Early Use of Luspatercept After Allogeneic HSCT Improves Erythroid Recovery and Transfusion Burden

Persistent anemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is common and clinically burdensome. Luspatercept, which promotes late-stage erythroid maturation, may accelerate red-cell recovery without broad immunosuppression. We conducted a single-center, retrospective cohort study with contemporaneous controls. Adults with post-transplant anemia (hemoglobin < 65 g/L despite ≥ 2 weeks of standard care), complete donor chimerism (≥ 95%), and disease remission were included. The primary endpoint was early erythroid response (≥ 15 g/L hemoglobin increase maintained ≥ 14 days without RBC transfusion during the first cycle). Secondary endpoints included time to hemoglobin ≥ 80 g/L, transfusion outcomes, marrow/peripheral erythroid kinetics, and safety. Of 96 patients, 49 received luspatercept (median start day + 21; 95.9% single dose) and 47 served as controls. An erythroid response occurred in 45/49 (91.8%) treated patients (median time, 11 days). Hemoglobin rose from 55 to 65 g/L at one week; platelets increased from 44 to 71×10^9/L while neutrophils remained stable. Using day + 21 as a common baseline, hemoglobin increments favored luspatercept at weeks 1 and 2; by day + 56, 89.8% versus 78.7% (luspatercept vs control) achieved hemoglobin ≥ 80 g/L. Within three weeks post-dose, fewer luspatercept recipients required RBC transfusion (10.2% vs 27.7%; p = 0.037). Paired marrows (n = 14) showed increased orthochromatic erythroblasts with reticulocytosis; paired sera (n = 29) showed decreases in IL-6, IL-5, and sIL-2R. Adverse events were grade 1 only; no grade ≥ 3 toxicities occurred, and CMV/EBV reactivation and acute GVHD rates were similar. Prospective randomized trials are warranted to confirm efficacy, refine timing/dosing, and assess transfusion burden, iron indices, durability, and patient-centered outcomes.