Journal List > Immune Netw > v.18(2) > 1108144

Bae, Jung, Kim, Kang, Lee, Chong, Sung, Lee, Choi, Kim, Woo, Lee, Lee, Lee, and Kim: The Detailed Kinetics of Cytomegalovirus-specific T cell Responses after Hematopoietic Stem Cell Transplantation: 1 Year Follow-up Data

Abstract

The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.

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Figure 1.
Kinetics of (A) pp65- and (B) IE1-specific ELISPOT assays over the first year after transplantation in hematopoietic stem cell recipients. Bars indicate median values. Only significant p-values are shown. PBMC, peripheral blood mononuclear cell. * p<0.05.
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Figure 2.
Four patterns of immune reconstitution in hematopoietic stem cell recipients. (A) Spontaneous recovery without CMV infection. (B) T cell reconstitution with a preceding CMV infection. (C) Failure of gradual or sustained T cell reconstitution. (D) Absence of T cell reconstitution. PBMC, peripheral blood mononuclear cell.
in-18-e2f2.tif
Table 1.
Baseline demographic and clinical characteristics of 51 recipients of HCTs
Characteristic Total (n=51)
Median age (range, yr) 41 (20–64)
Male 32 (63)
Underlying disease  
   Acute myeloid leukemia 32 (63)
   Myelodysplastic syndrome 8 (16)
   Aplastic anemia 6 (12)
   Acute lymphocytic leukemia 2 (4)
   Chronic myeloid leukemia 1 (2)
   Non-Hodgkin's lymphoma 1 (2)
   Hemophagocytic lymphohistiocytosis 1 (2)
Transplant type  
   Full allogeneic 10 (20)
   Non-myeloablative allogeneic 41 (80)
Stem cell source  
   Peripheral blood 51 (100)
   Cord blood or bone marrow 0 (0)
HLA matching  
   Matched related 19 (37)
   Matched unrelated 16 (31)
   Mismatched related 13 (25)
   Mismatched unrelated 3 (6)
CMV serostatus  
   Donor positive/recipient positive 51 (100)
Remission before HCT 27 (53)
Acute GVHD 13 (25)
Chronic GVHD 13 (25)
Preemptive ganciclovir therapy 17 (33)
Corticosteroid use before HCT 11 (22)
Corticosteroid use after HCT 46 (90)
GVHD prophylaxis regimen  
   Cyclosporine 51 (100)
   Methotrexate 43 (84)
   Tacrolimus or mycophenolate 7 (14)
CMV infection 26 (51)
Relapsing CMV infection 10 (20)
CMV disease 3 (6)

Values are number (%) unless otherwise indicated.

HLA, human leukocyte antigen.

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