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.