T cell reconstitution in allogeneic haematopoietic stem cell transplantation: prognostic significance of plasma interleukin-7
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T cell reconstitution in allogeneic haematopoietic stem cell transplantation : prognostic significance of plasma interleukin-7. / Kielsen, K; Jordan, K K; Uhlving, H H; Pontoppidan, P L; Shamim, Z; Ifversen, M; Heilmann, C; Nielsen, C H; Sengeløv, H; Ryder, L P; Müller, K G.
In: Scandinavian Journal of Immunology, Vol. 81, No. 1, 01.2015, p. 72-80.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - T cell reconstitution in allogeneic haematopoietic stem cell transplantation
T2 - prognostic significance of plasma interleukin-7
AU - Kielsen, K
AU - Jordan, K K
AU - Uhlving, H H
AU - Pontoppidan, P L
AU - Shamim, Z
AU - Ifversen, M
AU - Heilmann, C
AU - Nielsen, C H
AU - Sengeløv, H
AU - Ryder, L P
AU - Müller, K G
N1 - © 2014 John Wiley & Sons Ltd.
PY - 2015/1
Y1 - 2015/1
N2 - Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4(+) : β = -2.1 × 10(6) cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.
AB - Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4(+) : β = -2.1 × 10(6) cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.
KW - Adolescent
KW - Adult
KW - Bone Marrow Diseases
KW - CD4 Lymphocyte Count
KW - CD4-Positive T-Lymphocytes
KW - CD8-Positive T-Lymphocytes
KW - Child
KW - Child, Preschool
KW - Female
KW - Graft vs Host Disease
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Infant
KW - Interleukin-7
KW - Lymphopenia
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Prospective Studies
KW - Transplantation Conditioning
KW - Transplantation, Homologous
KW - Young Adult
U2 - 10.1111/sji.12244
DO - 10.1111/sji.12244
M3 - Journal article
C2 - 25263171
VL - 81
SP - 72
EP - 80
JO - Scandinavian Journal of Immunology, Supplement
JF - Scandinavian Journal of Immunology, Supplement
SN - 0301-6323
IS - 1
ER -
ID: 162415064