PF352 TUNISIAN FANCONI ANEMIA REGISTRY (TFAR) REPORT, THE 2018 UPDATE

Abstract

Background:Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease. Many groups have established FA registers. In Tunisia, we created, in collaboration with the Tunisian Fanconi Anemia Study Group (TFASG), the Tunisian Fanconi Anemia Registry (TFAR), already initiated in 1998, by retro and prospective registration of FA. The first report was published in 2012.Aims:We present here the update of Tunisan Fanconi Anemia Registry on 2018.Methods:All hematology and pediatrics departments include their FA patients diagnosed between January 1983 and April 2018. The diagnosis was based on the following criteria: before 1998, a progressive bone marrow failure, the malfomative syndrome (IFAR score greater than 2), spontaneous chromosomal instability +/‐ family history of FA. After 1998, it is based on chromosomal instability on exposure to mitomycin C (MMC) greater than 70% of mitoses. We analyzed epidemiological, clinical, biological features, treatment and evolution of the 232 patients included until 2018.Results:232 patients belonging to 157 families were included. The annual incidence was 6 cases / year. The mean age at diagnosis was 10 years 6 months, the median was 9 years (extreme: prenatal diagnosis to 41 years). The Geographic distribution shows predominance in the south and center of Tunisia (38% each) compared to the north (24%). The circumstances of discovery were anemic syndrome in 63% of patients, bleeding syndrome in 37% of patients, acute leukemia in 2% cancer in 0.8% of patients, and family survey in 9.5% of patients. There was consanguinity in 80%. Malformative syndrome in 78%: stature ponderal retardation in 71%, « café au lait » spots in 72%, facial dysmorphy in 85%, bone malformations 53%, thumb column anomalies 37% and renal malformations 57%. Pancytopenia at diagnosis was found in 56%: Thrombocypenia is the most constant hematologic anomaly 96%, anemia in 80% and leuconeutropenia is found in 73%. Elevation of fetal hemoglobin is found in 91% of cases.Among 232 patients, 58 patients have been allo grafted from matched geno identical donors: 56 brodherhood, 1 fadher and 1 grand fadher 68% of patients with donor. Five patients without geno identical donor, have been allografted: from pheno identical donors in four cases in France and one from phenoidentical cord blood in Germany.Androgen treatment was given in 141 mainly Norethandrolone. 79% of those patients were good responders at 12 months. Evolution to a myelodysplastic syndrome is observed in 26 patients 11% and to acute leukemia in 26 patients 11%: 21 AML and 5 ALL. Seven cancers is diagnosed in 6 patients 2.5%. The median survival age in all patients is 14 years 3 months, it is significantly better in allo grafted patients (19 years vs 13 years 6 months, p < 0.00001). All cases of acute leukemia and cancer have died.Summary/Conclusion:FA seems frequent in Tunisia, which is in part explained by the high consanguinity and endogamy in our country. It is often severe or moderate and requires androgen treatment or bone marrow transplantation. It must concern all patients with matched related donor. We have not access to cord blood bank or international file of volunteer bone marrow donors to do phenoidentical allograft. We project to introduce the haplo identical related donor allograft for FA patients. All patients with solid tumor or acute leukemia have died. We must do prevention and early detection of cancer.