Anakinra for Prevention of Poor Graft Function in MDS Allo-HSCT

Preclinical evidence indicates that IL-1 inflammatory signaling suppresses bone marrow mesenchymal stromal cells (MSCs) from secreting stem cell factor (SCF), leading to failure of their hematopoietic supportive capacity, and that the interleukin-1 receptor antagonist (IL-1Ra, Anakinra) can reverse this process. Sustained low-level IL-1 signaling also drives hematopoietic stem cell (HSC) dysfunction, including progression of clonal hematopoiesis and transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). A prior phase 2 trial of IL-1 inhibition in lower-risk MDS demonstrated hematologic improvement without an increased risk of leukemic transformation. Based on these findings, this study hypothesizes that early administration of Anakinra after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS, by inhibiting IL-1β signaling, improving the bone marrow microenvironment, and reducing the occurrence of poor graft function (PGF), does not increase the risk of post-transplant relapse. The study comprises two parts: a dose-escalation phase to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of Anakinra in post-allo-HSCT patients, and an efficacy-validation phase to evaluate the preventive effect of Anakinra at the RP2D on PGF.

Inclusion Criteria: 1. Age 18-70 years (inclusive), male or female. 2. Confirmed diagnosis of MDS (2016 WHO classification) with an indication for hematopoietic stem cell transplantation. 3. Planned first allo-HSCT; donor type is an HLA-matched related donor, an HLA-matched unrelated donor, or a haploidentical donor. 4. Signed written informed consent before transplantation, with commitment to comply with study procedures and complete full follow-up. 5. ECOG performance status 0-2. 6. Adequate organ function to tolerate allo-HSCT: cardiac LVEF ≥50%; ALT/AST ≤3×ULN and total bilirubin ≤2×ULN; creatinine clearance ≥50 mL/min; DLCO ≥50% of predicted. 7. Women of childbearing potential must have a negative pregnancy test at screening and use effective contraception during the study and for 3 months after study end; male participants must use effective contraception during the study and for 3 months after study end. Exclusion Criteria: 1. Planned second transplant or prior allo-HSCT. 2. Active infection before transplantation (uncontrolled bacterial, fungal, or viral). 3. Hypersensitivity to Anakinra or E. coli-derived proteins. 4. Concurrent other malignancy (except cured non-melanoma skin cancer or carcinoma in situ of the cervix). 5. Pregnant or breastfeeding women. 6. HIV-positive, active hepatitis B (HBV-DNA \>10³ copies/mL), or active hepatitis C. 7. Clinical manifestations of HLH or MAS at screening. 8. Any other condition deemed unsuitable by the investigator and the DSMB (e.g., severe psychiatric illness, poor compliance).