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. 2022 May;197(4):467-474.
doi: 10.1111/bjh.18091. Epub 2022 Feb 22.

Fanconi anaemia: A syndrome with distinct subgroups

Blanche P Alter  1 , Neelam Giri  1 , Lisa J McReynolds  1 , Burak Altintas  1
Affiliations

Fanconi anaemia: A syndrome with distinct subgroups

Blanche P Alter et al. Br J Haematol. 2022 May.

Abstract

Fanconi anaemia (FA) is an inherited bone marrow failure syndrome (IBMFS) with a high cancer predisposition rate. Traditional diagnoses are made before age 10 years due to bone marrow failure (BMF) and characteristic birth defects. Up to 10% of published cases were adults at diagnosis. We hypothesized that FA subgroups diagnosed in childhood are distinct from those diagnosed as adults. We classified patients by age at diagnosis of FA as FA-PED (<18 years) or FA-ADULT (≥18 years). The National Cancer Institute IBMFS cohort included 178 FA-PED and 26 FA-ADULT cases. We compared various features; the cumulative incidences of first adverse events (severe BMF leading to haematopoietic cell transplant or death, leukaemia, or solid tumours) were compared using competing-risk analyses. FA-ADULT lacked the 'typical' FA features (birth defects and early-onset BMF or leukaemia), were mainly female, had more patients with FANCA genotype, and had or developed more head and neck squamous-cell carcinoma (HNSCC) and/or gynaecological cancers compared with FA-PED, albeit at similar ages in both subgroups. FA-ADULT is a distinct subgroup that remained unrecognized during childhood. Centres for adult haematology-oncology should consider FA diagnosis in patients with early-onset HNSCC or gynaecological cancer with or without haematologic problems.

Keywords: Fanconi anaemia; cancer predisposition; gynaecological cancer; head and neck squamous-cell carcinoma; inherited bone marrow failure.

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Conflict of interest statement

Competing interests: The authors have no competing interests.

Figures

Figure 1:
Figure 1:
Age in years at diagnosis of FA in all Pediatric and Adult Patients, p <0.001. The two groups are separated by the arrow in 1A. A, Frequency of all cases. B, Box plots. Left, FA-PED. Right, FA-ADULT.
Figure 2:
Figure 2:
Cumulative incidence of solid tumors. Solid line, FA-PED. Dashed line, FA-ADULT (p= 0.24).
Figure 3:
Figure 3:
Age at diagnosis of head and neck squamous cell carcinoma (HNSCC) and Gynecological Cancers (GYN CA). A, Box plots of age in years at diagnosis of HNSCC. FA-PED vs FA-ADULT, p = 0.5. B, Cumulative incidence of HNSCC. C, Box plots of age in years at diagnosis of GYN CA in FA-PED and FA-ADULT, p = 0.3. D, Cumulative incidence of GYN CA.
Figure 4:
Figure 4:
Cumulative incidence of first adverse events, in competing risk analyses, Left, FA-PED. Right, FA-ADULT. Red, hematopoietic stem cell transplant or death from aplastic anemia (p = 0.0001 between FA-PED and FA-ADULT). Green, acute myeloid leukemia (AML; p = 0.21 between FA-PED and FA-ADULT). Blue, solid tumors (p = 0.025 between FA-PED and FA-ADULT). Shaded areas are the 95% confidence intervals.
Figure 5:
Figure 5:
Survival estimates for FA-PED and FA-ADULT. Solid red line, FA-PED. Dashed blue line, FA-ADULT. p = 0.01.
See this image and copyright information in PMC

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