Review: More Research on Treatment for Extramedullary Hematopoiesis in Transfusion-Dependent Beta Thalassemia Is Needed

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 a significant clinical complication in transfusion-dependent BT (TDT) and warrants prospective studies on optimal treatment strategies.

BT, a condition characterized by reduced production of the beta-globin chain of hemoglobin, is estimated to occur in up to 5% of the global population. Depending on clinical characteristics, BT can be stratified into 2 main types: thalassemia major (TM) and thalassemia intermedia (TI). Patients with TM typically depend on regular blood transfusions, whereas those with TI are non–transfusion dependent (NTDT). EMH, a rare complication of BT and other hematological conditions, occurs when blood cells develop in locations outside of the bone marrow in response to reduced production within the marrow. EMH is reported in up to 20% of patients with NTDT vs less than 1% of patients with TDT.

“Treatment options for thalassemia patients with EMH depend on the location and mass effect symptom, including hyper transfusion, surgical excision, radiotherapy, hydroxyurea, or various combinations of therapy,” the authors wrote. “The main aim of this review is to pool all the available data on the presentations and management of EMH in the context of TDT, providing summary statistics.”

A literature search returned 253 reported cases of EMH in patients with TM, encompassing 2 retrospective studies and 70 case reports. The mean age at EMH presentation was 35 years, and the spinal cord was the most commonly involved site of EMH (87.7% of cases).

Most cases (72%), including those in the retrospective studies, did not specify the presenting features. In cases that did report on presenting features, there was a wide range of clinical features and symptoms. The clinical features of spinal cord compression were seen in 32 patients, although this was a small number relative to the number of cases in which the spinal area was involved in EMH. The authors attribute this to the fact that patients in the retrospective studies (n = 182) did not have symptoms of EMH. Lower-limb weakness, pain at the site of EMH, and urinary incontinence were also reported (9%, 7.5%, and 1.18% of patients, respectively). Masses were found via examination or imaging in 4% of patients.

EMH was most commonly diagnosed by MRI (89.3% of cases), with CT scans showing 9.9% of cases. In 9 patients (3.6%), histopathological diagnosis was made. The most common treatment was blood transfusion to increase pretransfusion hemoglobin levels, followed by radiation therapy, surgery, hydroxyurea, and steroids.

Currently, there are no clear guidelines regarding EMH management in TDT, although conservative management through blood transfusions appears to be the preferred option for patients with mild or no symptoms. Achieving sufficient pretransfusion hemoglobin levels to avoid EMH is key, and clinicians should be aware of the risk of EMH in patients who do not reach optimal levels, the authors noted.

“We could not find any study comparing different therapeutic approaches and their outcomes in BTM patients who developed EMH. Our review found similar results (wherever outcomes were reported) with conservative and invasive methods,” the authors wrote. “Therefore, it is imperative to study the effects of the treatment options (non-invasive and invasive) prospectively so physicians may have clear guidelines based on the best treatment options.”

The lack of data on outcomes in the studies within the review prevented a statistical analysis of outcomes based on treatment strategy. However, the authors concluded that EMH represents an increasingly significant complication in TDT and warrants further research in this population.

Reference

A Subahi E, Ata F, Choudry H, et al. Extramedullary haematopoiesis in patients with transfusion dependent β-thalassaemia (TDT): a systematic review. Ann Med. Published online March 9, 2022. doi:10.1080/07853890.2022.2048065