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A combination chemotherapy regimen used primarily as a reduced-intensity conditioning (RIC) protocol before hematopoietic cell transplantation (HCT), particularly for patients with non-malignant diseases including primary immune deficiencies and inherited errors of immunity. The regimen consists of four components: 1. **Alemtuzumab**: A monoclonal antibody that targets CD52, depleting T cells and other lymphocytes to prevent graft rejection and reduce graft-versus-host disease (GVHD). 2. **Fludarabine**: A purine nucleoside analog that inhibits DNA synthesis and repair, affecting primarily lymphocytes. 3. **Melphalan**: An alkylating agent that cross-links DNA, preventing cell division. 4. **Thiotepa**: An alkylating agent that cross-links DNA strands, preventing cell replication. This combination provides immunoablation and myeloablation while being less toxic than traditional myeloablative conditioning regimens. It's particularly valuable for pediatric patients and those with non-malignant diseases who may not tolerate more intensive conditioning. The regimen has shown favorable outcomes with high rates of engraftment, low rates of severe GVHD, and good overall survival in various studies. It's been successfully used with different donor sources, including unrelated cord blood transplants. Typical administration involves: - Alemtuzumab: Given on days -22 to -19 (test dose followed by full doses) - Hydroxyurea: Sometimes added from days -22 to -10 - Fludarabine: Given on days -9 to -5 - Melphalan: Administered on days -4 and -3 - Thiotepa: Given on day -2 This regimen is particularly notable for being radiation-free while still providing effective conditioning for successful transplantation.
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