Cyclosporine in hematological disorders: mechanisms, clinical practice and emerging advances

Cyclosporine A (CsA) functions as a calcineurin inhibitor that perturbs T cell activation via calcineurin-nuclear factor of activated T cells (CaN-NFAT) signaling inhibitors, establishing its central role in hematological therapeutics. This review delineates the contemporary applications and mechanistic underpinnings of CsA across acquired bone marrow failure syndromes spanning severe and non-severe aplastic anemia (AA), myelodysplastic neoplasms, graft versus host disease (GVHD), and autoimmune cytopenias. We underscore individualized treatment algorithms steered by molecular biomarkers such as STAT3 mutational status, T cell receptor clonality, and telomere attrition, alongside the imperative of therapeutic drug monitoring at trough (C0) and 2-hour post-dose (C2) intervals to refine risk to benefit profiles. The manuscript further elaborates on pharmacological synergies between CsA and novel targeted agents including eltrombopag, ruxolitinib, and immune checkpoint inhibitors, while evaluating its capacity to surmount chemotherapeutic resistance and function as a bridging modality to CAR-T cell infusion. Lastly, we propose tiered management protocols for dose-limiting toxicities (nephrotoxicity and hypertension) and highlight emerging research frontiers in nanoformulation and artificial intelligence-guided therapeutic drug monitoring.