alemtuzumab + cyclophosphamide + pentostatin + sirolimus

This is a combination regimen consisting of four agents—alemtuzumab, cyclophosphamide, pentostatin, and sirolimus—used primarily as part of reduced-intensity conditioning (RIC) protocols for allogeneic hematopoietic cell transplantation (HCT). - Alemtuzumab is a humanized monoclonal antibody targeting CD52 on lymphocytes, leading to profound lymphodepletion via antibody-dependent cellular cytolysis and complement-mediated lysis. - Cyclophosphamide is an alkylating agent that crosslinks DNA, resulting in immunosuppression and cytotoxicity against rapidly dividing cells. - Pentostatin is a purine analog that inhibits adenosine deaminase, causing accumulation of toxic metabolites in lymphocytes and further immunosuppression. - Sirolimus (rapamycin) inhibits the mammalian target of rapamycin (mTOR), blocking T-cell activation and proliferation by inhibiting IL-2 signal transduction. This combination aims to achieve sufficient immunosuppression to facilitate donor stem cell engraftment while minimizing toxicity compared to myeloablative regimens. It has been studied particularly in patients with hematologic malignancies or nonmalignant disorders undergoing HCT[1][4]. The regimen may also be used for graft-versus-host disease prophylaxis.