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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
196
On the 7th day after allo-HSCT, the first dose of Luspatercept 1.0mg/kg was administered subcutaneously. If the peripheral blood HGB was \< 70g/L on the 21st day after allo-HSCT, the second dose of Luspatercept 1.0mg/kg was given subcutaneously; if the peripheral blood HGB was ≥ 70g/L on the 21st day after allo-HSCT, no second dose of Luspatercept subcutaneous injection was given.
The patient will receive the best supportive treatment including blood transfusion.
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China
Cumulative incidence of poor erythroid engraftment
Poor erythroid engraftment after allo-HSCT is defined as HGB \< 70g/L at 28 days post-transplantation and the inability to discontinue red blood cell transfusion in the case of complete donor engraftment.
Time frame: 28 days
Red blood cell units
The number of red blood cell units administered
Time frame: 28 days
Overall survival
Will calculate time from random assignment until death from any cause.
Time frame: 1 year
Disease-free survival
Will calculate time from random assignment until relapse or death from any cause
Time frame: 1 year
Cumulative rate of poor graft engraftment
The definition of PGF is as follows: More than 28 days after transplantation, there is at least a continuous period of 3 days of two-line or three-line blood cell reduction (absolute neutrophil count \< 0.5 × 109/L, platelet (PLT) \< 20 × 109/L, hemoglobin (HGB) \< 70 g/L), and blood transfusion support treatment is required; bone marrow examination indicates a low degree of bone marrow hyperplasia; complete donor engraftment; no active severe GVHD or hematological recurrence.
Time frame: 1 year
Relapse
Will calculate time from random assignment until relapse
Time frame: 1 year
Non-relapse mortality
Defined as death from any cause not subsequent to relapse
Time frame: 1 year
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