Fanconi anemia in the Czech Republic: Role of HSCT and long-term follow-up

Abstract

Fanconi anemia (FA) is a rare and heterogeneous syndrome associated with bone marrow failure and increased risk of cancer. While FA is often characterized by the presence of congenital malformations, in some patients cytopenia may be the only sign. In our cohort diagnosis was based on evidence of increased chromosome fragility with subsequent confirmation by gene mutation detection. Methods Our cohort includes 35 probands diagnosed with FA aged 0-24.3 (median 6) years between January 1986 and August 2020. Congenital anomalies at diagnosis were seen in 5 and cytopenia in 22 patients, 8 patients had family history of FA. Genetic test confirmed FANCA gene mutations in 24, FANCG in 3, FANCD1 in 4, and FANCB in 2 siblings. Results During follow-up 7 patients developed malignancy (among them all 4 patients with FANCD1 mutation). Seventeen patients developed marrow failure, for which 15 patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the median age of 9.3 (4.6-24.3) years. All transplanted patients achieved stable hematopoietic engraftment. However, in 2 patients due to inadequate immune reconstitution developed fatal CMV pneumonia and invasive aspergillosis 12 and 14 months post HSCT, accordingly. In one patient we have diagnosed adenocarcinoma of the gut 10 years and squamous cell carcinoma of tongue 13 years after HSCT. Thirteen patients are alive with a median follow-up of 10.6 (0.3 - 15.1 years) years after HSCT. With a median follow-up till the last visit of 12.6 (0.2-34.4) years 28/35 (80%) patients are alive, 4 died of malignancy, 2 died due to HSCT-related complications, and one due to severe congenital somatic defects. Conclusions HSCT is effective in FA patients with bone marrow failure and prevents further development of hematological malignancies. A lifelong and careful multidisciplinary follow-up of patients with FA is essential for early detection of bone marrow failure or any malignant disease.