Luspatercept in patients with hematological diseases who have delayed erythroid recovery after allogeneic hematopoietic stem cell transplantation.

Abstract Introduction Delayed erythroid recovery after hematopoietic stem cell transplantation (HSCT) is a common and concerning complication. The current treatment is erythropoietin, but it is effective only in some patients; other therapies, such as corticosteroids and rituximab, carry significant infection risks, highlighting the unmet need for safer and more effective treatments. Luspatercept, a novel erythroid maturation agent, promotes late-stage erythroblast differentiation by modulating transforming growth factor β superfamily signaling pathway. Luspatercept is approved by FDA to treat patients with low-moderate-risk myelodysplastic neoplasms or β-thalassemia. However, its potential to enhance erythroid reconstitution after HSCT remains unexplored. Methods Seventeen patients with delayed erythroid recovery after allogeneic HSCT at our institution between August 2023 and April 2025 were included in this retrospective study and all of them achieved myeloid and megakaryocytic engraftment and STR complete mixed chimerism. The peripheral hemoglobin concentrations of these patients were detected less than 80 g/L after myeloid and megakaryocytic engraftment, and then the luspatercept administration was started with 1 mg/kg subcutaneously and continued every 21 days if no erythroid response was observed (defined as an elevated hemoglobin concentration of more than 15 g/L from baseline for at least 14 consecutive days without erythrocytes transfusions since the first dose). Results The median age of the patients was 53 (range 25 – 63) years and 10 (58.8%) patients were male. Among these patients, the underlying hematological diseases were acute myeloid leukemia (n = 6), acute lymphoblastic leukemia (n = 5), myelodysplastic neoplasms (n = 4), and aplastic anemia (n = 2), respectively; 10 (58.8%) patients achieved disease complete response before HSCT. Fourteen (82.4%) patients underwent haploidentical HSCT while the other 3 (17.6%) patients underwent HLA-matched HSCT. The ABO blood types of 8 (47.1%) patients were matched between the donors and recipients. All patients obtained neutrophil and platelet engraftment at a median of 12 (range 10 – 19) and 14 (range 11 – 26) days after HSCT, respectively. The luspatercept administration was initiated on a median of 112 (range 17 – 476) days after HSCT and the median number of times treated with luspatercept was 1 (range 1 – 4). Luspatercept showed good safety since no patient was observed obvious toxicities such as nausea, diarrhea, asthenia, or dizziness. The median peripheral hemoglobin concentration of all patients was 48 (range 36 – 60) g/L before luspatercept treatment. Eleven (64.7%) patients achieved erythroid response, among whom 8 (72.7%) remained erythroid response more than 8 weeks. Among those patients with erythroid response after luspatercept treatment, the median peripheral hemoglobin concentration increased from 49 (range 38 – 60) g/L to 78 (range 66 – 98) g/L (P < 0.001); notably, the median white blood cell and platelet counts increased as well [3.26 (range 1.61 – 8.40) ×10^9/L vs. 5.33 (range 2.45 – 9.31) ×10^9/L, P = 0.024; 34 (range 11 – 141) ×10^9/L vs. 70 (range 16 – 200) ×10^9/L, P = 0.009; respectively]. The median orthochromatic erythroblast ratio in bone marrow elevated from 16 (range 0 – 32) to 28 (range 12 – 37) (P = 0.025), whereas there was no difference in polychromatic erythroblast ratio. Besides, the median days from luspatercept treatment to erythroid response was 20 (range 3 – 61). When comparing the characteristic of patients with and without erythroid response, it is found that there was no difference in their peripheral blood cell counts or bone marrow erythroblast ratio at baseline. Conclusions Luspatercept is a promising agent for patients with hematological diseases who have delayed erythroid recovery after allogeneic HSCT. Further research is needed to explore its optimal clinical application and potential mechanisms in the context of allogeneic HSCT.