Aplastic Anemia, Leukemia, Lymphoma, Myelodysplastic Syndromes, Thalassemia
Conditions
Brief summary
This study tests whether a combination of three treatments - dexamethasone (a steroid), intravenous immunoglobulin (IVIG, a protein that helps the immune system), and an extra dose of donor mononuclear cells - can safely lower harmful antibodies called donor-specific antibodies (DSA) in patients who need a stem cell transplant from a half-matched (haploidentical) family donor. In these transplants, DSA are antibodies made by the patient's own body that attack the donor's stem cells. If DSA levels are high, the transplant is more likely to fail - the donor cells may not "take" (engraft). Currently, there is no single, simple, and reliable way to reduce DSA, and many existing methods have drawbacks. Based on the investigators' earlier experience in 11 patients, this three-part approach seemed to work well. All patients successfully engrafted, and DSA levels dropped quickly. Now the study team want to confirm these results in a larger, prospective, multicenter study. The investigators plan to enroll 60 patients aged 18-65 with blood cancers or other blood disorders who need a haploidentical transplant, have DSA levels above 500 MFI (a measure of antibody strength), and have no other suitable donor available. Participants will receive: * Dexamethasone (25 mg/m²) for 4 days before transplant, * IVIG (1 g/kg) one day before transplant, * Extra mononuclear cells on transplant day - the extra amount depends on how high their DSA level is (low, medium, or high). The main goal is to see how many patients have primary graft failure (when the donor cells never engraft). The study team will also measure how long it takes for blood counts to recover, rates of graft-versus-host disease, survival, and side effects. All participants will be followed for 1 year. This study will help the investigators find out whether this combination is a safe, simple, and effective way to improve transplant success for patients with DSA who have no other donor options.
Interventions
BIOLOGICALIntravenous Immunoglobulin
1 g/kg intravenously on day -1 prior to transplant.
DRUGDexamethasone
25 mg/m² intravenously for 4 days prior to transplant (days -4 to -1).
BIOLOGICALMononuclear Cells
Additional donor MNCs infused on day 0. Dose stratified by baseline DSA MFI level: ≤5000: +2±2×10⁸/kg; 5000-10000: +4±2×10⁸/kg; \>10000: +6±2×10⁸/kg.
Sponsors
Hematology department of the 920th hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of benign or malignant hematological diseases (including leukemia, lymphoma, thalassemia, aplastic anemia, myelodysplastic syndromes, etc.) confirmed by NCCN guidelines, and determined by the investigator to require allogeneic hematopoietic stem cell transplantation. 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3. 3. Donor-specific antibody (DSA) mean fluorescence intensity (MFI) \> 500. 4. Age between 18 and 65 years (age limits are also captured separately in the eligibility module). 5. Body weight between 40 kg and 100 kg. 6. No other suitable donor available (i.e., no DSA-negative related donor or unrelated donor).
Exclusion criteria
1. Patients unsuitable for transplantation or without willingness to undergo transplantation, or diagnosed with non-hematological diseases. 2. Estimated life expectancy \< 1 month. 3. Known allergy to any drug or intervention used in the study regimen. 4. Pregnancy, lactation, active severe infection, or severe major organ dysfunction. 5. Severe psychiatric or neurological disorders that may affect the ability to provide informed consent and/or to report adverse events or comply with observation. 6. Refusal or inability to sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Graft Failure (PGF) | Day +28 post-transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil and Platelet Engraftment Time | Up to 28 days post-transplant | — |
| Dynamic Changes in Donor-Specific Antibody (DSA) MFI Levels | Pre-transplant (day -14 to -1) through day +22 post-transplant | — |
| Incidence of Acute and Chronic Graft-Versus-Host Disease | Up to 1 year post-transplant | Cumulative incidence of acute GVHD (aGVHD) graded by standard criteria within 100 days post-transplant, and chronic GVHD (cGVHD) graded by NIH consensus criteria from day +100 through 1 year post-transplant. |
| Overall Survival and Disease-Free Survival | Up to 1 year post-transplant | Overall survival (OS) defined as time from transplant to death from any cause. Disease-free survival (DFS) defined as time from transplant to relapse, progression, or death from any cause. Estimated using Kaplan-Meier method at 1 year. |
| Incidence of Adverse Events | Up to 1 year post-transplant | Incidence of infectious complications (bacterial, viral, fungal), bleeding events, and other treatment-emergent adverse events. Graded according to CTCAE criteria. |
Contacts
CONTACTSanbin Wang
CONTACTXi Xiong
Outcome results
None listed