Overview

Background

Congenital Dyserythropoietic Anemia (CDA) is a group of rare hereditary blood disorders characterized by ineffective erythropoiesis, leading to chronic anemia and organ damage. Current treatment options are very limited, mainly relying on regular blood transfusions, which can cause severe complications over time. Our laboratory research and animal models suggest that Zoledronic acid, a medication commonly used for bone health, may improve ineffective erythropoiesis.

Purpose

The purpose of this exploratory study is to evaluate the efficacy and safety of Zoledronic acid in adult patients with CDA who do not have other effective treatment options. The primary goal is to see if this treatment can increase hemoglobin levels and reduce the need for blood transfusions.

Study Design:

This is a prospective, single-center, single-arm study. Participants will receive an initial intravenous dose (4 mg) of Zoledronic acid. After a 4-week observation period to ensure safety, participants will receive additional doses every 4 weeks for a total of 4 doses. Researchers will monitor hemoglobin levels, transfusion frequency, spleen size, and overall quality of life over a period of 12 to 24 weeks.

Eligibility

Inclusion Criteria:

• Age ≥ 18 years, regardless of gender.
• Diagnosis of Congenital Dyserythropoietic Anemia (CDA) based on clinical presentation, laboratory tests, and family investigation, with the presence of RBM28 mutation and/or increased vacuolization within nucleated red blood cells under light microscopy of bone marrow.
• Presence of anemia (Hemoglobin \< 100 g/L at screening) or transfusion dependence (defined as an average transfusion interval of \< 8 weeks within the past 3 months).
• Performance status is acceptable (ECOG score 0-2).
• Normal renal function (estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73m²).
• Serum calcium levels within the normal range.
• Female patients of childbearing potential must have a negative pregnancy test before enrollment and agree to use effective contraception during the study and for 3 months after completion.
• The patient and/or guardian voluntarily sign the informed consent form.

Exclusion Criteria:

• Known hypersensitivity to bisphosphonates or any of their excipients.
• Severe periodontal disease or a recent history (within 6 months) of osteonecrosis of the jaw.
• Hypocalcemia.
• Pregnant or lactating women.
• Currently receiving other experimental drug treatments that may affect erythropoiesis (e.g., Luspatercept).
• Active, uncontrolled systemic infection.
• Severe cardiac, pulmonary, or hepatic dysfunction, as judged by the investigator to be unsuitable for participation in the study