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Clinical Trial
. 2016 Jun 8;11(6):e0156777.
doi: 10.1371/journal.pone.0156777. eCollection 2016.

Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation

Deng-Mei Tian  1   2 , Yu Wang  1 , Xiao-Hui Zhang  1 , Kai-Yan Liu  1 , Xiao-Jun Huang  1   3   4 , Ying-Jun Chang  1   4
Affiliations
Clinical Trial

Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation

Deng-Mei Tian et al. PLoS One. .

Abstract

Background: Rapid immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is significantly associated with lower infection, relapse and possibly secondary malignancy rates. The aim of this study was to investigate the role of peripheral lymphocyte subsets, especially CD3+CD8+ cytotoxic T cell recovery, in predicting transplant outcomes, including the overall survival (OS) and non-relapse mortality (NRM) rates after unmanipulated haploidentical blood and marrow transplantation (HBMT).

Methods: Peripheral blood samples were obtained from 214 HBMT recipients with hematological malignancies. The peripheral lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, and CD19+ B cells) were analyzed by flow cytometry at days 30, 60, 90, 180, 270 and 360 after HBMT.

Results: The CD3+CD8+ cytotoxic T cell recovery at day 90 (CD3+CD8+-90) was correlated with bacterial infection (P = 0.001), NRM (P = 0.001), leukemia-free survival (LFS, P = 0.005), and OS (P = 0.001) at a cutoff value of 375 cells/μL CD3+CD8+ T cells. The incidence of bacterial infection in patients with the CD3+CD8+-90 at ≥375 cells/μL was significantly lower than that of cases with the CD3+CD8+-90 at <375 cells/μL after HBMT (14.6% versus 41.6%, P<0.001). Multivariate analysis showed the rapid recovery of CD3+CD8+ T cells at day 90 after HBMT was strongly associated with a lower incidence of NRM (HR = 0.30; 95% CI: 0.15-0.60; P = 0.000) and superior LFS (HR = 0.51; 95% CI: 0.32-0.82; P = 0.005) and OS (HR = 0.38; 95% CI: 0.23-0.63; P = 0.000).

Conclusion: The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Lymphocyte subset recovery after unmanipulated HBMT.
The median of each lymphocyte subset gradually rose on days 30, 60, 90, 180, 270, and 360 post-transplant, and included: (A) CD3+ T cells; (B) CD3+CD4+ helper T cells; (C) CD3+CD8+ cytotoxic T cells; and (D) CD19+ B cells. (E) Differences in the CD3+CD8+-90 T cell recovery for patients with CD3+CD8+-90 ≥375 cells/μL and those with CD3+CD8+-90 <375 cells/μL and (F) differences in the CD3+CD8+-90 T cell recovery for standard-risk and high-risk patients are shown. *P<0.05, **P<0.01.
Fig 2
Fig 2. The impact of the CD3+CD8+ T cell recovery after unmanipulated HBMT on subsequent immune recovery, until day 360.
(A) Correlation between the CD3+CD8+ T-cell recovery at days 90 and 180; (B) Correlation between the CD3+CD8+ T-cell recovery at days 90 and 270; (C) Correlation between the CD3+CD8+ T-cell recovery at days 90 and 360. The r-value represents the Spearman’s rank correlation coefficient; P value represents the significance of the correlation.
Fig 3
Fig 3. The impact of the CD3+CD8+-90 T cell recovery after unmanipulated HBMT on transplantation outcome.
(A) Cumulative incidence of non-relapse mortality; (B) cumulative incidence of relapse; (C) leukemia-free survival; (D) overall survival rates, according to CD3+CD8+-90 T cell counts at days 90.
See this image and copyright information in PMC

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