Pre-engraftment Cytomegalovirus DNAemia

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

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.

Study Overview

• Status: Completed
• Conditions: CMV DNAemia Pre-engraftment

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 878

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46010
    • Clinical University Hospital of Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All consecutive allo-HSCT recipients at risk of CMV infection allografted from 1st January 2010 until 31th December 2017 in Spanish transplant centers

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Mortality	total number of deaths from any cause	1 year
Non-relapse Mortality	total number of deaths without relapse or underlying disease progression	1 year

Collaborators and Investigators

• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 2, 2019
• Primary Completion (ACTUAL): September 1, 2020
• Study Completion (ACTUAL): September 1, 2020

Study Registration Dates

• First Submitted: March 22, 2019
• First Submitted That Met QC Criteria: March 22, 2019
• First Posted (ACTUAL): March 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2020
• Last Update Submitted That Met QC Criteria: November 18, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: NAV-CMV-2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No