Xinru Jia

Background: Cyclosporine A (CsA) is the standard first-line treatment for acquired pure red cell aplasia (PRCA), but outcomes vary. Effective salvage strategies for CsA-refractory patients, particularly those with complex secondary subtypes, remain inadequately defined. Additionally, the clinical utility of STAT3/5b mutations in guiding treatment selection remains unclear. Objectives: To evaluate the efficacy of second-line sirolimus for the treatment of PRCA and explore the possible genetic predictors for the response. Design: This study was a retrospective, single center, comparative study. Methods: Patients with acquired PRCA treated between 2021 and 2025, including 36 patients who received first-line CsA and 22 patients who switched to sirolimus due to lack of response or intolerance. Clinical outcomes, including overall response rate (ORR) and time to response (TTR), were compared between primary and secondary PRCA. STAT3/5b mutation status was also analyzed to assess its predictive value for treatment response. Results: The ORR for first-line CsA was 25.0% (9/36), with significantly higher efficacy observed in primary cases (42.1%, 8/19) than in secondary cases (5.9%, 1/17; p = 0.015). In the salvage sirolimus group, the ORR was 54.5%, demonstrating efficacy in both primary (37.5%, 3/8) and secondary cases (64.3%, 9/14). The median TTR did not differ significantly between sirolimus and CsA (3.0 vs. 1.5 months, p = 0.150), and both agents achieved sustained remission in responders. Regarding genetic predictors, no responses to CsA were observed in patients harboring STAT3/5b mutations (0/6). In contrast, sirolimus elicited responses in both mutated (3/6) and wild-type (4/5) patients, indicating efficacy irrespective of STAT3/5b status. Conclusions: CsA is effective in primary PRCA, whereas sirolimus demonstrates efficacy in both primary and secondary cases regardless of STAT3/5b status. Early genetic profiling may facilitate the identification of patients who may not fully response to CsA and potentially earlier transition to sirolimus salvage therapy.

Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that have been increasingly defined and characterized over the past two decades, known for their remarkable capacity to expand and exert immunosuppressive effects in various pathological contexts, such as malignancies, infections, and inflammatory diseases. Although MDSCs have attracted significant attention in tumor immunology, their multifaceted roles in immune‐mediated hematological disorders remain comparatively understudied and less understood, especially in contrast to their well‐documented functions in both solid and hematological malignancies. This review delves into the biological characteristics and functional mechanisms of MDSCs, as well as their dual immunomodulatory roles in various immune‐mediated hematological disorders such as immune thrombocytopenia and aplastic anemia. Substantial evidence indicates that in these diseases, the expansion, recruitment, and function of MDSCs are significantly altered, with their levels closely correlated to disease activity. Based on these findings, we further explore the therapeutic potential of targeting MDSCs. Manipulating MDSCs offers a pioneering perspective for the development of next‐generation immunotherapies, which holds promise for reshaping the current treatment landscape of immune‐mediated hematological disorders.