Rare blood disease DBA: A comprehensive guide to treatment from drugs to genes

Author: Han Bing, Chief Physician, Peking Union Medical College Hospital

Reviewer: Jiang Qian, Chief Physician, Third Medical Center, PLA General Hospital

Congenital pure red cell aplasia (DBA) is a rare inherited blood disorder characterized by impaired red blood cell production, leading to severe anemia. The condition can be diagnosed in the neonatal period, and the severity of its clinical manifestations varies, ranging from mild anemia symptoms to severe anemia requiring blood transfusion to maintain life, so the treatment strategy needs to be customized according to the clinical manifestations.

Currently, glucocorticoids such as prednisone or dexamethasone are the first choice for the treatment of congenital pure red cell aplasia. These drugs promote erythropoiesis by regulating the function of the immune system. According to textbook recommendations, the initial dose is usually 2 mg/(kg·d), and the dose is gradually reduced after one to two months of continuous treatment. However, it should be noted that although glucocorticoids show good efficacy in most patients, some patients may still experience relapse or ineffectiveness.

Figure 1 Original copyright image, no permission to reprint

For patients who are ineffective or intolerant to glucocorticoid treatment, other treatment options can be considered. For example, patients with severe anemia may need long-term blood transfusions to maintain stable vital signs. However, long-term blood transfusions carry the risk of iron overload, which not only causes damage to the function of organs such as the liver and heart, but may also cause a series of serious complications, such as cirrhosis, heart failure, hypothyroidism, diabetes, and sexual dysfunction.

Therefore, iron removal therapy is needed to reduce the deposition of iron in the body. Iron removal therapy mainly uses iron removal drugs, such as deferasirox, to help patients metabolize excess iron and maintain ferritin levels below 1000ng/ml, thereby reducing complications caused by iron overload. However, iron removal therapy needs to be carried out for a long time, and the drug dosage and treatment plan need to be adjusted according to the patient's specific situation.

For some severe cases, allogeneic hematopoietic stem cell transplantation is considered a radical cure. Before transplantation, the donor must be screened thoroughly to exclude gene carriers, and siblings or unrelated donors are preferred. Although the transplantation success rate is high, it is usually only used in special circumstances due to its high cost and risks.

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In recent years, with the continuous progress of medical research, some emerging therapies such as Eltrombopag have gradually been introduced into the treatment of DBA. Eltrombopag is a thrombopoietin receptor agonist, originally used to treat diseases such as idiopathic thrombocytopenic purpura. However, at the 2017 American Society of Hematology Annual Meeting, it was reported that Eltrombopag has also achieved significant results in the treatment of hereditary congenital pure red cell aplasia. Although it is relatively expensive, it provides new hope for treatment for some patients.

As a frontier area of ​​DBA treatment, gene therapy is gradually moving towards clinical practice. Since DBA is mostly caused by mutations in specific genes such as RPS19, targeted gene repair can theoretically reverse the disease. However, given the differences in mutation points among different patients, developing personalized treatment plans is extremely challenging and is still in the research stage.

The prognosis of DBA patients is closely related to their clinical manifestations. For patients with mild symptoms, a good quality of life can be maintained through rational use of medication. However, severe patients face more challenges, such as growth retardation, organ damage, and increased risk of tumors. Regular monitoring and follow-up are the key to managing DBA, and a comprehensive examination every 3-6 months can help to adjust the treatment plan in a timely manner.