CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

Frederick L Locke; Joseph Pidala; Barry Storer; Paul J Martin; Michael A Pulsipher; Thomas R Chauncey; Niels Jacobsen; Nicolaus Kröger; Irwin Walker; Susan Light; Bronwen E Shaw; Francisca Beato; Ginna G Laport; Auayporn Nademanee; Armand Keating; Gerard Socie; Claudio Anasetti

doi:10.1016/j.bbmt.2016.12.624

CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

Standard

CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation. / Locke, Frederick L; Pidala, Joseph; Storer, Barry; Martin, Paul J; Pulsipher, Michael A; Chauncey, Thomas R; Jacobsen, Niels; Kröger, Nicolaus; Walker, Irwin; Light, Susan; Shaw, Bronwen E; Beato, Francisca; Laport, Ginna G; Nademanee, Auayporn; Keating, Armand; Socie, Gerard; Anasetti, Claudio.

in: BIOL BLOOD MARROW TR, Jahrgang 23, Nr. 3, 03.2017, S. 405-411.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Locke, FL, Pidala, J, Storer, B, Martin, PJ, Pulsipher, MA, Chauncey, TR, Jacobsen, N, Kröger, N, Walker, I, Light, S, Shaw, BE, Beato, F, Laport, GG, Nademanee, A, Keating, A, Socie, G & Anasetti, C 2017, 'CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation', BIOL BLOOD MARROW TR, Jg. 23, Nr. 3, S. 405-411. https://doi.org/10.1016/j.bbmt.2016.12.624

APA

Locke, F. L., Pidala, J., Storer, B., Martin, P. J., Pulsipher, M. A., Chauncey, T. R., Jacobsen, N., Kröger, N., Walker, I., Light, S., Shaw, B. E., Beato, F., Laport, G. G., Nademanee, A., Keating, A., Socie, G., & Anasetti, C. (2017). CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation. BIOL BLOOD MARROW TR, 23(3), 405-411. https://doi.org/10.1016/j.bbmt.2016.12.624

Vancouver

Locke FL, Pidala J, Storer B, Martin PJ, Pulsipher MA, Chauncey TR et al. CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation. BIOL BLOOD MARROW TR. 2017 Mär;23(3):405-411. https://doi.org/10.1016/j.bbmt.2016.12.624

Bibtex

@article{a9754e51c60b4d59809722211bab3031,

title = "CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation",

abstract = "Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25(+)FOXP3(+) regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0.3 mg/kg (n = 69) or 1.2 mg/kg (n = 76) or placebo (n = 65) after unrelated marrow transplantation for treatment of hematologic malignancies or severe aplastic anemia. The risk of acute GVHD did not differ among the groups (P = .68). Long-term follow-up of clinical outcomes and correlative analysis of peripheral blood T cell phenotype suggested that the patients treated with daclizumab had an increased risk of chronic GVHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.0 to 2.3; P = .08) and a decreased risk of relapse (HR, 0.57; 95% CI, 0.3 to 1.0; P = .05), but similar survival (HR, 0.89; 95% CI, 0.6 to 1.3; P = .53). T cells from a subset of patients (n = 107) were analyzed by flow cytometry. Compared with placebo, treatment with daclizumab decreased the proportion of Tregs among CD4 T cells at days 11-35 and increased the proportion of central memory cells among CD4 T cells at 1 year. Prophylactic administration of daclizumab does not prevent acute GVHD, but may increase the risk of chronic GVHD and decrease the risk of relapse. By delaying Treg reconstitution and promoting immunologic memory, anti-CD25 therapy may augment alloreactivity and antitumor immunity.",

keywords = "Journal Article",

author = "Locke, {Frederick L} and Joseph Pidala and Barry Storer and Martin, {Paul J} and Pulsipher, {Michael A} and Chauncey, {Thomas R} and Niels Jacobsen and Nicolaus Kr{\"o}ger and Irwin Walker and Susan Light and Shaw, {Bronwen E} and Francisca Beato and Laport, {Ginna G} and Auayporn Nademanee and Armand Keating and Gerard Socie and Claudio Anasetti",

note = "Copyright {\textcopyright} 2017. Published by Elsevier Inc.",

year = "2017",

month = mar,

doi = "10.1016/j.bbmt.2016.12.624",

language = "English",

volume = "23",

pages = "405--411",

journal = "BIOL BLOOD MARROW TR",

issn = "1083-8791",

publisher = "Elsevier Inc.",

number = "3",

}

RIS

TY - JOUR

T1 - CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

AU - Locke, Frederick L

AU - Pidala, Joseph

AU - Storer, Barry

AU - Martin, Paul J

AU - Pulsipher, Michael A

AU - Chauncey, Thomas R

AU - Jacobsen, Niels

AU - Kröger, Nicolaus

AU - Walker, Irwin

AU - Light, Susan

AU - Shaw, Bronwen E

AU - Beato, Francisca

AU - Laport, Ginna G

AU - Nademanee, Auayporn

AU - Keating, Armand

AU - Socie, Gerard

AU - Anasetti, Claudio

PY - 2017/3

Y1 - 2017/3

N2 - Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25(+)FOXP3(+) regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0.3 mg/kg (n = 69) or 1.2 mg/kg (n = 76) or placebo (n = 65) after unrelated marrow transplantation for treatment of hematologic malignancies or severe aplastic anemia. The risk of acute GVHD did not differ among the groups (P = .68). Long-term follow-up of clinical outcomes and correlative analysis of peripheral blood T cell phenotype suggested that the patients treated with daclizumab had an increased risk of chronic GVHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.0 to 2.3; P = .08) and a decreased risk of relapse (HR, 0.57; 95% CI, 0.3 to 1.0; P = .05), but similar survival (HR, 0.89; 95% CI, 0.6 to 1.3; P = .53). T cells from a subset of patients (n = 107) were analyzed by flow cytometry. Compared with placebo, treatment with daclizumab decreased the proportion of Tregs among CD4 T cells at days 11-35 and increased the proportion of central memory cells among CD4 T cells at 1 year. Prophylactic administration of daclizumab does not prevent acute GVHD, but may increase the risk of chronic GVHD and decrease the risk of relapse. By delaying Treg reconstitution and promoting immunologic memory, anti-CD25 therapy may augment alloreactivity and antitumor immunity.

AB - Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25(+)FOXP3(+) regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0.3 mg/kg (n = 69) or 1.2 mg/kg (n = 76) or placebo (n = 65) after unrelated marrow transplantation for treatment of hematologic malignancies or severe aplastic anemia. The risk of acute GVHD did not differ among the groups (P = .68). Long-term follow-up of clinical outcomes and correlative analysis of peripheral blood T cell phenotype suggested that the patients treated with daclizumab had an increased risk of chronic GVHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.0 to 2.3; P = .08) and a decreased risk of relapse (HR, 0.57; 95% CI, 0.3 to 1.0; P = .05), but similar survival (HR, 0.89; 95% CI, 0.6 to 1.3; P = .53). T cells from a subset of patients (n = 107) were analyzed by flow cytometry. Compared with placebo, treatment with daclizumab decreased the proportion of Tregs among CD4 T cells at days 11-35 and increased the proportion of central memory cells among CD4 T cells at 1 year. Prophylactic administration of daclizumab does not prevent acute GVHD, but may increase the risk of chronic GVHD and decrease the risk of relapse. By delaying Treg reconstitution and promoting immunologic memory, anti-CD25 therapy may augment alloreactivity and antitumor immunity.

KW - Journal Article

U2 - 10.1016/j.bbmt.2016.12.624

DO - 10.1016/j.bbmt.2016.12.624

M3 - SCORING: Journal article

C2 - 28007665

VL - 23

SP - 405

EP - 411

JO - BIOL BLOOD MARROW TR

JF - BIOL BLOOD MARROW TR

SN - 1083-8791

IS - 3

ER -