Kinectics of Donor-specific Anti-HLA Antibody After HLA-incompatible Allogeneic Haematopoietic Stem Cell Transplantation

Haematological Malignancy Clinical Trial

Official title:

Kinectics of Donor-specific Anti-HLA Antibody After HLA-incompatible Allogeneic Haematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06395220
• Other study ID #: PekingUPH Chang Yingjun
• Status: Not yet recruiting
• Start date: May 1, 2024
• Est. completion date: January 1, 2026

Study information

• Verified date: April 2024
• Source: Peking University People's Hospital
• Contact: Prof. Ying-Jun Chang Chang
• Phone: 8610-88325949
• Email: rmcyj[@]bjmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Donor specific anti-HLA antibody (DSA) is closely related not only to primary graft rejection (GR) after HLA-incompatible transplantation, but also to the occurrence of primary PGF. Desensitisation therapy can reduce the level of DSA in patients and decrease the incidence of PGF after transplantation. However, most studies at home and abroad have focused on DSA levels in recipients before transplantation, risk factors and their effects on prognosis. Very few studies have focused on the rate of DSA positivity and its risk factors after transplantation. Therefore, this project aims to clarify the rate of DSA positivity after HLA-incompatible Allo-HSCT and reveal the influencing factors of post-transplantation DSA positivity with the help of a prospective, registry-based clinical cohort of HLA-incompatible transplant recipients, in order to provide a basis for the prevention and treatment of DSA-induced graft rejection or PGF.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 800
• Est. completion date: January 1, 2026
• Est. primary completion date: May 1, 2025
• Gender: All
• Age group: 15 Years to 60 Years

Eligibility

Inclusion Criteria:

Clinical diagnosis haematological disorders undergoing HLA-incompatible allogeneic haematopoietic stem cell transplantation Between 15 and 60 years-old Must sign the informed consent

Exclusion Criteria:

Withdraw of the signed informed consent for any reason Lack of ability to provide consent due to psychiatric or physical illness

Related Conditions & MeSH terms

• Haematological Malignancy
• Hematologic Neoplasms

Intervention

Other:
• Detection of donor-specific anti-HLA antibody (DSA)
Detection methods . Morphology: using microscope to observe the morphology of bone marrow. . Immunophenotyping: using multi-color flow cytometry (MFC) to detect immunophenotype of leukemia cells and leukemia-associated immunophenotype of bone marrow samples. . Cytogenetics analysis: G-band and/or fluorescence in situ hybridization (FISH) analysis are used in this study . Molecular detection: Real-time quantitative RT-PCR (RQ-PCR) and/or next generation sequencing techniques are used to detect the molecular marker, such as: PML/RARA, AML-ETO, BCR/ABL, and WT1. . HLA-Typing: HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined according to the literatures published by our group [Huo MR, et al. Bone Marrow Transplant. 2018;53(5):600-608].. . Other analyses: Detection of minimal residual diseases were performed using MFC and RQ-PCR according to the methods reported by our group [Li SQ, et al. Blood,2022;140(5):516-520].

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive rates of post-transplantation donor-specific anti-HLA antibody (DSA).	HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined according to the literatures published by our group [Huo MR, et al. Bone Marrow Transplant. 2018;53(5):600-608].	through study completion, an average of 2 years
Secondary	Acute graft-versus-host disease (aGVHD)	Acute GVHD was defined and graded from I to IV based on the pattern and severity of organ involvement [Sullivan KM. Graft-versus-host-disease. In: Thomas ED, Blume KG, Forman SJ (eds). Hematopoietic Cell Transplantation. 5nd edn. Blackwell Science: Boston, MA, USA, 2020, pp 515-536.].	2 years
Secondary	Chronic graft-versus-host disease (cGVHD)	Chronic GVHD was defined and graded according to the National Institute of Health criteria:[Biol Blood Marrow Transplant,2005,11: 945] that is, mild cGVHD reflects the involvement of no more than 1 or 2 organs/sites (except for lung) with a maximum score of 1; moderate cGVHD involves at least 1 organ/site with a score of 2 or =3 organs/sites with a score of 1 (or lung score 1); and severe cGVHD is diagnosed when a score of 3 is given to any organ (or lung score 2). The diagnosis is mainly based on clinical manifestations.	2 years
Secondary	Neutrophil engraftment	Neutrophil engraftment was defined as the first day of an absolute neutrophil count above 0.5×109/L for three consecutive days after the neutrophil nadir.	2 years
Secondary	Platelet engraftment	Platelet engraftment was defined as the first of 7 consecutive days during which the platelet count was at least 20×109/L without needing transfusion.	2 years
Secondary	Primary graft failure	Primary graft failure was defined as never achieved an ANC >0.5×109/L for thress consecutive days or an ANC >0.5×109/L without donor engraftment (autologous recovery).	2 years
Secondary	Secondary graft-failurefunction	Secondary graft-failure was defined as decline or loss of donor engraftment.	2 years
Secondary	Cumulative incidence of relapse	Relapse was defined by the morphological evidence of disease in the peripheral blood, BM or extramedullary sites. Time to relapse was defined from the date of transplantation to the date of disease recurrence. Patients exhibiting minimal residual disease (for example, the presence of BCR/ABL RNA transcripts by PCR) were not classified as having morphological relapse.	2 years
Secondary	Non-relaspe mortality (NRM)	Non-relapse mortality was defined as all causes of death other than those related directly to malignant disease itself, occurring at any time after transplantation.	2 years
Secondary	Disease-free survival (LFS)	Disease-free survival was defined as days from transplantation to disease progression after transplantation.	2 years
Secondary	Overall survival (OS)	Overall survival referred to patients who survived until the final follow-up time point.	2 years