Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade.
Clin Cancer Res
; 14(4): 1138-49, 2008 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-18281548
ABSTRACT
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. EXPERIMENTALDESIGN:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Goserelin
/
Hematopoietic Stem Cell Transplantation
/
Antineoplastic Agents, Hormonal
/
Hematologic Neoplasms
/
Transplantation Conditioning
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2008
Type:
Article
Affiliation country:
Australia