A paraspinal extramedullary hematopoiesis with cauda equina syndrome in a transfusion-dependent thalassemia patient after treatment with luspatercept: A case report. Free

Introduction: Thalassemia is an inherited disorder characterized by mutations in the genes responsible for the production of the alpha and beta globin chains, which are essential components of hemoglobin. The clinical manifestations vary widely, ranging from asymptomatic cases to varying degrees of hemolytic anemia, extramedullary hematopoiesis (EMH), skeletal deformities, growth retardation, and iron overload—often secondary to regular blood transfusions. These manifestations depend largely on the specific thalassemia subtype.

The primary treatment for thalassemia includes regular blood transfusions and the administration of iron-chelating agents to manage iron overload and mitigate treatment-related complications. To enhance erythroid maturation, the erythroid-stimulating agent luspatercept (Reblozyl®) is employed in certain patients.

Case Presentation: We report the case of a 35-year-old woman with transfusion-dependent thalassemia major and a history of splenectomy, maintained on 3-week blood transfusion intervals. She was recently trialed on luspatercept, which was discontinued due to adverse effects. The patient initially presented with altered mental status, fever, and back pain. After clinical improvement with empirical treatment, she re-presented with bilateral lower limb weakness, saddle anesthesia, and difficulty ambulating, but no sphincter dysfunction. Neurologic examination revealed decreased lower limb strength and numbness in the perianal area. MRI of the spine demonstrated multiple paraspinal and presacral masses consistent with extramedullary hematopoiesis compressing the cauda equina. A high-intensity transfusion program was initiated (target hemoglobin >11 g/dL). Hydroxyurea was trialed but discontinued due to suspected pancytopenia. She later developed infections with MSSA and E. coli, requiring hospitalization and appropriate antimicrobial therapy. With physiotherapy and transfusion support, she regained significant mobility and functional improvement.

Discussion: This case illustrates the potential for EMH-associated cauda equina syndrome as a severe complication following luspatercept therapy in TDT patients. Although surgical and radiotherapeutic options are available, conservative management with hypertransfusion and physiotherapy may be efficacious, particularly in patients with mild to moderate neurologic impairment. Current literature lacks consensus regarding definitive treatment, underlining the need for individualized, multidisciplinary approaches.

Conclusion: While luspatercept offers considerable benefits in reducing transfusion burden in patients with TDT, clinicians should remain vigilant for rare but serious complications such as EMH. Our case highlights that non-invasive management strategies, including intensive transfusion regimens and physiotherapy, may restore function and avoid surgical intervention in select patients. Further reporting and data collection are necessary to inform evidence-based guidelines for the optimal management of EMH in this context.