Fanconi anemia and haploidentical stem cell transplantation

Abstract

Fanconi anemia (FA) is an autosomal recessive disorder belonging to chromosome instability syndromes. 1 It has a prevalence of 1 in 360 000 live births and is relatively common in areas with high consanguinity rates. 2 The clinical presentation is broad, varying from asymptomatic and phenotypically normal to dysmorphisms and severe pancytopenia. 3 Overall, hematologic abnormalities occur in at least 90% of patients, with a median of onset at 7 years of age. Besides, these patients have a greater predisposition to developing acute myeloid leukemia and solid tumors. 4,5 Hematopoietic stem cell transplantation is the only treatment with the potential to restore normal hematopoiesis in these patients, especially from a related donor with matched HLA has been associated with excellent results. 6 However, transplantation with post-transplant cyclophosphamide (CY) has recently become an alternative transplant strategy for non-malignant and malignant diseases that do not have a fully matched donor. 7,8 Patients with FA are a particularly suitable group for haploidentical stem cell transplantation (HSCT). Without HSCT, the prognosis is poor due to the advancement of bone marrow failure over the years and increased incidence of neoplasms. Nevertheless, DNA repair defects in these patients make them extremely sensitive to alkylating agents and, therefore, the dose of CY in this population must be modified to reduce toxicity risk. 9 Some studies have demonstrated that a total dosage of up to 60 mg/kg is safe in patients with FA. 10 Evidence of the viability of using haploidentical donors in FA has increased in recent years with excellent results. [11][12][13][14]