Pre-transplantation thymic function is associated with the risk of acute graft versus host disease and cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

ABSTRACT

Objectives: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT.

Methods: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled. Periphery blood samples were collected before conditioning and at 1, 2, 3 months after AHSCT. T-cell subsets were analyzed with flow cytometry. Genomic DNA was purified from peripheral blood mononuclear cells (PBMCs), and sjTREC was quantified by real-time PCR. Impact of sjTREC and CD31 + RTE on aGVHD and CMV viremia was evaluated by univariate and multivariate Cox regression analyses.

Results: The analyzed T-cell subsets and sjTREC of patients before AHSCT were all significantly lower than those of healthy donors (p < 0.05). sjTREC and CD31 + RTE were remarkably decreased in 3 months after AHSCT (p < 0.05). Patients with lower pre-transplantation sjTREC and CD31 + RTE level had higher incidence of CMV viremia after AHSCT (p < 0.05). sjTREC/10⁶ PBMCs was negatively correlated with aGVHD (p = 0.024).

Conclusion: Thymic function was impaired before transplantation, and was consistently decreased in 3 months after AHSCT. Patients who had lower pre-transplantation sjTREC level were at high risk of aGVHD and CMV viremia after AHSCT, low pre-transplantation CD31 + RTE was correlated with CMV viremia after AHSCT.

KEYWORDS:

• Thymic function
• signal joint TCR rearrangement excision circle
• CD31-positive recent thymic emigrant
• acute graft versus host disease
• cytomegalovirus viremia

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Xin Yang is an MD, PhD student, Peking Union Medical College and Chinese Academy of Medical Sciences.

Yuanxin Sun is an MD, PhD student, Shandong University.

Sudong Zhang is an MD, PhD student, Peking Union Medical College and Chinese Academy of Medical Sciences.

Hui Yang is an MD, PhD student, Shandong University.

Jialin Wei is an MD, PhD, associate chief physician, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.

Yi He is an MD, PhD, associate chief physician, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.

Donglin Yang is an MD, PhD, associate chief physician, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.

Erlie Jiang is an MD, PhD, associate chief physician, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.

Mingzhe Han is an MD, PhD, chief physician, director of Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.

Xuemei Qin is an MD, PhD, associate chief physician, Department of Hematology, Qilu Hospital, Shandong University.

Sizhou Feng is an MD, PhD, chief physician, the vice director of Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences.

ORCID

Xin Yang http://orcid.org/0000-0002-7343-8412

Donglin Yang http://orcid.org/0000-0003-4056-4743

Additional information

Funding

This work was supported by the Department of Science & Technology of Shandong province under Grant 2013GGE27049, Chinese Medical Association under Grant 16010130629, and Chinese Academy of Medical Sciences & Peking Union Medical College under Grant 2016-12M-1-017.