What is the life expectancy of individuals with Fanconi anemia?

Life Expectancy in Fanconi Anemia

The median survival age for individuals with Fanconi anemia is approximately 29 years, with survival rates of 91% at age 10,72% at age 20, and 47% at age 30 years. 1

Disease Overview and Survival Factors

Fanconi anemia (FA) is a genetically and phenotypically diverse syndrome characterized by DNA damage repair defects, bone marrow failure (BMF), and cancer predisposition. It is caused by biallelic mutations in one of at least 19 genes involved in DNA damage repair.

Key factors affecting survival include:

• Age at diagnosis: Younger age at time of intervention is associated with better outcomes 2
• Treatment with hematopoietic stem cell transplantation (HSCT): Significantly improves survival in appropriate candidates
• Development of malignancies: Major cause of mortality, especially after age 20
• Bone marrow failure: Approximately 40% develop severe BMF by age 20 and 50% by age 50 3

Major Causes of Mortality

1. Bone marrow failure complications:

   • Progressive cytopenias leading to infections and bleeding
   • Development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)

2. Malignancies:

   • Head and neck squamous cell carcinoma (HNSCC) - most common solid tumor
   • Cumulative incidence of solid/hematological malignancy reaches 51.7% by age 40 1
   • Risk of solid tumors and AML by age 50 is estimated at 30% and 10%, respectively 3

3. Transplant-related complications:

   • Infections
   • Chronic graft-versus-host disease
   • Secondary malignancies post-transplant

Survival Outcomes Based on Treatment

With HSCT:

• Two-year survival probability: 66% with HLA-identical siblings, 29% with alternative donors 2
• 10-year and 15-year survival probabilities: 90% and 79%, respectively 4
• Factors improving HSCT outcomes:
  • Younger age
  • Higher pre-transplant platelet counts
  • Use of antithymocyte globulin
  • Low-dose cyclophosphamide plus limited field irradiation 2

Without HSCT:

• A subset of patients with stable cytopenia can survive into adulthood without HSCT 1
• These patients require tight monitoring for worsening hematopoietic function and cancer occurrence

Long-term Complications in Survivors

1. Endocrine abnormalities:

   • Hypothyroidism (42%)
   • Diabetes (10%)
   • Low body mass index (31%)
   • Low bone mineral density (51%) 5

2. Malignancies:

   • HNSCC risk increases significantly after age 20
   • Risk is higher in those who received HSCT (hazard ratio 2.9) 1

3. Quality of life:

   • Among adult survivors, the majority are employed (52%) or full-time students (13%) 5

Surveillance Recommendations

For optimal outcomes and early detection of complications:

• Complete blood counts and bone marrow evaluation at least annually 3
• Monthly oral self-examinations and biannual dental examinations 3
• Annual HNSCC evaluation by an otolaryngologist beginning in early adolescence 3
• Annual gynecologic examination for women starting in adolescence 3
• Baseline pulmonary function tests and endocrine evaluation 3

Treatment Considerations

• HSCT is potentially curative for bone marrow failure 3
• Androgen therapy may be tried for bone marrow failure in patients not undergoing HSCT 6
• Cancer-specific therapy with avoidance of DNA-damaging agents 3
• Supportive care for other complications

The improvement in survival outcomes over recent decades highlights the importance of early diagnosis, appropriate intervention timing, and comprehensive surveillance for complications in managing Fanconi anemia.