Allogenic Megakaryocyte Therapy in patients with Refractory Thrombocytopenia

BACKGROUND Patients with refractory thrombocytopenia (RT) are not sensitive to conventional therapies, such as platelet transfusions and thrombopoietin receptor agonists (TPO-RAs). The persistently high risk of life-threatening hemorrhage in this population highlights the urgent need for novel therapeutic strategies. Megakaryocyte (MK)-based therapies have emerged as a promising alternative, as MKs are the natural precursor cells responsible for platelet production. However, whether allogeneic MK therapy can improve platelet counts and function in patients with RT remains unclear. METHODS We evaluated HLA-mismatched allogeneic MK therapy in 10 patients with RT following allogeneic hematopoietic stem-cell transplantation (allo-HSCT). All patients exhibited no response after at least one month of continuous treatment with TPO-RAs or other thrombopoiesis promoting therapies. MKs were expanded ex vivo and administered in a single infusion at one of three doses (1x10^6, 5x10^6, or 1x10^7 MKs per kilogram of body weight). Safety and efficacy were closely monitored. RESULTS MK infusion had minimal impact on inflammatory cytokine levels and coagulation parameters of patients. Among the 10 patients treated, 8 (80%) demonstrated a clinical response; including 3 complete response, and 5 partial response. Clinical improvement was observed within 28 days after infusion across all dose levels. CONCLUSIONS Among 10 patients with RT, 8 responded to MK therapy without experiencing major toxic effects. (ClinicalTrials.gov number, NCT06534255 )