CMV
Conditions
Keywords
Citomegalovirus, Haploidentical, Hematopoietic Stem Cell Transplantation
Brief summary
Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplantation(HSCT). Recently, strategies based on immunotherapy adoptive cells (IAC) with anti-CMV Cytolitic T Lymphocytes (CMV-CTLs) has been incorporated to prevent or treat CMV after HSCT. The aim to study donor derived CMV-CTLs after haploidentical HSCT (HAPLO) as prophylaxis for CMV infection in transplant patients. CMV-CTLs will be administer at day 21 (+-7 days) post-HAPLO. CMV DNA levels with quantitative PCR will be weekly monitored.
Detailed description
In HAPLO, CMV infection and disease are more frequent than in other type of HSCT, this is related to delayed immune reconstitution after transplant increasing post-transplant infectious complications. Approximately 60% of patients reactivated CMV infection after HAPLO and 15%, developed CMV disease afecting organs and causing the death of the patient in 8% of CMV disease cases. If patient and donor are eligible, it will take 1x10\^9 cells from donor leukapheresis. Donor cells will be selected and procesed by CliniMACs PRODIGY and after 12h it will obtain 7mL of CMV-CTLs. It will use 6mL of CMV-CTLs to infused a dose of 1x10\^5 cells/kg in our patient. The donor derived CMV-CTL cells will be transfused into the patients' intravenous line. The patients will receive the dose of CMV-CTL cells when they are sero-positive for CMV-DNA 21 (+- 7 days) days after transplant. The CMV-DNA levels will be monitored weekly for at least 100 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then the patient will receive treatment with anti-CMV comercial drugs.
Interventions
BIOLOGICALCMV CTLs
The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when their donors are sero-positive for CMV-DNA 21 days after transplant. The CMV-DNA levels will be monitored weekly for at least 100 days after the HAPLO. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive a CMV specific antiviral drug.
Sponsors
Instituto de Investigación Marqués de Valdecilla
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients who received an alogeneic stem cell transplantation from haploidentical donors (HAPLO). * Any source of stem cells (peripheral blood or bone marrow). * CMV-seropositive donors. * Negative pregnancy test in women. * Signed writen informed consent. * DONORS: 1. HLA haploidentical and CMV-seropositve donors. 2. Donor must be checked and suitable. 3. Signed writen informed consent. 4. Donor without active infection evidence at leukapheresis.
Exclusion criteria
* Patients without haploidentical CMV-seropositive donors. * Patients who are not suitable for follow up visits. CMV-CTLs Infusion Criteria: * Hematopoiesis recovery at least partial (neutrophil counts \>0.5x10\^9/L in at least 3 consecutive samples post-transplant). CMV-CTLs NON-Infusion Criteria: * Patients receiving corticosteroid (dose of 0.5mg/kg/day of prednisone or equivalent) at infusion. * ECOG \> or = 3. * Organic toxicities grade \> or = 3. * Patients who received ATG, donor lymphocytes or alemtuzuamb, 28 days pre-infusion. * Patients with uncontroled infection defined by fevers and/or inestability and/or infection not resolved. * Persistent fevers 3 days before infusion. * Acute Graft Versus Host Disease (GVHD) grade II-IV. * Relapse or progression after transplant and before infusion day. * CMV reactivation/infection after transplant and before infusion day. Patients who don´t fill infusion criteria, after day 28 post-HAPLO, will be considered screening failures and will be out of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 100-days incidence of CMV infection | From date of CMV-CTLs infusion to 100 days after transplant | Viral load \>200 copies in 1 sample |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-year incidence of CMV specific antiviral drug use | From date of CMV-CTLs infusion to 1 year after transplant | If viral load \>200 copies in 2 samples or \>1000 in 1 sample, treatment with valganciclovir will be started. Time from CMV-CTLs infusion until valganciclovir start and days of valganciclovir. |
| 1-year incidence of CMV disease | From date of CMV-CTLs infusion to 1 year after transplant | CMV disease P.Lungman criteria. CMV as primary cause of death. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 1-year incidence of CMV-CTLs adverse events | From date of CMV-CTLs infusion to 1 year after transplant | Infusion reactions, causes of death, secondary graft failures and graft versus host disease (GVHD). |
| CMV-CTLs persistence | From date of CMV-CTLs infusion to 2 months after infusion | Expansion of CMV-CTLs detected by flow cytometry. |
| Immune reconstitution post-HAPLO | From date of transplant to day 180 post-transplant | CD3, CD4, CD8, B and NK lymphocyte counts in patient peripheral blood post-transplant (day 30, 60, 90 and 180) detected by flow cytometry. |
Countries
Spain
Contacts
Primary ContactMiriam Sanchez-Escamilla, MD
Backup ContactLucía Lavín Alconero, Phd
Outcome results
None listed