Cytomegalovirus Infections
Conditions
Keywords
Ganciclovir-resistant CMV, Cytomegalovirus, Solid Organ Transplant, Ganciclovir, Ganciclovir-refractory CMV, Hematopoietic Stem Cell Transplant
Brief summary
The ReCySOHT study is a multicenter, retrospective, observational case-control study on the risk factors for developing a ganciclovir-resistant/refractory (GCV-RR) cytomegalovirus infection in patients receiving solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). Aims of the study are to investigate the incidence of and risk factors for GCV-RR CMV infection in SOT recipients and HSCT patients in order to design further studies aimed at preventing and improving the patient management of GCV-RR CMV infections.
Detailed description
Cytomegalovirus (CMV) is an important cause of morbidity and mortality in solid organ transplant (SOT) patients and hematopoietic stem cell transplant (HSCT) patients. Ganciclovir (GCV) is the first line therapy for treatment and prevention of CMV infection in SOT and HSCT recipients, with established efficacy and relatively safe profile. Ganciclovir-resistant or refractory (GCV-RR) CMV is an uncommon but frightening clinical problem due to limited, toxic and less effective therapeutic alternative drugs. Indeed, some studies indicate that GCV-RR is associated with significant additional attributable morbidity and mortality in SOT and HSCT recipients compared with ganciclovir susceptible (GCV-S) CMV disease. Few data are available about the incidence of GCV-RR-CMV in SOT and HSCT patients showing a range from 0% to 3% . The serological mismatch group and the type of SOT have been reported as the main factors influencing such range. Indeed, in one of the largest experience now available in SOT, the incidence of GCV-resistant (GCV-RT) CMV infection accounted up to 12% in a cohort of lung transplant recipients. Among HSCT patients, haploidentical, allogeneic unrelated, and cord blood HSCT have been associated with increased risk of GCV-RR CMV infection. Among risk factors for GCV-RR, high-risk D/R subset (R- in SOT and R+ in HSCT), high viral loads, inadequate drug delivery, increased durations of antiviral drug exposure and the use of more potent immunosuppressive regimens have been reported. However, these reports come from small, monocentric experiences with a limited number of cases, providing a fragmentary picture of the overall burden and epidemiological characteristics of GCV-RR in transplant patients. Information of the epidemiological background of GCV-RR after transplantation could be helpful in improving preventive management and reducing the emergence of GCV-RT episodes. Indeed, studies investigating viral genetic alterations showed that mutations conferring ganciclovir resistance are not present at baseline but emerge and become amplified over time, especially in the presence of an incompletely suppressive drug exposure. The GCV-RT is due to mutations in UL97 and UL54 genes. UL97 mutations confer various degrees of phenotypic resistance to ganciclovir. Mutations in UL54 determine higher-level resistance to ganciclovir and usually appear as a second step after mutations in UL97. The investigators carry-out a multicenter retrospective observational study to define incidence of GCV-RR CMV-infection in SOT and HSCT patients and to identify the risk factors for its development in SOT and HSCT recipients. Data from this study could be useful to design further studies aimed at preventing and improving the patient management of GCV-RR CMV infections.
Interventions
None listed
Sponsors
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All adult (≥ 18 years) patients who underwent SOT or HSCT developing CMV-infection treated with GC/VGC * Ability to understand the purpose of the study and provide signed and dated informed consent
Exclusion criteria
* Lack of clinical and/or laboratory data regarding the type of CMV event * Lack of the serological mismatch at transplantation * Lack of the type of SOT or HSCT * Lack of the patient and graft outcome at 30, 60 or 90 days after CMV event diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To define incidence of GCV-RR CMV-infection in SOT and HSCT patients | Through study completion, an average of 1 year | To define incidence of GCV-RR CMV-infection in SOT and HSCT patients |
| To define the risk factors for GCV-RR CMV-infection development in SOT and HSCT patients | Through study completion, an average of 1 year | To define the risk factors for GCV-RR CMV-infection development in SOT and HSCT patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare type of CMV episode between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare type of CMV episode: infection or disease (the last cathegorized as CMV syndrome or Tissue invasion) between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To compare virological cure between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare virological cure at 30, 60 and 90 days after CMV infection diagnosis and relapse of CMV infection between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To compare clinical cure between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare clinical cure at 30, 60 and 90 days after CMV infection diagnosis between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To compare graft outcome between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare graft failure rate and the need of re-transplant between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To compare the need of ICU and hospital stay between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare total length of ICU and hospital stay between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To compare the need of readmission in ICU and/or hospital between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare the need of readmission in ICU and/or hospital between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To compare all-cause mortality between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection | Through study completion, an average of 1 year | To compare all-cause mortality during infection episode and follow-up (30, 60, 90 days after the first CMV infection diagnosis) between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection |
| To describe the therapeutic management of GCV-RR CMV-infection | Through study completion, an average of 1 year | To describe the therapeutic management of GCV-RR CMV-infection including the use of CMV-specific T-cell assay |
Countries
Belgium, Finland, France, Italy, Portugal, Spain, Switzerland, United Kingdom, United States
Contacts
CONTACTRenato Pascale, MD
CONTACTMaddalena Giannella, MD, PhD
PRINCIPAL_INVESTIGATORRenato Pascale, MD
IRCCS AOUBO
Outcome results
None listed