Umbilical cord blood-derived T regulatory cells to prevent GVHD: Kinetics, toxicity profile, and clinical effect

Claudio G. Brunstein; Jeffrey S. Miller; David H. McKenna; Keli L. Hippen; Todd E. DeFor; Darin Sumstad; Julie Curtsinger; Michael R. Verneris; Margaret L. MacMillan; Bruce L. Levine; James L. Riley; Carl H. June; Chap Le; Daniel J. Weisdorf; Philip B. McGlave; Bruce R. Blazar; John E. Wagner

doi:10.1182/blood-2015-06-653667

Umbilical cord blood-derived T regulatory cells to prevent GVHD: Kinetics, toxicity profile, and clinical effect

Claudio G. Brunstein, Jeffrey S. Miller, David H. McKenna, Keli L. Hippen, Todd E. DeFor, Darin Sumstad, Julie Curtsinger, Michael R. Verneris, Margaret L. MacMillan, Bruce L. Levine, James L. Riley, Carl H. June, Chap Le, Daniel J. Weisdorf, Philip B. McGlave, Bruce R. Blazar, John E. Wagner

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311 Scopus citations

Abstract

We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 × 10⁶ Treg/kg. The median proportion of CD4⁺FoxP3⁺CD127^- in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n 5 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P 5 .05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and diseasefree survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD.

Original language	English (US)
Pages (from-to)	1044-1051
Number of pages	8
Journal	Blood
Volume	127
Issue number	8
DOIs	https://doi.org/10.1182/blood-2015-06-653667
State	Published - Feb 25 2016

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Publisher Copyright:
© 2016 by The American Society of Hematology.

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Brunstein, C. G., Miller, J. S., McKenna, D. H., Hippen, K. L., DeFor, T. E., Sumstad, D., Curtsinger, J., Verneris, M. R., MacMillan, M. L., Levine, B. L., Riley, J. L., June, C. H., Le, C., Weisdorf, D. J., McGlave, P. B., Blazar, B. R., & Wagner, J. E. (2016). Umbilical cord blood-derived T regulatory cells to prevent GVHD: Kinetics, toxicity profile, and clinical effect. Blood, 127(8), 1044-1051. https://doi.org/10.1182/blood-2015-06-653667

Brunstein, CG, Miller, JS , McKenna, DH , Hippen, KL , DeFor, TE, Sumstad, D, Curtsinger, J, Verneris, MR, MacMillan, ML, Levine, BL, Riley, JL, June, CH, Le, C, Weisdorf, DJ, McGlave, PB, Blazar, BR & Wagner, JE 2016, 'Umbilical cord blood-derived T regulatory cells to prevent GVHD: Kinetics, toxicity profile, and clinical effect', Blood, vol. 127, no. 8, pp. 1044-1051. https://doi.org/10.1182/blood-2015-06-653667

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AU - Curtsinger, Julie

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AU - Riley, James L.

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Umbilical cord blood-derived T regulatory cells to prevent GVHD: Kinetics, toxicity profile, and clinical effect

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