A Cohort Study on the Association Between the Autonomic Nervous System Function and Acute GvHD After Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Conditions: Transplant-Related Disorder
Sponsor: Institute of Hematology & Blood Diseases Hospital, China

 
Clinical study protocol 
Title: 
A cohort study on the association between the autonomic nervous 
system function and acute GvHD after patients receiving allogeneic 
hematopoietic stem cell transplantation 
Portocol 
number: 
vagaGOAT-001 
Research 
unit： 
Institute of Hematology & Blood Diseases Hospital, Chinese 
Academy of Medical Sciences & Peking Union Medical College. 
Address： 
Nanjing Road, Heping district, Tianjin, China 
Version： 
2.0 
Version date： November 12, 2025 
 
 
Declaration of Secrecy 
 
This document is confidential information of Institute of Hematology & Blood Diseases Hospital, 
Chinese Academy of Medical Sciences & Peking Union Medical College (Tianjin, China) and is only 
used for the purpose of this clinical study. It shall not be disclosed to anyone other than the 
participating researchers and members of the institutional review board. This information cannot be 
used for any purpose other than the evaluation or implementation of clinical studies without the prior 
written consent of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical 
Sciences & Peking Union Medical College. 
 
 

 
 
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1. 
Research background 
At present, there are about 40,000 new allogeneic hematopoietic stem cell 
transplantation (allo-HSCT) cases every year in the world, among which about a 
quarter occur in China.1, 2 Allo-HSCT has become the primary treatment method 
for some hematological diseases such as refractory and relapsed acute leukemia 
and bone marrow failure. 
 
Evidences indicate a bidirectional interaction between the autonomic nervous 
system (ANS) and the immune system, including inflammatory responses, which 
are closely related to transplantation outcomes.3, 4 However, the role of the ANS 
in acute graft-versus-host disease (acute GvHD) in patients remains incompletely 
unclear and requires further study.  
 
Previously we have developed a dynamic forecasting model for severe acute 
GvHD, termed the ‘daGOAT model’, was constructed, achieving an AUROC 
score of more than 0.78.5 We subsequently conducted a prospective study of 
deploying daGOAT as a conditional autonomous artificial intelligence (AI) agent 
to prescribe a drug to prevent severe acute GvHD following human leukocyte 
antigen (HLA)-mismatched haematopoietic cell transplantation.6 We plan to 
utilize this model as a tool for early classification and interrogate ANS function 
of transplant recipients. 
 
1. 
Gratwohl A, Pasquini MC, Aljurf M, et al. One million haemopoietic stem-cell transplants: a 
retrospective observational study. Lancet Haematol 2015;2(3):e91-100. 
2. 
Xu LP, Wu DP, Han MZ, et al. A review of hematopoietic cell transplantation in China: data and 
trends during 2008-2016. Bone Marrow Transplant 2017;52(11):1512-18. 
3. 
Katayama Y, Battista M, Kao WM, et al. Signals from the sympathetic nervous system regulate 
hematopoietic stem cell egress from bone marrow. Cell 2006;124(2):407-21. 
4. 
Hwa YL, Shi Q, Kumar SK, et al. Beta-blockers improve survival outcomes in patients with 
multiple myeloma: a retrospective evaluation. Am J Hematol 2017;92(1):50-55. 

 
 
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5. 
Liu X, Cao Y, Guo Y, et al. Dynamic forecasting of severe acute graft-versus-host disease after 
transplantation. Nat Comput Sci 2022;2(3):153-59. 
6. 
Chen J, Cao Y, Feng Y, et al. Autonomous artificial intelligence prescribing a drug to prevent severe 
acute graft-versus-host disease in HLA-haploidentical transplants. Nat Commun 2025;16:8391. 
 
 
 

 
 
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2. 
Study design 
This is a prospective observational study. 
 
3. 
Study population 
Adult patients receiving HLA-haploidentical transplants at the Institute of 
Hematology, Chinese Academy of Medical Sciences (IHCAMS). 
 
3.1 Inclusion criteria 
1) 
Patients must be > 16 years of age; 
2) 
Patients receiving HLA-haploidentical transplants; 
3) 
Patients have to sign an informed consent form before the start of the 
research procedure. 
3.2 Exclusion criteria 
Patients who meet any of the following criteria will not be enrolled in the study: 
1) 
Tandem transplantation or multiple transplantations; 
2) 
Mental or other medical conditions that make the patients unable to comply 
with the research requirements; 
3) 
Patients who are ineligible for the study due to other factors, or will bear 
great risk if participating in the study. 
3.3 Drop-out and withdrawal criteria 
A patient may withdraw from the study if he/she does not wish to continue 
participating in the study, and the date and reason for withdrawal shall be 
recorded. The investigator may also decide to discontinue a patient from the 
clinical study if there is an unacceptable risk. 
 
4. 
Trial Protocol 
During days 17 to 23 posttransplant, the daGOAT model will be used for 
dynamic risk prediction and stratification. Autonomic nervous system functional 
tests including heart rate response to standing, piloerection, and dynamic 

 
 
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electrocardiography will be performed on patients before transplantation and 
during 17 to 25 days after transplantation. 
 
5. 
Sample collection and omics analysis  
Blood and bone marrow samples will be collected from patients for analyses with 
the aim to further improve the daGOAT predictive model and facilitate molecular 
biological investigations. 
 
6. 
Study assessment and follow-up 
7.1 Medical history 
Medical history (previous treatments, including chemotherapy). 
7.2 Physical examination 
Physical examination before transplantation, including body height, body 
weight, body surface area, and the Eastern Cooperative Oncology Group score. 
7.3 Laboratory tests  
Laboratory tests performed at diagnosis and before and after transplantation. 
7.4 Follow-up. 
Patients will be followed up after transplantation; data on infection, relapse, 
survival, and quality of life will be collected. 
 
7. 
Study endpoints 
8.1  Primary endpoint 
Autonomous nervous system functional test results.  
8.2  Secondary endpoints 
Incidence of severe acute GvHD after transplantation within 100 days and 
incidences of acute GvHD (any grade) in various target organs. 
 

 
 
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8. 
Sample size calculation 
60 adult patients receiving allo-HSCT. 
 
9. 
Statistical analysis 
R statistical analysis software will be used to conduct the statistical analysis 
tailored to data properties. All comparison tests will be two-sided, and statistical 
significance will be defined as P < 0.05 in all the analyses. 
 
10. Ethical review 
The study will be conducted in accordance with the Declaration of Helsinki 
(2024), relevant regulations issued by the government of the People’s Republic 
of China, and additional precautions required by the ethics review committee at 
the IHCAMS. 
Before the study, the investigator will obtain approvals from the Ethics Review 
committee at the IHCAMS regarding the study protocol data sheet, informed 
consent form, subject enrollment form, and other relevant information to be 
provided to the subject before enrollment. During the study, if there is any 
amendment to the study protocol data sheet, informed consent form, subject 
enrollment form, or other relevant information provided to subjects, renewed 
approvals shall be obtained from the IHCAMS Ethics Review committee before 
continuation of the study. 
 
11. Preservation of research data 
All data of this study will be stored at the IHCAMS. Data sharing among the 
researchers will abide by the regulations of the People’s Republic of China to 
safeguard data security and subject privacy.