This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sutherland, J. S. Articles by Boyd, R. L. Search for Related Content PubMed PubMed Citation Articles by Sutherland, J. S. Articles by Boyd, R. L.

Enhanced Immune System Regeneration in Humans Following Allogeneic or Autologous Hemopoietic Stem Cell Transplantation by Temporary Sex Steroid Blockade

Authors' Affiliations: ¹ Department of Immunology, Monash University, Clayton, Victoria, Australia, ² Bone Marrow Transplant Programme, The Alfred Hospital, ³ The Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia, and ⁴ The Anthony Nolan Research Institute, Hampstead, London, England

Requests for reprints: Richard Boyd, Monash Immunology and Stem Cell Laboratories, Clayton, Victoria 3800, Australia. E-mail: Richard.Boyd{at}med.monash.edu.au.

Purpose: To determine if temporarily blocking sex steroids prior to stem cell transplantation can increase thymus function and thus enhance the rate of T cell regeneration.

Experimental Design: This was a pilot study of luteinizing hormone–releasing hormone agonist (LHRH-A) goserelin given 3 weeks prior to allogeneic or autologous hemopoietic stem cell transplantation and administered up to 3 months posttransplantation. Patients (with or without LHRH-A administration) were assessed from 1 week to 12 months posttransplantation for multiple immunologic variables by flow cytometry (particularly naïve T cells), quantitative PCR to assess T-cell receptor excision circle levels (as a correlate of thymus function), CDR3 length analysis to determine the variability of the TCR repertoire, and in vitro assays to determine functional T cell responses.

Results: LHRH-A administration prior to stem cell transplantation significantly increased neutrophil and lymphocyte numbers within the first month of posttransplantation. Most importantly, total and naïve CD4⁺ T cell regeneration together with T-cell receptor excision circle production, T cell repertoire regeneration, and peripheral T cell function were also significantly enhanced at multiple time points posttransplant. In addition, an increase in disease-free survival (P = 0.04) was seen in the autologous setting. Although LHRH-A administration increased T cell responses in vitro, it did not exacerbate graft-versus-host disease in the allogeneic setting.

Conclusions: This study provides an important new approach to the improvement of immune reconstitution in patients undergoing hemopoietic stem cell transplantation and may have generic applications in many T cell–based disorders.

This article has been cited by other articles:

				E. Clave, M. Busson, C. Douay, R. Peffault de Latour, J. Berrou, C. Rabian, M. Carmagnat, V. Rocha, D. Charron, G. Socie, et al. Acute graft-versus-host disease transiently impairs thymic output in young patients after allogeneic hematopoietic stem cell transplantation Blood, June 18, 2009; 113(25): 6477 - 6484. [Abstract] [Full Text] [PDF]

				G. L. Goldberg, C. G. King, R. A. Nejat, D. Y. Suh, O. M. Smith, J. C. Bretz, R. M. Samstein, J. A. Dudakov, A. P. Chidgey, S. Chen-Kiang, et al. Luteinizing Hormone-Releasing Hormone Enhances T Cell Recovery following Allogeneic Bone Marrow Transplantation J. Immunol., May 1, 2009; 182(9): 5846 - 5854. [Abstract] [Full Text] [PDF]

				A. L. Fletcher, N. Seach, J. J. Reiseger, T. E. Lowen, M. V. Hammett, H. S. Scott, and R. L. Boyd Reduced Thymic Aire Expression and Abnormal NF-{kappa}B2 Signaling in a Model of Systemic Autoimmunity J. Immunol., March 1, 2009; 182(5): 2690 - 2699. [Abstract] [Full Text] [PDF]

				R. R. Jenq, C. G. King, C. Volk, D. Suh, O. M. Smith, U. K. Rao, N. L. Yim, A. M. Holland, S. X. Lu, J. L. Zakrzewski, et al. Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation Blood, February 12, 2009; 113(7): 1574 - 1580. [Abstract] [Full Text] [PDF]

				A. L. Barnard, A. P. Chidgey, C. C. Bernard, and R. L. Boyd Androgen depletion increases the efficacy of bone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis Blood, January 1, 2009; 113(1): 204 - 213. [Abstract] [Full Text] [PDF]

				K. M. Williams, P. J. Lucas, C. V. Bare, J. Wang, Y.-W. Chu, E. Tayler, V. Kapoor, and R. E. Gress CCL25 increases thymopoiesis after androgen withdrawal Blood, October 15, 2008; 112(8): 3255 - 3263. [Abstract] [Full Text] [PDF]