Israeli Fanconi Anemia Registry

Abstract Using epidemiological data from retrospective cohorts of patients with Fanconi Anemia (FA) in North America and Germany a quantitative model to estimate bone marrow failure (BMF) and cancer risk was previously generated. To evaluate generalizability to another population, and to determine the risks for adverse outcomes in Israel, we created an Israeli FA registry and used the model to evaluate complications. We reviewed patient charts of 66 patients with FA diagnosed in Israel between 1964–2005. The data base included demographic information, as well as data describing the congenital abnormalities, FA complementation groups, BMT course and malignancies. Thirty six (36) patients were of Jewish origin [Ashkenzi 7, Sephardic 23, mixed 6] and 30 of Arabic origin. The first adverse event was bone marrow failure (BMF) in 35 patients (53%), hematological malignancy in 7 (11%) and 2 solid tumors in each of 3 patients (5%). The cause-specific hazard of BMF peaked at 10.5%/year at age 10 years (95% CI: 6.7–14.1%/year). The hazard of AML/ALL and MDS were stable at 0.9%/year (95% CI: 0.42–1.85%/year) and 1.4%/year (95% CI: 0.76–2.49%/year) respectively. The cumulative incidence of each outcome to age 32 was 70% for BMF, 13% for AML/ALL, and 17% for solid tumor. A five item congenital abnormality score was significantly associated with the risk of BMF (P = 0.009). The ratio of observed to expected cancer was 71 for all cancers [50 for solid tumors, 175 for leukemia] and >11,000 for myelodysplastic syndrome. Significantly elevated ratios of observed to expected cancers were observed for head and neck squamous cell carcinoma in 2 patients (986-fold), tumor of larynx (13,238-fold), vulva (3,701-fold), cervix (244-fold) and breast (88-fold). The complementation group was known in 41 patients [A 25 (63%), C 9 (22%), G 6 (15%), and D1 1 (2%)]. However, associations between complementation groups and specific outcomes were not significant. Despite the different ethnic background and the smaller number of FA patients in the Israeli cohort the risk estimates compared with the US and German cohorts were similar. As previously suggested the congenital abnormality score was significantly associated with the risk of BMF; an extraordinary risk of developing AML/MDS and later specific solid tumors was also found.