PNH Clones for Aplastic Anemia with Immunosuppressive Therapy: A Systematic Review and Meta-Analysis

Objectives: PNH clones, also aptly called “escape clones,” are evidence of acquired immune-mediated bone marrow failure and have a high prevalence in patients with aplastic anemia (AA). Several studies have reported contradictory results regarding the impact of PNH clones on AA patients with immunosuppression treatment, and PNH clones have not been confirmed as positive predictors of response in the AA guidelines of the British Society for Standards in Haematology. Methods: We performed a meta-analysis to address this issue by searching for articles in PubMed, EMBASE, The Cochrane Library, Web of Science, and ClinicalTrials.gov, and for abstracts from the annual meetings of the American Society of Hematology and the European Hematology Association. We included 1,236 participants from 11 cohort-controlled studies. Our primary outcome was the 6-month hematologic response with a secondary outcome of the mortality rate within 3 months. Results: A better response rate was observed in the PNH+ group than in the PNH– group (odds ratio [OR] 2.85; 95% confidence interval [CI] 2.17–3.75; p < 0.00001), and further subgroup analysis strengthened the outcome, with minor heterogeneity in non-Asian countries. In contrast, the early mortality was not significantly different between the PNH+ and PNH– groups (OR 0.54; 95% CI 0.26–1.10; p = 0.09). Conclusions: The meta-analysis suggested an evidence-based role for PNH clones in predicting a better response in AA patients with immunosuppression.