eligibility_summary
Eligible: SCD age 2–<25 with HLA-identical sibling donor with major ABO incompatibility or alloantibodies to donor RBC antigens, ANC ≥1×10^9/L, platelets ≥100×10^9/L, Karnofsky/Lansky ≥70. Requires ≥1 severe SCD event: stroke/TCD/MRA changes, ACS, pain crises, chronic transfusions, priapism, or splenic sequestration. Exclude: life expectancy <6 mo, pregnancy, HIV/HBV/HCV or uncontrolled infection, liver/cardiac/renal/pulmonary dysfunction or asthma, or an equivalent ABO-compatible sibling donor.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2, single-arm study in SCD patients with anti‑donor RBC antibodies/major ABO mismatch adds daratumumab before matched‑sibling nonmyeloablative HCT to prevent pure red cell aplasia. Interventions: daratumumab (IgG1k anti‑CD38 monoclonal antibody, depletes CD38+ plasma cells/plasmablasts/B cells via ADCC/CDC/apoptosis to remove alloantibodies), alemtuzumab (anti‑CD52 mAb, broad T‑ and B‑lymphocyte depletion for conditioning), low‑dose total‑body irradiation 300 cGy (immuno‑/myelosuppression to aid engraftment), and sirolimus (mTORC1 inhibitor, blocks IL‑2–driven T‑cell proliferation, favors Tregs, GVHD prophylaxis). Targets/pathways: CD38+ antibody‑secreting cells, CD52+ lymphocytes, mTOR signaling in T cells, and hematopoietic/immune cells sensitive to radiation, overall goal is to reduce alloantibodies, suppress host immunity, and enable durable donor RBC engraftment.