Deciphering treatment patterns in non-severe/moderate aplastic anemia: an international observational study

Abstract

Non-severe aplastic anemia is a rare bone marrow failure disorder characterized by variable degrees and combination of cytopenias, with limited data on management and outcome. We describe a large multicentric series of 259 patients, focusing on clinical and molecular features, treatment, evolution, and survival. The majority required treatment with cyclosporine (CyA) alone (N = 84) or in combination with anti-thymocyte globulin (ATG,44) or eltrombopag (20), eltrombopag alone (10), or others (25) including androgens. Similar outcomes were observed across different strategies, with a 6-month overall response rate of 73% for CyA, 74% for ATG plus CyA, 68% for CyA plus eltrombopag, 87% for eltrombopag, and 79% for others. Notably, 56 patients (39%), mainly receiving CyA plus eltrombopag, achieved a trilineage response (p = 0.02). Progression to myeloid neoplasms was limited (8%) and not related to mutational status. Hemolytic PNH developed in 10% of cases, being predicted by detection of small clones at diagnosis. Survival was negatively impacted by age, male gender, LDH, platelets/erythrocyte transfusion need, and somatic mutations by NGS, and positively by higher neutrophils at diagnosis, PNH clones, and trilineage response at 6 and 12 months. Multivariable analysis confirmed the detrimental role of age and the favorable association with PNH clone and trilineage response at 6 months.

Fig. 1. Clonal evolution in patients with non-severe aplastic anemia.

Cumulative incidence of evolution of non-severe aplastic anemia into myeloid neoplasm (dashed line) and of development of hemolytic paroxysmal nocturnal hemoglobinuria (PNH, continuous line).

Fig. 2. Overall survival in patients with non-severe aplastic anemia.

Overall survival in patients with non-severe aplastic anemia altogether (A) or divided by gender (B), need of transfusions (C, D), presence of paroxysmal nocturnal hemoglobinuria (PNH) clone (E), presence of mutations by next generation sequencing (NGS, F), and response to treatment (G). RBC red blood cell.