Pre-engraftment Cytomegalovirus DNAemia

CMV DNAemia Pre-engraftment Clinical Trial

Official title:

Pre-engraftment Cytomegalovirus DNAemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Incidence, Risk Factors and Clinical Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03889028
• Other study ID #: NAV-CMV-2019
• Status: Completed
• Start date: September 2, 2019
• Est. completion date: September 1, 2020

Study information

• Verified date: November 2020
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.Both high-level and persistent virus DNAemia are known risk factors for CMV end-organ disease and perhaps non-relapse mortality. CMV DNAemia is usually documented after engraftment, but it may occur before. The virological features and clinical consequences of these latter early-onset episodes remain largely unexplored. The U.S. Food and Drug Administration (FDA) has recently approved letermovir for prophylaxis of CMV infection and disease in adult CMV-seropositive allo-HSCT recipients (PREVYMIS™, Merck & Co., New Jersey, USA). In accordance with the design of the phase III, double-blind trial the drug may be administered as early as the day of transplant and no later than 28 days post-transplant. Nevertheless, the timing of drug inception should be contingent on the clinical impact of very early episodes of CMV DNAemia. In a recent work from our group (single-center study) we found that a total 38 out of the 197 patients in our series developed CMV DNAemia before engraftment (cumulative incidence (CI), 19%; 95% CI, 10-30.3%). Nine episodes of CMV DNAemia were detected prior to the time of donor progenitor cell infusion. A greater number of post-engraftment episodes required preemptive antiviral therapy compared with pre-engraftment episodes (62.5% vs 44.7%; P=0.05). The cellular content of the donor progenitor cell infusion and transplant characteristics of patients did not differ between patients with pre- or post-engraftment CMV DNAemia. The cumulative incidence of overall mortality by days 100 and 365, aGvHD by day 100 and relapse by day 365 were not significantly different between patients with pre-engraftment or post-engraftment CMV DNAemia. Our study was limited by the retrospective and single-center design and the scarce number of pre-engraftment CMV DNAemia episodes included; therefore, the results may not be extrapolated to other transplantation centers or patient cohorts. Further retrospective and prospective studies are thus required to validate the data presented herein.

Description:

Episodes of CMV DNAemia developing prior to engraftment (pre-CMV DNAemia), which usually occur between the third and fourth week after allo-HSCT, may conceivably have a different course from episodes emerging after engraftment once patients have begun to expand donor-derived T cells (post-CMV DNAemia). Thus, whether the precise timing of Letermovir treatment initiation should matter will ultimately depend on the impact of CMV DNAemia episodes developing prior to engraftment on clinical outcomes. There is limited information available on this topic. Here, we conducted a retrospective multicenter, non-interventional study to further address this issue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 878
• Est. completion date: September 1, 2020
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Recipients >18 years old

• CMV seropositive recipients and/or donors

• First allo-HSCT (T cell replete)

• CMV DNA load monitoring by real-time PCR

Exclusion Criteria:

• Recipients < 18 years

• CMV seronegative donors and recipients.

• No CMV DNA load monitoring

Related Conditions & MeSH terms

• CMV DNAemia Pre-engraftment

Locations

Country	Name	City	State
Spain	Clinical University Hospital of Valencia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para la Investigación del Hospital Clínico de Valencia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Engraftment (Days) Stratified by CMV DNaemia Occurring Before or After Neutrophil's Engraftment	absolute neutrophil count =500/mm3 on 3 consecutive days,, the first of which being time of engraftment.	30 days
Secondary	Overall Mortality	total number of deaths from any cause	1 year
Secondary	Non-relapse Mortality	total number of deaths without relapse or underlying disease progression	1 year