In a small retrospective study published in the Annals of Hematology, researchers reported that luspatercept demonstrated clinical activity in twelve patients with severe anemia resulting from poor erythroid engraftment after allogeneic hematopoietic stem cell transplantation. The central finding was that eleven of the twelve patients achieved an erythroid response to the treatment, which allowed them to discontinue red blood cell transfusions. This observation suggests that luspatercept may offer a therapeutic avenue for a specific and difficult-to-manage complication of stem cell transplantation, where bone marrow failure is limited to the red blood cell lineage while other cell lines recover successfully.
The clinical challenge addressed in this study arises when patients achieve myeloid and megakaryocytic engraftment but fail to recover adequate red blood cell production. In such cases, patients remain dependent on regular red blood cell transfusions, a condition that complicates long-term management. The management of this specific form of anemia remains difficult, prompting the investigation of luspatercept. The study focused on hemoglobin recovery, transfusion outcomes, and changes in bone marrow erythropoiesis to evaluate the drug’s potential utility in this niche population, where persistent poor erythroid recovery often leaves patients transfusion-dependent despite neutrophil and platelet engraftment.
The study team retrospectively reviewed medical records from twelve patients treated at their center between January 2023 and December 2025. All participants had undergone allogeneic hematopoietic stem cell transplantation and had achieved complete donor chimerism, confirmed by short tandem repeat analysis. Despite successful engraftment of other blood cell lines, their peripheral blood hemoglobin levels remained below 80 g/L up to two months after transplantation. The underlying diseases included acute myeloid leukemia in five patients, acute lymphoblastic leukemia in three, aplastic anemia in three, and myelodysplastic syndrome in one. The median age of the cohort was 35.5 years, with a range from 21 to 61 years, and the group consisted of five males and seven females.
Luspatercept was administered in addition to conventional therapy for these patients. The researchers defined an erythroid response as an increase in hemoglobin exceeding 15 g/L from baseline. This response was confirmed by a subsequent 14-day period during which no red blood cell transfusion was administered. Time to response was calculated as the interval from the first luspatercept administration to the first observation of this hemoglobin increase. Because hemoglobin was generally measured weekly, the post-treatment values referred to the measurement recorded at the first documented erythroid response.
The primary results indicated that eleven of the twelve patients, representing 91.7 percent of the cohort, achieved an erythroid response. Only one patient did not respond to the treatment. Among the responders, the median time to response was 18 days, with a range extending from 7 to 75 days. The median hemoglobin level increased from 44 g/L before treatment to 113.5 g/L after treatment, corresponding to a median increase of 65 g/L. The range of hemoglobin levels before treatment was 31 to 70 g/L, while the post-treatment range was 43 to 142 g/L. Notably, none of the eleven responders required further red blood cell transfusions after the initiation of luspatercept treatment.
Bone marrow assessments provided additional insights into the response. Before treatment, bone marrow erythroid proliferation was active in five patients, or 41.7 percent, and decreased in seven patients, or 58.3 percent. After treatment, the corresponding numbers shifted, with active proliferation observed in eleven patients, or 91.7 percent, and decreased proliferation in only one patient, or 8.3 percent.
Exploratory analyses revealed potential correlations between baseline bone marrow characteristics and the kinetics of response. Responders with active baseline erythroid proliferation had a shorter time to response compared to those with decreased erythroid proliferation, a difference that was statistically significant with a P-value of 0.034. Furthermore, the baseline erythroid proportion was negatively correlated with the time to response, with a Spearman rho of -0.65 and a P-value of 0.032. Additionally, the baseline erythroid proportion showed a positive trend with the magnitude of hemoglobin increase, with a rho of 0.55 and a P-value of 0.066, although this association did not reach conventional statistical significance.
The safety profile of luspatercept in this cohort was characterized by generally mild adverse events. Observed side effects included abdominal distension, diarrhea, rash, and edema. All of these adverse events were graded as grade 1, except for edema, which ranged from grade 1 to grade 2. The median follow-up after the last luspatercept administration across the entire cohort was 604 days, with a range of 18 to 983 days. Among the responders specifically, the median duration of follow-up was 706 days, ranging from 207 to 983 days, providing a substantial period of observation for the durability of the response.
The study has several limitations that must be considered when interpreting the results. The sample size was small, comprising only twelve patients, which limits the statistical power and generalizability of the findings. The retrospective design of the study may introduce selection bias and does not allow for causal inference regarding the efficacy of luspatercept. The authors noted that while baseline marrow erythroid findings may be associated with response kinetics, this exploratory observation requires validation in larger studies. Despite these limitations, the study provides preliminary evidence that luspatercept is clinically active and tolerable in patients with anemia related to poor erythroid engraftment after allogeneic hematopoietic stem cell transplantation.
Subject of Research: Clinical activity of luspatercept in treating anemia after allogeneic hematopoietic stem cell transplantation
Article Title: Clinical activity of luspatercept in patients with poor erythroid engraftment after allogeneic hematopoietic stem cell transplantation
Article References: Zhang, L., Li, S., Wang, F., Zhan, Y., Cheng, W., Zhao, M., Zhao, P., Xu, W., Huang, Y., Yang, X., Zhang, T., Li, Y., Liu, Y., & Zhu, H. (2026). Clinical activity of luspatercept in patients with poor erythroid engraftment after allogeneic hematopoietic stem cell transplantation. Annals of Hematology. https://doi.org/10.1007/s00277-026-07341-1
Image Credits: AI Generated
DOI: 10.1007/s00277-026-07341-1
Keywords: luspatercept, anemia, hematopoietic stem cell transplantation, erythroid engraftment, red blood cell transfusion, retrospective study, bone marrow, hemoglobin recovery, Clinical, activity, patients, poor
