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Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

Publication ,  Journal Article
Nash, RA; Dansey, R; Storek, J; Georges, GE; Bowen, JD; Holmberg, LA; Kraft, GH; Mayes, MD; McDonagh, KT; Chen, C-S; Dipersio, J; Pavletic, S ...
Published in: Biol Blood Marrow Transplant
September 2003

High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited, the time course and similarity of the 2 cases of EBV-PTLD and the effect on day 28 T-cell counts support a relationship between the development of EBV-PTLD and the administration of rabbit ATG. The differences between equine and rabbit ATG are not yet clearly defined, and they should not be considered interchangeable in this regimen without further study.

Duke Scholars

Published In

Biol Blood Marrow Transplant

DOI

ISSN

1083-8791

Publication Date

September 2003

Volume

9

Issue

9

Start / End Page

583 / 591

Location

United States

Related Subject Headings

  • Transplantation, Autologous
  • Transplantation Conditioning
  • T-Lymphocytes
  • Scleroderma, Systemic
  • Rabbits
  • Platelet Transfusion
  • Peripheral Blood Stem Cell Transplantation
  • Opportunistic Infections
  • Neutrophils
  • Multiple Sclerosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nash, R. A., Dansey, R., Storek, J., Georges, G. E., Bowen, J. D., Holmberg, L. A., … McSweeney, P. A. (2003). Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases. Biol Blood Marrow Transplant, 9(9), 583–591. https://doi.org/10.1016/s1083-8791(03)00228-3
Nash, Richard A., Roger Dansey, Jan Storek, George E. Georges, James D. Bowen, Leona A. Holmberg, George H. Kraft, et al. “Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.Biol Blood Marrow Transplant 9, no. 9 (September 2003): 583–91. https://doi.org/10.1016/s1083-8791(03)00228-3.
Nash RA, Dansey R, Storek J, Georges GE, Bowen JD, Holmberg LA, Kraft GH, Mayes MD, McDonagh KT, Chen C-S, Dipersio J, Lemaistre CF, Pavletic S, Sullivan KM, Sunderhaus J, Furst DE, McSweeney PA. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases. Biol Blood Marrow Transplant. 2003 Sep;9(9):583–591.
Journal cover image

Published In

Biol Blood Marrow Transplant

DOI

ISSN

1083-8791

Publication Date

September 2003

Volume

9

Issue

9

Start / End Page

583 / 591

Location

United States

Related Subject Headings

  • Transplantation, Autologous
  • Transplantation Conditioning
  • T-Lymphocytes
  • Scleroderma, Systemic
  • Rabbits
  • Platelet Transfusion
  • Peripheral Blood Stem Cell Transplantation
  • Opportunistic Infections
  • Neutrophils
  • Multiple Sclerosis