Further research on the treatment of extramedullary hematopoiesis in transfusion-dependent beta-thalassemia is needed.
Currently, there are no clear guidelines for the management of extramedullary hematopoiesis in transfusion-dependent beta-thalassemia.
Extramedullary hematopoiesis (EMH) is a rare complication of beta-thalassemia (BT) that is more commonly seen in mild to moderate cases of BT. But a review published in Annals of Medicine suggests that EMH is also an important clinical complication in transfusion-dependent BT (TDT) and warrants prospective studies of optimal treatment strategies.
BT, a condition characterized by reduced production of the beta-globin chain of hemoglobin, is estimated to affect up to 5% of the world’s population. According to clinical features, BT can be stratified into 2 main types: thalassemia major (TM) and thalassemia intermedia (TI). Patients with TM are usually dependent on regular blood transfusions, while those with TI are not dependent on transfusions (NTDT). EMH, a rare complication of BT and other blood disorders, occurs when blood cells grow in places outside the bone marrow in response to reduced production in the bone marrow. EMH is reported in up to 20% of patients with NTDT versus less than 1% of patients with TDT.
“Treatment options for thalassemia patients with EMH depend on the location and symptoms of mass effect, including hypertransfusion, surgical excision, radiation therapy, hydroxyurea, or various combinations of therapies” , wrote the authors. “The main objective of this review is to pool all available data on the presentations and management of EMH in the setting of TDT, providing synthetic statistics.”
A literature search yielded 253 reported cases of EMH in patients with TM, encompassing 2 retrospective studies and 70 case reports. The mean age at presentation of EMH was 35 years and the spinal cord was the most frequently involved site of EMH (87.7% of cases).
Most cases (72%), including those from retrospective studies, did not specify presenting features. In cases that reported presenting features, there was a wide range of clinical features and symptoms. Clinical features of spinal cord compression were observed in 32 patients, although this was a small number compared to the number of cases in which the vertebral region was involved in EMH. The authors attribute this to the fact that the patients in the retrospective studies (n=182) had no symptoms of EMH. Lower extremity weakness, EMH site pain, and urinary incontinence were also reported (9%, 7.5%, and 1.18% of patients, respectively). Masses were found by examination or imaging in 4% of patients.
EMH was most commonly diagnosed by MRI (89.3% of cases), CT scans showing 9.9% of cases. In 9 patients (3.6%), a histopathological diagnosis was made. The most common treatment was blood transfusion to raise hemoglobin levels before transfusion, followed by radiation therapy, surgery, hydroxyurea, and steroids.
Currently, there are no clear guidelines regarding the management of EMH in TDT, although conservative management by blood transfusion appears to be the preferred option for patients with mild or no symptoms. Achieving sufficient pre-transfusion hemoglobin levels to avoid EMH is critical, and clinicians should be aware of the risk of EMH in patients who do not reach optimal levels, the authors noted.
“We found no studies comparing different treatment approaches and their outcomes in BTM patients who developed EMH. Our review found similar results (wherever results were reported) with conservative and invasive methods,” the authors wrote. “Therefore, it is imperative to study the effects of treatment options (non-invasive and invasive) prospectively so that physicians can have clear guidelines based on the best treatment options.”
Lack of outcome data in the studies in the review prevented statistical analysis of outcomes based on treatment strategy. However, the authors concluded that EMH represents an increasingly important complication of TDT and warrants further research in this population.
A Subahi E, Ata F, Choudry H, et al. Extramedullary hematopoiesis in patients with transfusion-dependent β-thalassemia (TDT): a systematic review. Anne-Med. Published online March 9, 2022. doi:10.1080/07853890.2022.2048065