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Impact of Pre-Transplant Anti-T Cell Globulin (ATG) on Immune Recovery after Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation.

Servais S, Menten-Dedoyart C, Beguin Y, Seidel L, Gothot A, Daulne C, Willems E, Delens L, Humblet-Baron S, Hannon M, Baron F - PLoS ONE (2015)

Bottom Line: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F).Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells.Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells.

View Article: PubMed Central - PubMed

Affiliation: Hematology Research Unit, GIGA-I3, University of Liège, Liège, Belgium; Bone Marrow Transplantation Unit, Department of Clinical Hematology, CHU of Liège, Liège, Belgium.

ABSTRACT

Background: Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented.

Methods: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F). Detailed phenotypes of circulating T, B, natural killer (NK) and invariant NKT (iNKT) cells were analyzed by multicolor flow cytometry at serial time-points from day 40 to day 365 after transplantation. Thymic function was also assessed by sjTREC quantification. Serious infectious events were collected up to 2 years post-transplantation.

Results: Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells. Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells. Levels of sjTRECs were similar in both cohorts at 1-year after PBSCT, suggesting that ATG-F unlikely impaired thymopoiesis at long-term after PBSCT. Finally, the incidence and rate of serious infections were similar in both groups, while ATG-F patients had a lower incidence of grade II-IV acute graft-versus-host disease.

Conclusions: Pre-transplant ATG-F induces long-lasting modulation of the circulating T-cell pool after myeloablative PBSCT, that may participate in preventing graft-versus-host disease without deeply compromising anti-pathogen defenses.

No MeSH data available.


Related in: MedlinePlus

Lymphoid cell recovery after PBSCT with or without pre-transplant ATG-F.Levels of circulating lymphoid cells in the peripheral blood of ATG-F (blue box) and control (white box) patients are shown. Cell phenotypes were assessed for 27/34, 27/33, 27/31, 26/30, 24/30, 26/29 and 19/25 disease-free survivors in the ATG-F cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively; and for 17/23, 11/19, 10/17, 12/17, 11/17, 8/15 and 5/9 disease-free survivors in the control cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively. Box and whisker plots display the median, 25th and 75thpercentiles of the distribution (box) and whiskers extend to 5th and 95th percentiles. The grey horizontal line and shaded grey area show the median and normal range (from 5th to 95th percentile) in 22 age-matched healthy controls. *p <0.05; ** p<0.01.
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pone.0130026.g001: Lymphoid cell recovery after PBSCT with or without pre-transplant ATG-F.Levels of circulating lymphoid cells in the peripheral blood of ATG-F (blue box) and control (white box) patients are shown. Cell phenotypes were assessed for 27/34, 27/33, 27/31, 26/30, 24/30, 26/29 and 19/25 disease-free survivors in the ATG-F cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively; and for 17/23, 11/19, 10/17, 12/17, 11/17, 8/15 and 5/9 disease-free survivors in the control cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively. Box and whisker plots display the median, 25th and 75thpercentiles of the distribution (box) and whiskers extend to 5th and 95th percentiles. The grey horizontal line and shaded grey area show the median and normal range (from 5th to 95th percentile) in 22 age-matched healthy controls. *p <0.05; ** p<0.01.

Mentions: Recovery of lymphoid cell subsets in the peripheral blood is shown in Fig 1A–1F. ATG-F and control patients had similar levels of circulating lymphoid cells during the first year after PBSCT, except on day 14 when they were lower in ATG-F patients. By assessing lymphoid cell subsets, we did not observe any difference in levels of NK cells (CD3-CD56+) and CD8+T cells (CD3+CD8+) between ATG-F and control patients over the first year after PBSCT, with rapid recovery of these cells in both groups (medians reaching normal values by 40–100 days after PBSCT). To the contrary, CD4+T cells (CD3+CD4+) recovered more slowly in both groups. Further, a more profound CD4+T-cell depletion was observed in ATG-F patients the first 6 months after PBSCT, mostly due to slower recovery of naive (CD3+CD4+CD45RA+) cells. Counts of memory CD4+T cells (CD3+CD4+CD45RO+) were roughly similar in both groups. Regarding B-cell (CD19+) recovery, median B-cell counts reached normal values 1 year after PBSCT in both groups. There was a trend for higher B-cell levels in ATG-F patients, although the difference reached statistical significance only on days 100 and 120 after PBSCT.


Impact of Pre-Transplant Anti-T Cell Globulin (ATG) on Immune Recovery after Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation.

Servais S, Menten-Dedoyart C, Beguin Y, Seidel L, Gothot A, Daulne C, Willems E, Delens L, Humblet-Baron S, Hannon M, Baron F - PLoS ONE (2015)

Lymphoid cell recovery after PBSCT with or without pre-transplant ATG-F.Levels of circulating lymphoid cells in the peripheral blood of ATG-F (blue box) and control (white box) patients are shown. Cell phenotypes were assessed for 27/34, 27/33, 27/31, 26/30, 24/30, 26/29 and 19/25 disease-free survivors in the ATG-F cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively; and for 17/23, 11/19, 10/17, 12/17, 11/17, 8/15 and 5/9 disease-free survivors in the control cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively. Box and whisker plots display the median, 25th and 75thpercentiles of the distribution (box) and whiskers extend to 5th and 95th percentiles. The grey horizontal line and shaded grey area show the median and normal range (from 5th to 95th percentile) in 22 age-matched healthy controls. *p <0.05; ** p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476691&req=5

pone.0130026.g001: Lymphoid cell recovery after PBSCT with or without pre-transplant ATG-F.Levels of circulating lymphoid cells in the peripheral blood of ATG-F (blue box) and control (white box) patients are shown. Cell phenotypes were assessed for 27/34, 27/33, 27/31, 26/30, 24/30, 26/29 and 19/25 disease-free survivors in the ATG-F cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively; and for 17/23, 11/19, 10/17, 12/17, 11/17, 8/15 and 5/9 disease-free survivors in the control cohort on days 40, 60, 80, 100, 120, 180 and 365 after PBSCT, respectively. Box and whisker plots display the median, 25th and 75thpercentiles of the distribution (box) and whiskers extend to 5th and 95th percentiles. The grey horizontal line and shaded grey area show the median and normal range (from 5th to 95th percentile) in 22 age-matched healthy controls. *p <0.05; ** p<0.01.
Mentions: Recovery of lymphoid cell subsets in the peripheral blood is shown in Fig 1A–1F. ATG-F and control patients had similar levels of circulating lymphoid cells during the first year after PBSCT, except on day 14 when they were lower in ATG-F patients. By assessing lymphoid cell subsets, we did not observe any difference in levels of NK cells (CD3-CD56+) and CD8+T cells (CD3+CD8+) between ATG-F and control patients over the first year after PBSCT, with rapid recovery of these cells in both groups (medians reaching normal values by 40–100 days after PBSCT). To the contrary, CD4+T cells (CD3+CD4+) recovered more slowly in both groups. Further, a more profound CD4+T-cell depletion was observed in ATG-F patients the first 6 months after PBSCT, mostly due to slower recovery of naive (CD3+CD4+CD45RA+) cells. Counts of memory CD4+T cells (CD3+CD4+CD45RO+) were roughly similar in both groups. Regarding B-cell (CD19+) recovery, median B-cell counts reached normal values 1 year after PBSCT in both groups. There was a trend for higher B-cell levels in ATG-F patients, although the difference reached statistical significance only on days 100 and 120 after PBSCT.

Bottom Line: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F).Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells.Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells.

View Article: PubMed Central - PubMed

Affiliation: Hematology Research Unit, GIGA-I3, University of Liège, Liège, Belgium; Bone Marrow Transplantation Unit, Department of Clinical Hematology, CHU of Liège, Liège, Belgium.

ABSTRACT

Background: Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented.

Methods: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F). Detailed phenotypes of circulating T, B, natural killer (NK) and invariant NKT (iNKT) cells were analyzed by multicolor flow cytometry at serial time-points from day 40 to day 365 after transplantation. Thymic function was also assessed by sjTREC quantification. Serious infectious events were collected up to 2 years post-transplantation.

Results: Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells. Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells. Levels of sjTRECs were similar in both cohorts at 1-year after PBSCT, suggesting that ATG-F unlikely impaired thymopoiesis at long-term after PBSCT. Finally, the incidence and rate of serious infections were similar in both groups, while ATG-F patients had a lower incidence of grade II-IV acute graft-versus-host disease.

Conclusions: Pre-transplant ATG-F induces long-lasting modulation of the circulating T-cell pool after myeloablative PBSCT, that may participate in preventing graft-versus-host disease without deeply compromising anti-pathogen defenses.

No MeSH data available.


Related in: MedlinePlus