eligibility_summary
Eligibility: SCD (including with a fully matched sibling donor), transfusion‑dependent α/β‑thalassemia, Diamond‑Blackfan anemia, or other non‑malignant hematologic disorders, Karnofsky/Lansky ≥60 (flexible per team), effective contraception if of/with childbearing potential. Exclusions: pregnancy/breastfeeding (negative test ≤7 days pre‑treatment), HIV+, uncontrolled infection, allergy to study drugs, psychosocial non‑adherence, or other investigator‑judged risks.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase II single-center allo-HSCT for high-risk hemoglobinopathies. Arms by donor: MSD (alemtuzumab+TBI, sirolimus+MMF), MSD/MUD (ATG+fludarabine+busulfan, tacrolimus+MMF), haplo/MMUD (ATG+thiotepa+cyclophosphamide+fludarabine+TBI, post-transplant cyclophosphamide, sirolimus+MMF). Mechanisms/types: Alemtuzumab (anti-CD52 monoclonal antibody) and Thymoglobulin/ATG (rabbit polyclonal anti-T-cell antibodies) deplete T cells to prevent rejection/GVHD. Fludarabine (purine analog antimetabolite) lymphodepletes. Busulfan and Thiotepa (alkylators) and TBI (radiation) myeloablate via DNA damage. Cyclophosphamide (alkylator) removes proliferating alloreactive T cells. Tacrolimus (calcineurin inhibitor) blocks IL-2 transcription, Sirolimus (mTOR inhibitor) blocks IL-2 signaling, Mycophenolate mofetil (IMPDH inhibitor) suppresses de novo purine synthesis in lymphocytes. Targets: T cells (CD52+, thymocyte antigens), IL-2/calcineurin/mTOR pathways, purine synthesis, DNA replication/repair, and marrow hematopoietic compartment, donor HSC infusion restores erythropoiesis.