Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade.
OBJECTIVE
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.


METHODS
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.
Sutherland
Jayne S
JS
Department of Immunology, Monash University, Clayton, Victoria, Australia.
Spyroglou
Lisa
L
Muirhead
Jennifer L
JL
Heng
Tracy S
TS
Prieto-Hinojosa
Adria
A
Prince
H Miles
HM
Chidgey
Ann P
AP
Schwarer
Anthony P
AP
Boyd
Richard L
RL
D000293:Adolescent; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005434:Flow Cytometry; D017273:Goserelin / Q000627:therapeutic use*; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects*; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D018931:Antineoplastic Agents, Hormonal; D011948:Receptors, Antigen, T-Cell; D017273:Goserelin