Hematopoietic Stem Cell Transplantation
Conditions
Keywords
Graft-Versus-Host-Disease, post-allogeneic transplant, haematopoietic progenitors
Brief summary
The purpose of this study is to determine whether vitamin D is effective in the prevention of graft-versus-host-disease after completion of allogeneic transplant.
Detailed description
The allogeneic transplant of haematopoietic cell is the only treatment option for many malignant blood diseases. Unfortunately, the progression free survival and the quality of life of transplanted patients is limited due to the development of graft-versus-host-disease (GVHD). The development of new prophylaxis strategies of GVHD based in the use of immunomodulator agents (allowing the generation of an immunotolerance state and avoiding the use of immunosuppression) is essential. The GVHD is due to the cytotoxic effect of the donor lymphocytes T against healthy organs and tissues of the receptor. Calcineurin inhibitor combined with methotrexate or antibodies anti-lymphocytes T are used as standard prophylaxis. This type of antibodies has demonstrated efficacy to reduce GVHD, but have not increased survival due to increasing the risk of relapses and serious post-transplant infections. Due to its interactions with VDR (vitamin D receptor) present in immune system cells, vitamin D is able to inhibit the activation of dendritic cells and the proliferation and production of cytokines by lymphocytes T. Based on this effect, the peri- and post- transplant administration of vitamin D might decrease the risk of GVHD in allogeneic transplanted patients, subsequently decreasing the immunosuppressant treatment requirements and improving the prognosis of those patients.
Interventions
DRUG1000IU/day of Vitamine D
Administration of a specified dose of Vitamine D
DRUG5000IU/day of Vitamine D
Administration of a specified dose of Vitamine D
Sponsors
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * The patient should accomplish all the criteria to proceed to an allogeneic transplant * The patient or their legal guardians should signed the informed consent approved by the Ethics Committees of Clinical Trials
Exclusion criteria
* Hypercalcemia ≥ 10.5 mg/dl * Renal insufficiency with creatinine level ≥ 2 x upper limit of normal (1,1 mg/dl) * Participation in others Clinical Trials in which the intervention may affect the result of the study. * Patients receiving GVHD immunoprophylaxis with thymoglobuline or GVHD prophylaxis including in vitro or in vivo lymphocytes T depletion (anti-lymphocyte T globulin, ALG) * Patients receiving a transplant from an haploidentical donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence/severity of Graft-Versus-Host-Disease | Day +150 post-transplant | Number of cases of GVHD/Seriousness graded according to National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dendritic cells | Day +21,+56 and +100 post-transplant | The following markers were used to identify different subpopulations CD16-PB, CD45-V500, HLADR-FITC, BDCA-PE, CD11c-PerCP-Cy5.5, CD86-PE-Cy7, CD123-APC and CD14-APC-H7. Plasmacytoid dendritic cells: HLADR+ CD123++ CD11c- CD16- CD14- BDCA1- CD45+. Monocyte-derived dendritic cells: HLADR+ CD123+d CD11c+ CD16++ CD14-/+d BDCA- CD45+. Myeloid BDCA1 dendritic cells : HLADR+ CD123- CD11c+ CD16- CD14- BDCA+ CD45+ |
| Subpopulations of lymphocytes | Day +21,+56 and +100 post-transplant | To be identified using the combination CD19+CD8-FITC, CD3+CD56-PE, CD4- PerCP-Cy5.5, HLADR-APC T cells: CD3+ (CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD8+, CD3+CD4-CD8+) B cells: CD19+ HLADR+ NK cells: CD3- CD19- CD56+ CD45RA-FITC and CCR7-PE were used to distinguish the repertory of naive/effector/memory of CD4 and CD8 cells. -naive T cells: CD45RA+CCR7+ -effector T cells: CD45RA+CCR7- -central memory T cells: CD45RA-CCR7+ -Peripheral memory T cells: CD45RA-CCR7- |
| Regulatory T cells | Day +21,+56 and +100 post-transplant | after incubation of surface antigens (CD25-FITC, CD127-PE and CD4-PerCP-Cy5.5), cells were washed in PBS and then fixed and permeabilized with FoxP3 Staining Buffer Set (eBiosciences) for FOXP3 staining. phenotype of Treg: CD4+CD25+CD127-/+wFoxP3+ |
| NK markers | Day +21,+56 and +100 post-transplant | using the following combinations: CD94-FITC/CD56-PE/CD3-PerCP-Cy5.5/HLADR-APC CD11a-FITC/CD16-PE/CD3-PerCP-Cy5.5/CD56-APC CD158a-FITC/CD161-PE/CD3-PerCP-Cy5.5/CD56-APC CDNKB1-FITC/NKAT-PE/CD3-PerCP-Cy5.5/CD56-APC We identify NK cells with weak expression of CD56 (CD56 called weak) and those expressing more intensely this marker CD56 bright . In addition the expression of different KIR receptor as CD158a , CD161 , and NKAT2 NKB1 were reported. |
| Serum levels of Th1/Th2 cytokines | Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant | (IL-2, IL-4, IL-6, IL-10, tumor necrosis factor alfa (TNF)-α and interferon gamma (IFN-g)) are determined by flow cytometry using the BD Human Th1/Th2 Cytokine CBA |
| Peak Plasma Concentration (Cmax) of Vitamin D | Day -5 pre-transplant and +1, +7 and +21 post-transplant | Peak Plasma Concentration (Cmax) |
| Area under the plasma concentration of Vitamin D | Day -5 pre-transplant and +1, +7 and +21 post-transplant | Area under the plasma concentration versus time curve (AUC) |
| Bone densitometry changes carried out by protocol in post-transplant period | Day +150 post-transplant | Treatment effect in the subsequent development of osteoporosis |
| Activation of T cells | Day +21,+56 and +100 post-transplant | Activation assays are performed on 500 µl of peripheral blood added in 48-well plates. Peripheral blood is stimulated or not with PMA (20µg/2ml) and ionomycin (0.91 µg/ml). |
Countries
Spain
Outcome results
None listed