Incidence of malignancy and clonal chromosomal abnormalities in Fanconi anemia

Background: Fanconi anemia (FA) is an autosomal recessive, cancer susceptibility disorder characterized by diverse clinical features, such as short stature, skeletal or skin abnormalities, progressive bone marrow (BM) failure, and increased risk of malignancies. Clonal chromosomal abnormalities are frequently reported in FA patients transformed to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aim: To study the incidence of malignancy and clonal chromosomal abnormalities in FA patients. Materials and Methods: Thirty-eight clinically diagnosed FA patients were studied at the time of diagnosis and the patients were followed-up for a maximum of 28 months at 3-month intervals. The median duration of follow-up of these patients was 19.8 months. Chromosomal breakage investigation using mitomycin C (MMC)- and diepoxybutane (DEB)-induced peripheral blood cultures were stimulated with phytohemagglutinin. Cytogenetic study was done on the BM cells to detect clonal chromosomal aberrations. Results: Eleven (28.95%) out of 38 patients developed malignancies, including 6 (54.54%) MDS, 4 (36.36%) AML, and 1 (2.63%) squamous cell carcinoma. The clonal chromosomal abnormalities were detected in 5 (45.45%) FA patients who developed malignancies and the type of chromosomal abnormality detected were monosomies 5, 7, trisomy 10, dup(1)(q12-q24), and inv(7)(p11pter). Conclusion: The FA patients have a high risk of developing malignancies, and clonal chromosomal abnormalities play an important role in the prognosis of the disease. Therefore, FA patients need to be followed-up at regular intervals for early diagnosis and optimal management of the disease