Efficacy of Recombinant Human Erythropoietin in Enhancing Erythroid Hematopoietic Recovery after Allogeneic Hematopoietic Stem Cell Transplantation: A Meta-Analysis

Introduction

Chronic anemia is a common and significant complication following allogeneic hematopoietic stem cell transplantation (HSCT). Post-HSCT anemia often develops within 1 to 6 months after HSCT, patients may need packed red blood cell (pRBC) transfusions for up to one year, repeated transfusions can lead to iron overload and an increased risk of infections. This condition results from increased red cell utilization and decreased production, often linked to an inadequate erythropoietin (EPO) response. Erythropoiesis, regulated by EPO, is crucial for red blood cell (RBC) production, but after HSCT, EPO levels, while elevated, are insufficient for the degree of anemia, leading to chronic anemia. Recombinant human erythropoietin (RHuEPO) has shown potential in improving erythropoiesis and reducing pRBC transfusion requirements in patients undergoing HSCT. However, previous trials administering high doses of RHuEPO shortly after transplantation have yielded mixed results. This study evaluates the efficacy of RHuEPO in reducing transfusion needs and accelerating erythroid hematopoietic recovery post-HSCT.

Methods

A systematic search was conducted in PubMed, Cochrane Library, and Embase from inception to April 2024 to identify randomized controlled trials (RCTs) studying the effects of EPO in patients post-HSCT. Data were aggregated and analyzed using mean difference and a random effects model to compare the standard-of-care and recombinant human erythropoietin (RHuEPO) treatment cohorts. Key outcomes were time to 1% reticulocyte count, hemoglobin levels at specified time points, the number of packed red blood cell (pRBC) and platelet transfusions, and days to achieve pRBC transfusion independence. Heterogeneity was assessed and bias was evaluated using funnel plots.

Results

Of a total of 51 screened studies, 10 RCTs met the inclusion criteria, comprising 698 patients: 341 in the control group (no RHuEPO) and 357 in the intervention group (received RHuEPO). RHuEPO therapy was defined as a minimum dose of 30,000 IU/week. The RHuEPO intervention group reached the 1% reticulocyte count 6.5 days earlier than the control group (CI: -12.87, -0.21,P < 0.05). pRBC transfusion independence was achieved 5 days earlier in the RHuEPO intervention group compared to the control group (CI: -8.52, -01.45,P < 0.01). Although Hb levels measured one-month post-HSCT were slightly higher by 0.46 g/dL in the RHuEPO intervention group, this difference did not reach statistical significance. However, at two months post-HSCT, the RHuEPO intervention group's Hb level was 1.91 g/dL higher than the control group (CI: 0.05, 3.77,P < 0.05). Within the first 28 days post-HSCT, the RHuEPO intervention group required 2.66 fewer transfusions compared to the control group (CI: -4.81, -0.51,P < 0.05). In regard to RHuEPO side effects, our study showed that the RHuEPO intervention group had slightly lower rates of GVHD at 38% compared to 45% in the control group. Too few studies distinguished between the various grades of GVHD to evaluate. The rates of veno-occlusive disease in the RHuEPO intervention group were slightly lower than the control group with 8.7% and 9.9% respectively. The RHuEPO intervention group showed modestly increased rates of hypertension at 10.45% compared to 6.59% in the control group.

Conclusion

This first-of-its-kind meta-analysis demonstrates that recombinant human erythropoietin (RHuEPO) significantly improves erythroid hematopoietic recovery post-HSCT. The RHuEPO group achieved key milestones such as 1% reticulocyte count and pRBC transfusion independence significantly earlier than the control group. Notably, while RHuEPO can have side effects, our study found that the RHuEPO group experienced slightly lower rates of GVHD and veno-occlusive disease, with only a modest increase in hypertension incidence. These findings suggest that RHuEPO is a valuable adjuvant to standard post-HSCT care, potentially enhancing patient outcomes. Further research is warranted to optimize dosing and administration protocols.

No relevant conflicts of interest to declare.