後天性赤芽球癆

We describe a patient with long-standing rheumatoid arthritis (RA) who developed severe refractory transfusion-dependent anaemia lasting several months following treatment with a JAK1 inhibitor (Filgotinib). The patient proceeded with extensive investigations, including bone marrow assessment, and was initially diagnosed with Filgotinib-associated anaemia. However, despite stopping this agent, the anaemia persisted with fluctuating reticulocyte count resulting in multiple hospital admissions. Although the anaemia was initially attributed to Filgotinib, its persistence alongside delayed reticulocytopenia, ultimately led to a diagnosis of acquired Pure Red Cell Aplasia more than 12 months later. Complete remission was achieved with prednisolone + ciclosporin A. This case underscores the need to consider PRCA in RA patients on JAK inhibitors even with initially normal reticulocyte counts, as these agents may transiently mask underlying aplasia.

Acquired pure red cell aplasia (PRCA) is a bone marrow failure syndrome characterized by anemia, reticulocytopenia, and erythroid hypoplasia in the marrow that mostly affects older adults. Underlying T-cell dysregulation, often associated with clonality and/or STAT3 mutation among CD8+T-cells, provides a rationale for directed immunosuppressive therapies such as cyclosporin in the three most frequent disease subtypes: thymoma-associated PRCA, large granular lymphocytic leukemia-associated PRCA, and idiopathic PRCA. Some retrospective studies have demonstrated the significance of maintenance therapy for avoiding blood transfusion dependency, which is associated with poorer prognosis in patients with PRCA. While treatment options are currently scarce for patients with relapsed or refractory disease after CsA, results of a prospective randomized controlled clinical trial of sirolimus are expected in the near future.

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.

Acquired pure red cell aplasia (aPRCA) is rare and challenging to treat. We investigated the efficacy and safety of sirolimus plus roxadustat in patients with aPRCA (Chinese Clinical Trial Register number, ChiCTR2200065107). We enrolled 82 patients with aPRCA in this prospective single-arm, open-label, multicenter trial between October 2022 and January 2024. Treatment response and safety files were evaluated. The median age was 63 years. Seven patients withdrew during the trial period. Sirolimus plus roxadustat produced an overall response (OR) in 65 patients (90.3%) 3 months after initiation, which included a complete response (CR) in 39 (54.2%) and a partial response in 26 (36.1%). The 3-month CR rate was significantly higher in the newly diagnosed group (65.9% vs. 38.7%; P = 0.022). The 6-month OR rate in the entire cohort was 93.0% (CR, 77.5%; PR, 15.5%). The mean hemoglobin concentration increased from 5.5 ± 1.6 g/dL at baseline to 11.6 ± 2.5 g/dL after 6 months of treatment. The proportions of patients who achieved transfusion independence within 1, 2, and 3 months of treatment were 57.4%, 76.6%, and 89.5%, respectively. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale score and SF-36 survey score significantly improved after treatment. Treatment-related adverse events occurred in 24 patients (29.2%), and four events (4.9%) were grade ≥3. Sirolimus plus roxadustat is a promising treatment for aPRCA and has an acceptable safety profile, which warrants further investigation in a randomized setting.