Pure red cell aplasia (PRCA) is a rare single lineage bone marrow failure defined by anemia with profound reticulocytopenia and severe reduction of erythroid precursors. Clinical spectrum is heterogeneous, and diagnosis often requires extensive evaluation to distinguish primary from secondary causes such as thymoma, autoimmune diseases, T-LGL expansion and MDS, with which differential diagnosis is particularly challening. Evidence guiding management remains limited due to the rarity of the disease and the lack of prospective studies. We conducted a multicenter retrospective analysis of 121 acquired adult PRCA (excluding PVB19-associated PRCA) cases across 14 European centers. Secondary forms accounted for 78% of cases, mostly thymoma (23%) or MDS (21%). In a subset of patients, BM immunohistochemistry demonstrated significant depositions of C3, C4d, IgM, IgG, reducing after immunosuppression. NGS was performed in half of patients 36% of which presented mutations predominantly related to clonal hematopoiesis, except in MDS-associated cases which often carried multiple non-CH mutations. Immunosuppression represented the backbone of therapy: cyclosporine A (CyA) was the most effective agent, with 61% ORR (47% complete) and better outcomes when initiated earlier; mTOR inhibitors showed promising activity as second-line therapy, with responses in 71% of patients, including CyA-refractory cases. Mortality reached 30%, predominantly due to infectious complications, and was significantly higher in MDS-associated cases. PRCA remains a diagnostically challenging and clinically heterogeneous disorder in which integration of molecular analyses may refine diagnostic accuracy and patient stratification. Immunosuppression remains the mainstay of treatment, with CyA being a reliable first-line and mTORi emerging as encouraging rescue options.
Versino et al. (Wed,) studied this question.