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


CONCLUSIONS
The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes.
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, Beijing, China.|Department of Hematology, 309th Hospital, Chinese People's Liberation Army, Beijing, China.
Deng-Mei
DM
Tian
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, Beijing, China.
Yu
Y
Wang
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, Beijing, China.
Xiao-Hui
XH
Zhang
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, Beijing, China.
Kai-Yan
KY
Liu
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.|Collabrative Innovation Center of Hematology, Peking University, Beijing, China.
Xiao-Jun
XJ
Huang
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, Beijing, China.|Collabrative Innovation Center of Hematology, Peking University, Beijing, China.
Ying-Jun
YJ
Chang
D000293:Adolescent; D000328:Adult; D064591:Allografts; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D020127:Recovery of Function; D015996:Survival Rate; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism