Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia

Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia

Prospective interventional open-label non-randomized controlled trial to assess safety and efficacy of metformin in treating cytopenia in children and adolescents with Fanconi Anemia.

Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure, cancer susceptibility, and developmental abnormalities. Allogeneic hematopoietic stem cell transplantation offers curative therapy for hematologic complications of FA.

Oxymetholone is commonly used in the management of FA as it improves blood counts, red cells, and platelets. However, its use is limited by its high toxicity profile.

Metformin is a potential agent that reduces levels of both chromosomal radials and breaks in FA cells and increases the size of the hematopoietic stem cell compartment thus reducing cytopenia in patients with FA.

Inclusion Criteria:

• Age: 5 to 18 years
• Patients who are diagnosed with Fanconi anemia based on clinical features and confirmed by increased chromosomal breakage on diepoxybutane (DEB) stress testing.
• Presence of cytopenia (at least one of the following: hemoglobin (Hb) < 10 g/dL, platelet count < 100 x 109/L, or an absolute neutrophil count (ANC) < 1.0 x 109/L
• Patients receiving other therapies e.g., androgens are eligible for enrollment after a one-month washout period before the start of metformin.

Exclusion Criteria:

• Patients who underwent bone marrow transplantation.
• Patients with evidence of myelodysplasia, leukemia, or other concurrent malignancy.
• Patients who have a history of allergic reactions to metformin or similar compounds.
• Patients with a history of symptomatic hypoglycemia over the past year or hypoglycemia < 50 mg/dL on screening and baseline laboratory assessments.
• Patients with type 1 diabetes mellitus.
• Patients with vitamin B12 deficiency.
• Patients with Glucose-6-Phosphate Dehydrogenase deficiency.
• Patients with abnormal Kidney function tests including serum creatinine, elevated liver function tests including live enzymes (ALT or AST > 135 U/L, total bilirubin > 1.5 x upper limit of normal for age, and/or patients with metabolic acidosis (bicarbonate < 17 meq/L on venous blood gases).