Box 1: Real-world FA patient
examples
Patient 1: Diagnosed with FA at age 4 due to bone marrow
failure and was transplanted with the bone marrow of his sister.
Clinically, no signs for graft versus host disease (GvHD) had been
observed but severe viral reactivation complicated the clinical course.
He was treated both with anti-viral and immunosuppressive medication.
Patient started to drink alcohol at a social occasion at age 18. A
visible lesion developed at age 22 at the gingiva and was biopsied
revealing moderate dysplasia. Since then, the patient stopped drinking.
Patient 2: Diagnosed with FA at age 6. Additionally, he was a
carrier of an inherited mutation in the APC (APC regulator of WNT
signaling pathway) gene. At age 8, the patient needed hematopoietic stem
cell transplantation due to bone marrow failure. Unfortunately, he
developed severe GvHD. At age 16, he was diagnosed with oral candida
infection in a lesion at the gingiva. Due to persistence of the lesion,
it was biopsied and the diagnosis of SCC was made. After local excision
with clear margins, the patient developed three months later a local
soft tissue metastasis. Further treatment including radiation and CD274
blockage were not able to save the patient and he deceased at age 19.
Patient 3: Diagnosed with FA at age 6 due to bone marrow
failure. She was treated with anabolic steroids after a period of
transfusions and severe infection. The treatment brought the blood
counts up but due to the development of clonal hematopoiesis with
pre-leukemia, she was transplanted at age 16. At age 21, an oral lesion
at the tongue developed and the diagnosis of a candida infection was
made. However, after initial treatment, the lesion came back showing
signs of inflammation. Due to persistence of the patient, a biopsy was
done at age 23 and a severe dysplasia was diagnosed.
Patient 4: Started social drinking and smoking at least one
pack a day at age of 16. At age 20, a small lesion at the right side of
the tongue was noticed by the patient. Clinical diagnosis of a local
inflammation was made and the patient was treated over two months with
immune suppression. Because there was no clinical benefit from the
treatment, the patient stopped the medication on their own. Due to
growing of the lesion and development of pain, eventually a biopsy was
performed, confirming the diagnosis of T1 stage SCC at age 21. Due to
the unusual age at presentation, investigations revealed the underlying
FA diagnosis. Patient was treated with local excision.
Patient 5: Diagnosed with FA at age 8 and directly
transplanted. Mild GvHD was clinically present. At age 28, an oral
lesion at the gingiva developed. An infection with candida was diagnosed
but the patient did not get any further treatment. At age 29, the lesion
was biopsied due to increase in size. Histologically, a high-grade
dysplasia and an invasive candida infection were seen.