LUSPATERCEPT REDUCES THE BURDEN OF RED BLOOD CELL TRANSFUSION IN PATIENTS WITH BETA -THALASSEMIA AND COMORBIDITIES: THE EXPERIENCE OF A SINGLE THALASSEMIA AND SICKLE CELL UNIT IN A UNIVERSITY HOSPITAL

ABSTRACT

Background: An erythroid maturation agent, Luspatercept is approved to treat adults with β -thalassemia. Its availability in Greece coincided with severe blood shortages due to the COVID outbreak, making its administration even more necessary. Aims: Luspatarept's usage in patients with comorbidities. Methods: Between May and December 2021, luspatercept was administered for a period of 12 to 24 weeks to twelve individuals with confirmed β -thalassemia (β 0/β + 4/12, β +/β +3/12, β 0/β ++1/12, β 0/β 01/12,β +/β ++1/12) and significant comorbidities such as chronic heart failure (3/12), osteoporosis (3/12), atrial fibrillation (2/12), extramedullary hematopoiesis (2/12) and cirrhosis (1/12). The average age was 48.3 years;7male /5 female. Prior to initiating luspatercept, the patient's medical history was reviewed for risk factors for thrombophilia (9/12 had low protein S and C and 2/12 had also low ATIII) as well as anticoagulant (4/12 on acenocoumarol) and antiplatelet (3/12 on aspirin ) medication related to splenectomy (10/12) or past thrombotic episodes (4/12).Transfusion requirements, transfusion intervals, mean hemoglobin and LDH values were documented for 12 weeks prior to and during luspatercept initiation. To maintain stable blood volumes in each transfusion, prestorage leukoreduced RBCs with an average volume per unit of 320 ml was used. Results: Table 1 summarizes the study's main results.Statistical significance is p <0.05. Throughout treatment, all but one patient (11/12) received a dose of 1 mg/kg. One patient did not respond to a dose increase of 1.25 g / kg and discontinued on week 12. Additionally, two other luspatercept responders discontinued treatment after the 12th and 24th week, respectively, due to significant fatigue. After 12 and 24 weeks, all patients who continued in luspatercept had a significant decrease in transfusion blood needs, approximately -29.4% and -36.1 % compared to baseline. They also showed significant increase in transfusion intervals for an average of 20.7 days. In addition, it became apparent that, although the volume of blood supplied was reduced and the interval between transfusions increased, the patients' hemoglobin levels remained adequately high in luspatercept treated patients. LDH as hemolysis biomarker, did not reveal any significant changes. During the follow-up period, no patient reported progression of existing comorbidities or the development of new ones. As far as their cardiovascular disease is concerned, the patients clinical status was stable NYHA II despite the reduction of transfusions. Six months after taking luspatercept, one patient showed an improvement in extramedullary hematopoiesis as evaluated by magnetic resonance imaging. Additionally, despite the presence of predisposing factors and the significant increase of platelets, no new thrombosis developed. Summary/Conclusion: In patients with significant comorbidities, luspatercept significantly decreased transfusion burden and prolonged transfusion intervals , without any observed worsening of their comorbidities or development of new ones. (Table Presented).