Luspatercept in Preventing Poor Erythroid Engraftment for Hematological Malignancies With Moderate to Severe Myelofibrosis

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for hematological malignancies. Poor erythroid engraftment after transplantation is a serious complication, especially in patients with moderate to severe myelofibrosis (MF). Currently, there is a lack of effective prevention strategies for poor erythroid engraftment after transplantation. Luspatercept, a novel TGF-β superfamily signaling pathway modulator, has shown potential in small-sample studies for the treatment and prevention of post-transplant anemia. Given the high proportion and poor prognosis of poor engraftment function in hematological malignancies with moderate to severe myelofibrosis after transplantation, we plan to conduct a prospective, multicenter, randomized controlled study to explore the efficacy and safety of luspatercept in preventing poor erythroid engraftment after allo-HSCT in hematological malignancies with moderate to severe myelofibrosis.

Exploring appropriate prevention strategies for poor erythroid engraftment during transplantation is not only a significant scientific issue but also a major clinical problem. Luspatercept is a recombinant fusion protein that can target and regulate the signaling pathway of the transforming growth factor-β (TGF-β) superfamily. By binding to multiple TGF-β superfamily ligands, it weakens the Smad2/3 signaling pathway, thereby promoting the maturation and generation of red blood cells. In recent years, some small-sample studies have explored the efficacy and safety of luspatercept for preventive treatment in patients with hematological malignancies who received allo-HSCT, showing certain efficacy. However, these studies were retrospective and requires large-sample, prospective, randomized controlled studies for further verification. Currently, there are no prospective studies on preventive treatment for poor erythroid engraftment after allo-HSCT in patients with hematological malignancies. The presence of fibrosis in the bone marrow before transplantation (MF), especially moderate/severe MF, is one of the main causes of post-transplant PGF. A small-sample clinical trial in our center previously showed that in patients with MDS/MPN and acute leukemia with MF grade 2/3, applying luspatercept at +7 and +21 days after transplantation could reduce the risk of early red cell transfusion after transplantation, and showed good safety. Based on the current research status and our previous studies, we plan to conduct a prospective, multicenter, randomized controlled study to explore the efficacy and safety of luspatercept in preventing poor erythroid engraftment after allo-HSCT in patients with hematological malignancies accompanied by moderate/severe MF.

Inclusion Criteria: * Age 18-65 years old, gender not restricted; * ECOG score 0-2 points; * Hematological malignancies with moderate to severe myelofibrosis * Willing to undergo the first allo-HSCT with a suitable donor * In a CR state before transplantation. Exclusion Criteria: * Has previously undergone allo-HSCT; * ECOG score is 3-5; * Expected lifespan after transplantation is less than 30 days; * Has severe cardiac dysfunction, severe arrhythmia or severe pulmonary dysfunction (obstructive and/or restrictive ventilation disorder); * Has severe liver dysfunction, with liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL)) more than twice the upper limit of normal; * Has severe renal dysfunction, with creatinine (Cr) more than twice the upper limit of normal or 24-hour creatinine clearance rate (Ccr) lower than 30 ml/min; * Has severe active bleeding; * Patients judged by the investigator to be unsuitable for participating in this trial.