Clinical Study on the Treatment of Poor Erythroid Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation with Luspatercept

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematological diseases. Donor derived hematopoiesis and immune reconstruction are the basis for the success of allo-HSCT. After allo-HSCT, some patients' hematopoiesis has been converted to donor source, but the recovery of hematopoiesis is delayed or incomplete, resulting in poor graft function (PGF) after transplantation. Poor erythroid engraftment refers to HGB ≤ 80g/L and inability to detach from red blood cell transfusion after 28 days of transplantation. It is closely related to donor recipient blood type incompatibility, acute and chronic graft versus host disease (GVHD), transplantation associated thrombotic microangiopathy (TA-TMA), autoimmune hemolytic anemia (AIHA), stem cell source, pre-treatment regimen strength, HLA mismatch, cytomegalovirus (CMV) infection, and other factors. The sustained decrease in hemoglobin after transplantation is a poor prognostic factor for allo HSCT, seriously affecting the long-term survival of patients. At present, there are limited and ineffective treatment methods for red blood cell implantation. Luspatercept is a recombinant fusion protein composed of a modified IIB type human activator receptor (ActRIIB) extracellular domain connected to the crystallizable fragment of human immunoglobulin G1 (IgG1 Fc) region. It can inhibit the activation of the Smad2/3 signaling pathway in erythroid precursor cells by binding to TGF-β ligands. It can also inhibit Smad2/3 activation in mesenchymal stromal cells, promoting normal hematopoietic stem/progenitor cell migration and homing, thereby restoring their hematopoietic function. Objective To observe of the efficacy and safety of Luspatercept in treating poor erythroid engraftment after allo-HSCT. Patients and Methods 16 patients with poor erythroid engraftment after allo-HSCT from June 2022 to December 2023 were inrolled in the study. Among them, there were 10 males and 6 females; 5 cases of HLA identical transplantation and 11 cases of HLA haploidentical transplantation; There were 7 cases of major ABO-incompatibility, 3 cases of both major and minor ABO-incompatibility, 2 cases of minor ABO-incompatibility, and 4 cases of ABO-compatibility; 16 patients were treated with a myeloablative conditional regimen. All patients were treated with Luspatercept (1.0mg/kg per-3 weeks) (combination therapy strategy for patients with clear etiology); After two consecutive administrations, there was no increase in hemoglobin levels, the dosage of Luspatercept was increased to 1.3mg/kg. Hemoglobin returned to the normal range, and Luspatercept was maintained once before discontinuing the medication. Result Among the 16 patients, 1 was diagnosed with pure red blood cell aplastic anemia, 1 with AIHA, 2 with CMV infection, and 2 with acute GVHD. The other patients had no definite cause. The above 6 patients with clear causes were treated with Luspatercept and glucocorticoids/ganciclovir. The other 10 patients were treated with Luspatercept alone. Among the 16 patients, 12 patients (75%) were effective (hemoglobin returned to above 80 g/L), with a median onset time of 6 weeks. Among them, 8 patients successfully discontinued the medication of Luspatercept, and hemoglobin was able to be maintained within the normal range. Conclusion Luspatercept can effectively treat poor erythroid engraftment after allo-HSCT, and its effectiveness and safety will be further validated through multi-center prospective and randomized controlled studies.