Clinical Heterogeneity and Outcome of acquired PRCA: a Multicenter European Study

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.

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Journal
Blood Advances
Published
2026-05-27
DOI
https://doi.org/10.1182/bloodadvances.2025019525
Primary Topic
Blood groups and transfusion
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article
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article

Clinical Heterogeneity and Outcome of acquired PRCA: a Multicenter European Study

Sabrina Giammarco, Marta Bortolotti, C Clissa, María Argüello Marina et al.
Blood Advances
Blood groups and transfusion
article

Clinical Heterogeneity and Outcome of acquired PRCA: a Multicenter European Study

Sabrina Giammarco, Marta Bortolotti, C Clissa, María Argüello Marina, Giorgio Alberto Croci, Roochi Trikha, Mara Memoli, Mariasanta Napolitano, Francesco Versino, Giacinto Luca Pedone, Shreyans Gandhi, M. Hemmer, Omar Racchi, Salvador Payán‐Pernía, Margarita Jiménez‐Jambrina, Gabriele Merati, Sukanya Gogoi, Aparna Chitharanjan, Maria Teresa Lupo-Stanghellini, Jennifer Vidler, Bruno Fattizzo, Yamuna Wasanthi Wickramasinghe, Manujasri Wimalachandra, Tomas Jose Gonzalez-Lopez, Marc Michel, Austin G Kulasekararaj, Andreas Glenthøj, Wilma Barcellini, Francesco Passamonti, Antonio Palma-Vallelano, Filippo Brioschi
article en

Abstract

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.

Blood Advances
University of Verona (IT), Vita-Salute San Raffaele University (IT), University of Milan (IT), University of Moratuwa (LK), Agostino Gemelli University Polyclinic (IT), Copenhagen University Hospital (DK), Rigshospitalet (DK), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Ospedale Maggiore (IT), Hospital Universitario de Guadalajara (ES), Department of Health (ES), Azienda Ospedaliera San Gerardo (IT), King's College Hospital NHS Foundation Trust (GB), Alessandro Manzoni Hospital (IT), Hospital Universitario de Burgos (ES), Federico II University Hospital (IT), Hospital Juan Ramón Jiménez (ES), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Hospital Universitario Virgen del Rocío (ES), King's College Hospital (GB), Villa Torri Hospital (IT), Aziende Socio Sanitarie Territoriali di Lecco, University of Palermo (IT)
Good health and well-being
Openalex Percentile: Top 8%
Blood groups and transfusion
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