Comparison of safety and efficacy of liberal versus restrictive red blood cell transfusion thresholds on the quality of life in patients with myelodysplastic syndromes: a systematic review and meta-analysis

Background: Myelodysplastic syndromes (MDS) are primarily managed with red blood cell (RBC) transfusions, as stem cell transplantation is unsuitable for most patients. Anaemia, presenting with fatigue, pallor, and dyspnoea, markedly impairs quality of life (QoL), making selection of optimal haemoglobin (Hb) thresholds for transfusion a key clinical challenge. However, comparative evidence for liberal versus restrictive transfusion strategies remains limited. Methods: We performed a systematic review evaluating liberal versus restrictive RBC transfusion thresholds in adults with MDS not undergoing curative treatment such as stem cell transplantation. Primary outcome was health-related QoL measured by validated instruments. Secondary outcomes included mortality, transfusion reaction, iron overload, RBC utilisation and rise in ferritin level. Results: Of 4,295 records screened, 212 articles underwent full-text review, with three RCTs meeting inclusion criteria. Liberal transfusion strategies were associated with improved QoL compared to restrictive approaches, with pooled standardised mean difference (Hedges g) of 0.54 (95% CI 0.06–1.02; p = 0.33; I²=9.7%). Subgroup analysis of EQ‑5D outcomes across studies revealed minimal but statistically significant difference between strategies (pooled mean difference 0.084; 95% CI: 0.033 to 0.134). Mortality (hazard ratio 0.913; 95% CI 0.167–4.98) and transfusion reactions (risk difference − 0.01; 95% CI-0.10 to 0.09) did not differ. Notably, liberal thresholds required average of 4 additional RBC units per patient (95% CI 1.43–6.79), raising concerns about iron overload (rise in ferritin; mean difference 868 µg/L; 95% CI 482–1255). Conclusion: Limited evidence suggests that liberal transfusion strategies in MDS may improve short-term QoL but at the cost of increased transfusion burden, with no clear impact on survival or safety. A patient-centred, multidisciplinary approach remains essential when tailoring transfusion thresholds.