Ignite Creation Date:
2024-05-05 @ 7:29 PM
Last Modification Date:
2024-10-26 @ 9:49 AM
Study NCT ID:
NCT00682799
Status:
COMPLETED
Last Update Posted:
2015-01-15
First Post:
2008-05-16
Brief Title:
Serial Analysis of Chimerism in Patients With Refractory Cytopenia RC Transplanted With Reduced Intensity Conditioning RIC
Sponsor:
Charlotte Niemeyer MD
Organization:
University Hospital Freiburg
Study Overview
Official Title:
Serial Analysis of Chimerism in Patients With Refractory Cytopenia RC Transplanted With Reduced Intensity Conditioning RIC EWOG MDS SCT RC RIC-06
Status:
COMPLETED
Status Verified Date:
2015-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a prospective non-randomized multi-center multi-national study to evaluate the chimerism measured by STR and SNP in patients with hypoplastic RC and normal karyotype transplanted with a preparative regimen of reduced intensity
Primary objectives
To study hematopoietic chimerism in whole blood and different cell population CD14 CD15 CD 56 CD3 CD19 as well as in dendritic cells and regulatory T-cells after SCT with RIC in patients with RC
To compare the results of chimerism obtained with standard STR PCR sensitivity 1 with those obtained with SNP PCR sensitivity 01- 001
Secondary objectives
To evaluate the relationship between mixed chimerism and hematological engraftment OS and EFS
To study the impact of mixed chimerism in plasmacytoid dendritic and regulatory T-cells on the incidence of acute and chronic GVHD
Primary objectives
To study hematopoietic chimerism in whole blood and different cell population CD14 CD15 CD 56 CD3 CD19 as well as in dendritic cells and regulatory T-cells after SCT with RIC in patients with RC
To compare the results of chimerism obtained with standard STR PCR sensitivity 1 with those obtained with SNP PCR sensitivity 01- 001
Secondary objectives
To evaluate the relationship between mixed chimerism and hematological engraftment OS and EFS
To study the impact of mixed chimerism in plasmacytoid dendritic and regulatory T-cells on the incidence of acute and chronic GVHD
Detailed Description:
Research Question 311 Chimerism and post transplant outcome During the past 3 decades SCT has become a well established treatment procedure for many malignant and hematopoietic disorders in children and adults1-8 After transplantation it has been of central interest whether the newly developed hematopoietic system is of recipient or donor origin The investigations of the genotypic origin of post transplant hematopoiesis are called chimerism analysis Originally it was believed that complete donor hematopoiesis is essential to maintain engraftment after allogeneic SCT in humans9 In the last decades however it became evident that donor and recipient hematopoiesis could coexist after allo-SCT in the recipient This state of coexistence of hematopoietic cells is called mixed chimerism which might end in an autologous recovery In patients with refractory cytopenia SCT after myeloablative conditioning regimen allowed prompt and sustained engraftment in virtually all patients In this disease relapse has become a very rare event Consequently transplant related mortality and long term squeals have become major obstacles yet to be overcome to improve the childrens well being and the prognosis of the disease In SCT with RIC the reduction of early and late toxicity may be counterbalanced by delayed engraftment graft rejection mixed chimerism and GVHD
Graft rejection It is well known that less myeloablative conditioning regimens predispose for a higher rate of mixed chimerism Consequently graft rejection or non engraftment is a major cause of treatment failure
Sensitization to minor histocompatibility antigens by prior transfusions of blood products can increase this risk The rapid development of complete chimerism in NK-cells and T-cells seems to play an important role to achieve sustained engraftment specifically in patients transplanted with a dose reduced preparative regimen Therefore it is important to elucidate the development of post transplant chimerism in different cell subpopulations This will allow following and documenting proper engraftment and will detect early hints of ongoing graft rejection
Graft versus host disease The occurrence of GVHD is influenced by many well known factors Although the use of nonmyeloablative SCT can reduce the severity of GVHD GVHD remains a major complication In our pilot study using the reduced intensity preparative regimen in RC the probability for developing GVHD grade IIIV was 048 It is accepted that in comparison to myeloablative SCT in reduced intensity preparative regimens higher proportions of host immune hematopoietic cells may persist While donor-derived alloreactive lymphocytes are being infused these autologous cells might possibly serve as host antigen presentation for continuous stimulation of donor T-cells Consequently it was speculated by the group Shapira and Slavin10 that GVHD may be similarly amplified by reduced conditioning followed by intentional administration of host cells This hypothesis was tested in a preclinical animal model Increased incidence of GVHD higher mortality and increased levels of chimerism were observed in recipients reconstituted with additional host cells particularly with non-irradiated spleen cells Graft-versus-Leukaemia GVL effect was not impaired by post transplant cell administration These results suggested that GVHD may be amplified by recipient cell infusion using either irradiated or viable stimulatory host cells This could possibly explain the higher than anticipated incidence of GVHD and consequently the rapid displacement of host cells with conversion to 100 donor type cells in reduced intensity SCT The present study will therefore investigate whether autologous antigen presenting cells Auto-APC do survive the conditioning regimen and favour to occurrence of GVHD
Graft rejection It is well known that less myeloablative conditioning regimens predispose for a higher rate of mixed chimerism Consequently graft rejection or non engraftment is a major cause of treatment failure
Sensitization to minor histocompatibility antigens by prior transfusions of blood products can increase this risk The rapid development of complete chimerism in NK-cells and T-cells seems to play an important role to achieve sustained engraftment specifically in patients transplanted with a dose reduced preparative regimen Therefore it is important to elucidate the development of post transplant chimerism in different cell subpopulations This will allow following and documenting proper engraftment and will detect early hints of ongoing graft rejection
Graft versus host disease The occurrence of GVHD is influenced by many well known factors Although the use of nonmyeloablative SCT can reduce the severity of GVHD GVHD remains a major complication In our pilot study using the reduced intensity preparative regimen in RC the probability for developing GVHD grade IIIV was 048 It is accepted that in comparison to myeloablative SCT in reduced intensity preparative regimens higher proportions of host immune hematopoietic cells may persist While donor-derived alloreactive lymphocytes are being infused these autologous cells might possibly serve as host antigen presentation for continuous stimulation of donor T-cells Consequently it was speculated by the group Shapira and Slavin10 that GVHD may be similarly amplified by reduced conditioning followed by intentional administration of host cells This hypothesis was tested in a preclinical animal model Increased incidence of GVHD higher mortality and increased levels of chimerism were observed in recipients reconstituted with additional host cells particularly with non-irradiated spleen cells Graft-versus-Leukaemia GVL effect was not impaired by post transplant cell administration These results suggested that GVHD may be amplified by recipient cell infusion using either irradiated or viable stimulatory host cells This could possibly explain the higher than anticipated incidence of GVHD and consequently the rapid displacement of host cells with conversion to 100 donor type cells in reduced intensity SCT The present study will therefore investigate whether autologous antigen presenting cells Auto-APC do survive the conditioning regimen and favour to occurrence of GVHD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None