Contributions
Abstract: PB2451
Type: Publication Only
Background
It is known that T-regulatory cells (Treg) play an important role in maintaining tolerance after allo-HSCT. Tregs prevent the development of acute graft-versus-host disease (aGVHD) (Beres & Drobyski, 2013). At the same time these T-cell populations can limit the antitumor response (graft-versus-leukemia, GVL) and that limitation may cause relapses. Here we report the analysis of mixed chimerism in T-reg population and the frequency of relapse in patients with acute leukemia (ALL and AML) after allo-HSCT with comparable levels of donor chimerism.
Aims
To evaluate a possible relationship between the mixed chimerism in Treg cells and the rate of relapses in acute leukemia patients after allo-HSCT.
Methods
The study included 31 patients after allo-HSCT (ALL n = 6, AML n = 25). The median age was 38 years (19-66). Peripheral blood samples for analysis were taken on day 30 after transplantation. Immunomagnetic separation (Miltenyi Biotec, Germany) was used to isolate population with CD4+CD25+ phenotype which is predominantly associated with Treg cells. Extraction of DNA was performed from the obtained cells. Chimerism in DNA samples was determined using the STR-PCR method. The percentage of donor chimerism was calculated using standard procedures (Nollet et al., 2001) Statistical analysis of the data was carried out using SPSS ver 23. (IBM, Chicago, Ill., USA). Еxact Fisher’s test was used to analyze the 2 × 2 contingency tables.
Results
In the patients group with less than 11% of cells with host genotype (more than 89% of cells of donor origin) the relapse rate was significantly higher - 52.6% (10 of 19) than in the other group of patients with 11% and more cells with host genotype - 8.3% (1 of 12), (p = 0.02). At the same time donor chimerism in the unselected bone marrow did not significantly differ between the groups (p = 0.36) and amounted to 100% (75-100%) and 97.5% (90-100%). The study groups were balanced for all other factors that could affect the relapse rate: disease status, graft source, GVHD.
Conclusion
According to our data we proposed that host’s Treg cells are not capable of suppressing GVL that explains significant differences in the frequency of relapses in patients with acute leukemia after allo-HSCT. Predominance of host’s Treg cells may serve as a favorable prognostic sign but this hypothesis needs to be confirmed in the largest cohort of patients.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Allogeneic hematopoietic stem cell transplant, Chimerism, Regulatory T cell
Abstract: PB2451
Type: Publication Only
Background
It is known that T-regulatory cells (Treg) play an important role in maintaining tolerance after allo-HSCT. Tregs prevent the development of acute graft-versus-host disease (aGVHD) (Beres & Drobyski, 2013). At the same time these T-cell populations can limit the antitumor response (graft-versus-leukemia, GVL) and that limitation may cause relapses. Here we report the analysis of mixed chimerism in T-reg population and the frequency of relapse in patients with acute leukemia (ALL and AML) after allo-HSCT with comparable levels of donor chimerism.
Aims
To evaluate a possible relationship between the mixed chimerism in Treg cells and the rate of relapses in acute leukemia patients after allo-HSCT.
Methods
The study included 31 patients after allo-HSCT (ALL n = 6, AML n = 25). The median age was 38 years (19-66). Peripheral blood samples for analysis were taken on day 30 after transplantation. Immunomagnetic separation (Miltenyi Biotec, Germany) was used to isolate population with CD4+CD25+ phenotype which is predominantly associated with Treg cells. Extraction of DNA was performed from the obtained cells. Chimerism in DNA samples was determined using the STR-PCR method. The percentage of donor chimerism was calculated using standard procedures (Nollet et al., 2001) Statistical analysis of the data was carried out using SPSS ver 23. (IBM, Chicago, Ill., USA). Еxact Fisher’s test was used to analyze the 2 × 2 contingency tables.
Results
In the patients group with less than 11% of cells with host genotype (more than 89% of cells of donor origin) the relapse rate was significantly higher - 52.6% (10 of 19) than in the other group of patients with 11% and more cells with host genotype - 8.3% (1 of 12), (p = 0.02). At the same time donor chimerism in the unselected bone marrow did not significantly differ between the groups (p = 0.36) and amounted to 100% (75-100%) and 97.5% (90-100%). The study groups were balanced for all other factors that could affect the relapse rate: disease status, graft source, GVHD.
Conclusion
According to our data we proposed that host’s Treg cells are not capable of suppressing GVL that explains significant differences in the frequency of relapses in patients with acute leukemia after allo-HSCT. Predominance of host’s Treg cells may serve as a favorable prognostic sign but this hypothesis needs to be confirmed in the largest cohort of patients.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Allogeneic hematopoietic stem cell transplant, Chimerism, Regulatory T cell