Impact of Thrombopoietin Receptor Agonists on Platelet Transfusion Requirements in Myelodysplastic Syndromes: An...

Thrombocytopenia in myelodysplastic syndromes (MDS) is associated with bleeding complications, transfusion dependence, and reduced quality of life. While platelet transfusions remain standard care, they carry limitations including short durability, alloimmunization, and infection risk. Thrombopoietin receptor agonists (TPO-RAs), such as eltrombopagand romiplostim, have emerged as potential alternatives, but their efficacy and safety remain incompletely defined.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TPO-RAs versus placebo in patients with MDS. Searches were performed across PubMed, EMBASE, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov from inception to January 4, 2025, following PRISMA 2009 guidelines. Eligible trials included adult patients with MDS receiving TPO-RAs with standardized background therapy. Outcomes included platelet transfusion incidence (primary), overall response, AML transformation, severe bleeding, mortality, hematologic improvement, and overall survival. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity was assessed using the I² statistic.

Ten RCTs involving 908 patients were included. TPO-RA treatment significantly reduced platelet transfusion incidence (RR 0.67, 95% CI, 0.54-0.86; I² = 10%). Subgroup analysis showed similar reductions with eltrombopag (RR: 0.74; 95% CI, 0.45-1.21) and romiplostim (RR: 0.66; 95% CI, 0.46-0.95). No statistically significant differences were found in overall response (RR 1.09, 95% CI, 0.73-1.64), AML transformation (RR 1.16, 95% CI, 0.88-1.52), grade ≥ 3 bleeding (RR 0.73, 95% CI, 0.47-1.12), hematologic improvement (RR 1.05, 95% CI, 0.84-1.33), overall survival (RR 0.88, 95% CI, 0.63-1.23) or mortality (RR 1.03, 95% CI, 0.90-1.18).

TPO-RAs significantly reduce platelet transfusion requirements in patients with MDS without increasing risks of AML progression or mortality. These agents provide effective supportive care for thrombocytopenic patients but do not confer survival or disease-modifying benefits. Future studies should investigate long-term outcomes, quality of life, and combination strategies with other disease-modifying therapies.