Bone Marrow Failure Syndromes, Graft vs Host Disease, Immune Deficiency Disease, Leukemia, Myeloid, Acute, Opportunistic Infections, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Conditions
Keywords
CD45RA-depletion, TCR-alpha/beta depletion, Hematopoietic Stem Cell Transplantation, immune reconstitution, Graft Enhancement, Immunologic, Immunocompromized Host
Brief summary
The stud will evaluate whether infusions of CD45RA-depleted lymphocytes from the donor early post-transplant is a safe way to improve immunity to common infections in recipients of TCR-alpha/beta depleted hematopoietic stem cell grafts.
Detailed description
Graft-versus-host disease (GVHD) remains the most important direct complication of hematopoietic stem cell transplantation. Methods used to prevent GVHD include diverse pharmacologic interventions and ex vivo methods of T-cell depletion, the latter being the most effective ones. Historically depletion of T-cells from the graft is associated with increased rate of graft failure, relapse of malignant disease and prolonged immune deficiency. Selective depletion of TCR-alpha/beta T-lymphocytes is a new method of hematopoietic stem cell graft manipulation which is thought to conserve important cell populations, e.g. NK cells and gamma/delta T cells within the graft. Preliminary results suggest that TCR alpha/beta depletion ensures high engraftment rate, low early mortality and good control of GVHD. The problem of delayed immune reconstitution and life-threatening viral infections remains incompletely resolved. Depletion of naive (CD45RA-positive) T-cells was developed as a new method of graft manipulation to prevent GVHD. Research data indicate that alloreactivity is associated mainly with naive T-cell fraction. In vitro depletion of CD45RA lowers significantly the alloreactive response while retaining reactivity to pathogens. In the current protocol we plan to test whether relatively low doses of CD45RA-depleted mononuclear cells can be safely infused after TCR-alpha/beta depleted transplantation. The biologic readout for the protocol will be quantitative assessment of T-cell reactivity to common pathogens after infusion.
Interventions
Infusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells
Sponsors
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
* recipient of allogeneic hematopoietic stem cell graft from haploidentical or matched unrelated donor * TCR alpha/beta depletion of the hematopoietic stem cell graft * CMV-seropositive donor * stable hematopoietic engraftment
Exclusion criteria
* active graft-versus-host disease grade 2-4 * any systemic immune suppressive therapy except calcineurin inhibitor monotherapy * uncontrolled sepsis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of grade 2-4 acute graft-versus-host disease | 100 days | Cumulative incidence (competing risk model) of acute graft-versus-host disease |
| Immune reconstitution (Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay) | 120 days | Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-year survival | 1 year | Kaplan-Meyer estimate of overall survival |
| Transplant-related mortality | 1-year | Cumulative incidence (competing risk model) of transplant-related mortality |
| Incidence of chronic graft-versus-host disease | 1 year | Cumulative incidence (competing risk model) of chronic graft-versus-host disease |
Countries
Russia
Outcome results
None listed