Haematological Malignancy
Conditions
Brief 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.
Interventions
OTHERDetection of donor-specific anti-HLA antibody (DSA)
Detection methods 1. . Morphology: using microscope to observe the morphology of bone marrow. 2. . Immunophenotyping: using multi-color flow cytometry (MFC) to detect immunophenotype of leukemia cells and leukemia-associated immunophenotype of bone marrow samples. 3. . Cytogenetics analysis: G-band and/or fluorescence in situ hybridization (FISH) analysis are used in this study 4. . 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. 5. . HLA-Typing: HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined according to the literatures published by our group \[Huo MR, et al. Bone Marrow Transplant. 2018;53(5):600-608\].. 6. . Other analyses: Detection of minimal residual diseases were performed using MFC and RQ-PCR according to the methods reported by our group \[Li SQ, et al. Blood,2022;140(5):516-520\].
Sponsors
The First Affiliated Hospital of Zhengzhou University
Peking University First Hospital
The First Hospital of Jilin University
First Affiliated Hospital of Harbin Medical University
Peking University People's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to 60 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive rates of post-transplantation donor-specific anti-HLA antibody (DSA). | through study completion, an average of 2 years | HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined according to the literatures published by our group \[Huo MR, et al. Bone Marrow Transplant. 2018;53(5):600-608\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chronic graft-versus-host disease (cGVHD) | 2 years | 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. |
| Neutrophil engraftment | 2 years | 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. |
| Platelet engraftment | 2 years | 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. |
| Primary graft failure | 2 years | 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). |
| Acute graft-versus-host disease (aGVHD) | 2 years | Acute GVHD was defined and graded from I to IV based on the pattern and severity of organ involvement \[Sullivan KM. Graft-versus-host-disease. In: Thomas ED, Blume KG, Forman SJ (eds). Hematopoietic Cell Transplantation. 5nd edn. Blackwell Science: Boston, MA, USA, 2020, pp 515-536.\]. |
| Cumulative incidence of relapse | 2 years | 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. |
| Non-relaspe mortality (NRM) | 2 years | 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. |
| Disease-free survival (LFS) | 2 years | Disease-free survival was defined as days from transplantation to disease progression after transplantation. |
| Overall survival (OS) | 2 years | Overall survival referred to patients who survived until the final follow-up time point. |
| Secondary graft-failurefunction | 2 years | Secondary graft-failure was defined as decline or loss of donor engraftment. |
Countries
China
Outcome results
None listed