patients' wishes<br>|
| Preemptive therapy Group<br>HSCT recipients who received PCR-guided preemptive therapy | |

What is the study measuring?
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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 | 
| CMV treatment related cost | Medical expenses for direct treatment of CMV infection | Through study completion, an average of 1 year |