What question did this study set out to answer?

This research examines the relationship between therapeutic response to complement inhibitors and progression of bone marrow failure in PNH/AA patients.

December 8, 2025

Correlation between efficacy, clonal dynamics evolution, and development of bone marrow failure in PNH/AA syndrome treated with complement inhibitors: A single-center cohort study

Key Points

This research examines the relationship between therapeutic response to complement inhibitors and progression of bone marrow failure in PNH/AA patients.
Retrospective analysis of 92 PNH/AA patients treated with complement inhibitors.
Monitored parameters included clone size, next-generation sequencing, LDH levels, and hematologic response.
Follow-up duration was a median of 29 months.
89.1% of patients achieved hemolysis control but only 64.1% attained complete hematologic response.
17.4% experienced breakthrough hemolysis and 10.9% showed progression of bone marrow failure.
Significantly lower PNH clone size in progression group compared to stable group (76.2% vs. 91.3%, p=0.04).
New somatic mutations found in 20% of patients correlated with bone marrow failure (p=0.003).

Abstract

Abstract Objective: To investigate the correlation between therapeutic response patterns to complement inhibitors, clonal dynamics changes, and progression of bone marrow failure (BMF) in patients with PNH/AA (paroxysmal nocturnal hemoglobinuria/aplastic anemia). Methods: A retrospective analysis was conducted on 92 PNH/AA patients treated at our center from 2021 to 2025. All patients received complement inhibitor therapy (eculizumab, crovalimab, or iptacopan), with a median follow-up of 29 months. Parameters monitored included PNH clone size, next-generation sequencing (NGS), lactate dehydrogenase (LDH) levels, hematologic response, breakthrough hemolysis (BTH), and dynamic changes in hematopoietic function (reticulocytes, absolute neutrophil count, platelets). Outcomes related to bone marrow failure were assessed. Results: Treatment Response: 89.1% (82/92) of patients achieved hemolysis control, but only 64.1% (59/92) attained a complete hematologic response. BTH occurred in 17.4% (16/92). BMF Progression: 10.9% (10/92) showed signs of BMF progression. This correlated with residual hemolysis and discontinuation of immunosuppressive therapy (IST). The median PNH clone size was significantly lower in the progression group (76.2%) compared to the stable group (91.3%) (p=0.04). Clonal Dynamics: Patients with an expanding PNH clone had a 3.2-fold increased risk of BMF progression (95% CI 1.8–5.6). New somatic mutations were detected in 5 patients (20%), which showed a significant association with BMF (p=0.003). Conclusion: Complement inhibitors effectively control hemolysis in PNH/AA patients but provide limited improvement in BMF. Residual hemolysis, the emergence of new subclones, and an expanding PNH clone are associated with BMF progression. Timely combination therapy with immunosuppressive agents is warranted. Keywords: PNH, Bone Marrow Failure, Complement Inhibitors, Immunosuppressive Therapy

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Cite This Study

Bing Han (Mon,) studied this question.

synapsesocial.com/papers/69362f6c4fa91c937236e00c https://doi.org/https://doi.org/10.1182/blood-2025-4987

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