Clinical trial NCT03727230: RhD+ Blood Transfusion to Asian-type DEL Recipients
Official title: Single-arm Multicenter Clinical Trial of Blood Transfusion From RhD+ Donors to Asian-type DEL Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Transfusion
Rhesus Isoimmunisation Due to Anti-D
Blood Group Antigen Abnormality
Lead sponsor: Guangzhou Blood Center
Sponsor class: OTHER_GOV
Collaborators: name: Sun Yat-sen University
name: Southern Medical University, China
name: Guangdong Provincial People's Hospital
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Zhujiang Hospital
name: Second Affiliated Hospital of Guangzhou Medical University
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
name: Guangdong Second Provincial General Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: Guangdong Provincial Institute of Biological Products And Materia Medica
name: Shenzhen Second People's Hospital
name: Koo Foundation Sun Yat-Sen Cancer Center
First posted: 2018-11-01
Enrollment: 54
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single-arm clinical trial of Chinese Asian-type DEL patients receiving RhD+ RBC transfusion was conducted.

Although truly RhD-negative patients receiving RhD+ RBC transfusion were recognized as the ideal control group, they were not included in this study because it did not comply with the Chinese Clinical Blood Transfusion Standard and ethics principles. The truly RhD-negative patients could receive RhD+ blood only in emergency situations under conditions of an insufficient stock of RhD-negative RBCs. Thus, the summarized alloanti-D rate (203/720, 28.2%; 95% CI, 19%-32%) in truly RhD-negative patients with similar mixed diseases after RhD+ RBC transfusion reported in the meta-analysis （Vox Sang 2021, http://doi.org/10.1111/vox.13232）was used as the control for comparison.
Primary purpose: TREATMENT

Brief summary: Red blood cells (RBCs) from Asian-type DEL blood group express very weak RhD antigen and are falsely typed as RhD-negative blood group in routine RhD testing. Until now, Asian-type DEL (D-eluate) patients still be treated as rare RhD-negative patients in the clinic. Previous study from the Asian-type DEL pregnant women with RhD+ fetus showed no occurrence of alloanti-D immunization. This result, however, does not directly be applied for Asian-type DEL patients receiving RhD+ blood transfusions, as lacking of direct evidence regarding the safety and underlying mechanism.

In this study, the patients with Asian-type DEL were identified and received RhD+ blood transfusion, then evaluations of any adverse reactions, especially the active follow-up alloantibody test, were prospectively conducted.

Detailed description: Red blood cells (RBCs) from Asian-type DEL individuals express very weak RhD antigen and are falsely typed as RhD-negative in routine RhD testing. Recent studies have shown that 9-30% of individuals with a serologically apparent RhD-negative phenotype in East and Southeast Asian populations, including Chinese, Korean, Japanese, Thai and Myanmar, actually are not truly RhD-negative but exhibit the DEL (D-eluate) phenotype, which represents almost 1.7 million Asian-type DEL individuals in China, 250,000 in Korea, Japan, Thailand, and Myanmar as well as at least 90,000 in the US among Asian immigrants. Nowadays, Asian-type DEL patients are conventionally transfused with RhD-negative RBC, which are difficult to organize because of the undersupply of the rare RhD-negative blood in these Asian countries, due to low frequency distribution (0.3-0.4%).

However, our previous study demonstrated that Asian-type DEL pregnant women with RhD+ fetus did not develop alloanti-D during the pregnancy. Latter, this phenomenon was confirmed by different medical centers in China. Accordingly, Asian-type DEL patients may also not be able to produce alloanti-D after transfusion with RhD+ RBC and consequently the use of RhD-negative RBCs for the transfusion management of Asian-type patients may be superfluous. However, this hypothesis needs to be carefully proved.

In this study, we were able to verify this assumption. Blood samples from 2,011 Chinese patients with a primary RhD-negative phenotype from the hospitals in Guangzhou of China were typed for Asian-type DEL blood group in the Guangzhou Blood Center. DEL phenotyping was performed by the serological adsorption/elution antibody testing and genotyping for the Asian-type DEL specific allele (RHD\*1227A) detection was conducted using a well validated high-resolution melting (HRM) approach. Then, transfusions of RhD+ RBC were performed in a cohort of Asian-type DEL patients. After RhD+ blood transfusion, evaluations of any adverse reactions, especially the active follow-up alloantibody test, were conducted to evaluate the alloanti-D immunization. Besides, effectiveness of transfusion (Hb changes) was also recorded.

Eligibility criteria: Inclusion criteria for eligible participants were as follows: (1) Asian-type DEL blood group; (2) male patients, or female patients ≥ 49 years of age, or female with severe illness and no plan for further pregnancy; (3) needing blood transfusion in line with guidelines for internal medicine or surgery; and (4) signed voluntary informed consent for blood transfusion treatment before the trial.

The exclusion criteria were: (1) adverse reaction in a previous transfusion; (2) allergies to blood products or immunodeficiency diseases; (3) needing massive blood transfusion for acute blood loss; (4) positive pregnancy test results; (5) conscious dysfunction or severe mental illness; and (6) unsuitability for the study, as estimated by the principal investigators.

Primary outcomes:
measure: Occurrence of Alloanti-D Immunization in Asian-type DEL Recipients Transfused With RhD+ RBCs
timeFrame: A median follow-up of 226 days (range, 32 to 1354 days) after RhD+ RBC transfusion
Secondary outcomes:
measure: Adverse Transfusion Reaction Analysis in Asian-type DEL Recipients During or After RhD+ Blood Transfusion
timeFrame: During the blood transfusion and in the days of hospitalization
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Province Traditional Chinese Medical Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Second Provincial General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou University of Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Blood Center
state: Guangdong
Study officials:
affiliation: Guangzhou Blood Center
name: Yongshui Fu, MD, PhD
role: STUDY_CHAIR
References: