Myelodysplastic syndromes (MDS) are heterogeneous neoplastic diseases affecting elderly individuals although they can rarely affect younger individuals. Primary Immunodeficiencies Disorders (PIDs) are a group of congenital disorders often depicted in early age, associated with an increased susceptibility to infections, immune-dysregulation and a higher risk of malignancy.
We retrospectively examined a cohort of younger patients with MDS (2000-2018) to verify the frequency of genetic predisposition and recurrence of immune-dysregulation phenomena.
Fiftyfour consecutive patients < 60 years (median age 52) were analysed. Data were collected at time of first bone marrow examination, corresponding to diagnosis or at revaluation consequent to second opinion.
Autoimmune phenomena were present in 22.2% of patients, including arthritis, thyroiditis and dermatological manifestations. Although autoimmunity is more frequently associated to hypoplastic bone marrow, none of them presented hypoplastic-MDS. Immunodeficiency were discovered in 5 patients: a late onset of GATA-2 deficiency, two patients with PID-associated genetic disorders (Noonan syndrome and a case highly suggestive for congenital dyskeratosis) and a Combined Immunodeficiency (CD4penia and epidermodysplasia verruciformis-like syndrome). Moreover, 4 patients debuted with isolated neutropenia in young age, at least 10 years before MDS diagnosis: Whole Exome Sequencing on DNA of each patient is ongoing, in order to identify causative variants.
PIDs and early onset MDS could represent two features of unique congenital disorder, in which myeloid impairment in MDS is justified by loss of immune-surveillance or immune-dysregulation. Immunological assessment in young MDS is required, albeit idiopathic cytopenia in PID patient could demand a close follow-up in the risk of developing MDS.