From the Guidelines
Fanconi anemia patients should undergo regular cancer surveillance, including skin examinations, gynecologic exams for females, and oral cancer screening, due to their significantly increased risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors, particularly head and neck, esophageal, and gynecological cancers, as reported in a recent study published in 2024 1. The management of Fanconi anemia involves a multidisciplinary approach, focusing on supportive care, monitoring, and prevention of complications.
- Regular blood count monitoring is essential to detect progressive pancytopenia, which is a common feature of bone marrow failure in these patients.
- Supportive care with transfusions, as needed, can help manage anemia, neutropenia, and thrombocytopenia.
- Hematopoietic stem cell transplantation is currently the only curative treatment for bone marrow failure in Fanconi anemia patients.
- Androgens, such as oxymetholone, and growth factors, like G-CSF, may be used to temporarily improve blood counts, particularly in patients with severe cytopenias.
- Genetic counseling is crucial for families, as Fanconi anemia is typically inherited in an autosomal recessive pattern, although X-linked and dominant forms exist, with mutations in at least 21 different genes involved in DNA repair, particularly the FA pathway that repairs DNA crosslinks 1. The risk of developing cancer in Fanconi anemia patients is significantly higher than in the general population, with a cumulative incidence of malignancies by age 50 estimated to be around 50% for myelodysplastic syndrome and leukemia, and 20-30% for solid tumors, including head and neck squamous cell carcinoma, which tends to develop at a younger age in these patients 1.
From the Research
Definition and Characteristics of Fanconi Anemia
- Fanconi anemia (FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity, and extreme cancer predisposition 2.
- It is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers 3.
- FA is characterized by progressive bone marrow failure, increased susceptibility to leukemia and cancer, and genomic instabilities 4.
Clinical Management and Treatment
- Bone marrow transplantation is an effective treatment for Fanconi anemia, with HLA-identical sibling transplants showing better outcomes than alternative donor transplants 3.
- Factors associated with increased survival after bone marrow transplantation include younger patient age, higher pretransplant platelet counts, use of antithymocyte globulin, and use of low-dose cyclophosphamide plus limited field irradiation 3.
- Current and future therapies for FA are being developed, with a focus on understanding the molecular basis of the disease 5.
Molecular Pathogenesis
- FA is a DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging 6.
- The FA gene products are involved in interstrand cross-link (ICL) repair, and defects in this pathway contribute to the development of bone marrow failure and cancer 6, 4.
- Altered epigenetic regulation, telomere defects, and elevated levels of inflammatory mediators also play a role in the pathogenesis of FA 6.