Introduction: Anemia is common in hematologic malignancies, and RBC transfusion is a cornerstone of supportive care. However, the optimal hemoglobin transfusion threshold remains poorly defined. Evidence comparing restrictive and liberal strategies specifically in hematologic malignancies is limited. This systematic review and meta-analysis evaluate the safety and efficacy of restrictive versus liberal RBC transfusion thresholds in this population.

Aim: To evaluate the efficacy and safety of restrictive versus liberal RBC transfusion thresholds in patients with hematological malignancies using systematic review and meta-analytic methods.

Method: ▪ Systematic review and meta-analysis following PRISMA 2020 guidelines. ▪ MEDLINE/PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus searched from inception through April 2026. ▪ Included RCTs, prospective/retrospective cohort studies, and cross-sectional studies comparing restrictive vs. liberal RBC transfusion thresholds. ▪ Included adult and pediatric patients with hematologic malignancies. ▪ Two independent reviewers conducted screening, data extraction, and risk-of-bias assessment. ▪ Risk of bias assessed using Cochrane RoB 2 for RCTs and ROBINS-I for observational studies. ▪ Pooled estimates calculated using random-effects DerSimonian–Laird models. ▪ Heterogeneity assessed using I² and Cochran’s Q. ▪ Certainty of evidence assessed using GRADE.

Result: • 12 studies met eligibility criteria, including 3 RCTs, 8 retrospective cohorts, and 1 cross-sectional study, enrolling 4,345 patients across 9 countries. • Hematologic diagnoses included leukemia, lymphoma, myeloma, MDS, and mixed malignancies. Liberal Hb thresholds ranged from 6–10 g/dL, while restrictive thresholds ranged from 7–9.5 g/dL. • No study was rated at low risk of bias; observational studies were predominantly rated at high risk of bias. • All-cause mortality: No significant difference between restrictive and liberal strategies (HR 1.18, 95% CI 0.82–1.71; p = 0.38; I² = 72.8%). • The largest leukemia cohort (n = 2,511) reported higher mortality with the restrictive strategy (HR 1.73, 95% CI 1.30–2.30), while other studies showed no significant difference. • RBC transfusion exposure: Restrictive strategies resulted in 2.07 fewer RBC units on average (95% CI, 0.88–3.25; p = 0.001; I² = 82.6%). • Infection/febrile neutropenia: No significant difference between strategies (RR 1.00, 95% CI 0.76–1.31; p = 0.99; I² = 13.4%).• Hospital length of stay: No significant difference (MD +0.22 weeks, 95% CI −0.04 to +0.47; p = 0.10; I² = 60.2%), although the direction favored shorter hospitalization with restrictive transfusion. • Significant bleeding: Only one study provided comparative data (RR 0.51, 95% CI 0.02–11.50); evidence was insufficient for a definitive conclusion. • ICU admission: No significant difference was observed in the single available study (RR 1.04, 95% CI 0.63–1.73). • Other outcomes: Comparative data for thromboembolic events, readmission, and transfusion reactions were unavailable, while quality-of-life data were limited to one study. •Evidence certainty: No outcome reached moderate or high certainty; certainty ranged from low to very low because of risk of bias, heterogeneity, small sample sizes, and incomplete outcome reporting

Conclusion: Restrictive transfusion thresholds reduce RBC exposure without clear evidence of harm, but the certainty of evidence is low due to study limitations, heterogeneity, and incomplete reporting. Larger disease-specific randomized trials are needed to define the safest transfusion strategy in this population.