Pb2046: changings in genetic definition and management of acquired aplastic anemia: a single center experience

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Acquired aplastic anemia (AA) is an autoimmune disorder characterized by pancytopenia and hypoplastic bone marrow, with risk of transformation to myeloid neoplasms. In the last years, a better definition of genetic lesions, through next generation sequencing (NGS) and single-nucleotide polymorphism array (SNP-A) karyotyping and the progress in treatment strategies are changing the management of these syndromes. Aims: We studied the improvement in genetic definition and the changings in therapeutic management of AA in the last 10 years. Methods: We conducted a single center retrospective study, including patients with AA referred to our institute in the last 15 years. Data about clinical and hematologic features, management, evolution and outcomes were compared between patients with a diagnosis dated before or after 2013. Results: Overall, data about 541 AA patients were collected. AA diagnosis dated before 2013 in 334 patients and after that date in 207. Mean age at diagnosis was 44 (2-82) years. Disease severity at diagnosis, according to Camitta’s Criteria was similar between the two groups (37% non-severe, 41% severe and 22% very-severe), as well as hematologic parameters (Table 1). An overlap diagnosis between AA and hypoplastic myelodysplastic syndrome was done in 15% of patients. More than 80% in both groups required at least a therapy line, with 30% requiring >1 line and 12% >2, but with a higher n° of therapy lines and a major n° of anti-thymocyte globulin (ATG) courses in the historic group [1.5 (σ 0.8; range 1-4) vs 1.7 (σ 1.1; range 1-8) therapy lines, p 0.02 and 1 (σ 0.2; range 1-2) vs 1.3 (σ 0.6; range 1-5) ATG-courses, p <0.001]. In the modern group, ATG was less used both in 1st and 2nd line comparing with the historic one (51 vs 64%, p 0.009 and 22 vs 55%, p <0.001) with a larger use of eltrombopag. Allogenic transplant was performed in 27% of patients overall, with a shorter time from diagnosis in the modern group [1.5 (σ 1.9; range 0.1-8.7) vs 4.4 (σ 6.2; range 0.2-25.5) years, p 0.002]. Karyotype at diagnosis was available in 66% of patients (49% of historic patients and 93% of moderns). In 70 modern patients a SNP-A was done at diagnosis and for 25 both conventional and SNP-A karyotyping were available. In 4 (16%), SNP-A revealed a karyotype abnormality not detected by the conventional cytogenetics and in 9 (36%) permitted to bypass a failed conventional karyotyping. Overall, abnormal karyotype was detected in 10% and 23% of patients at diagnosis and at last follow-up, respectively (p <0.001) while mutations in the myeloid NGS panel was present in 12% at diagnosis and 31% at last follow-up (p<0.001). A paroxysmal nocturnal hemoglobinuria (PNH) clone was detected in more than 50% of patients with an increase in clone size overtime (18.2% (0.02-99.9) vs 24.1% (0.02-100), p 0.03) and development of hemolytic PNH in 10% of cases. Evolution to myelodysplastic syndrome or acute myeloid leukemia occurred in 11 and 1.5% of cases with higher rate in the historic cohort, probably due to the longer follow-up. Mortality rate was 24%, with AA-related complications as the most frequent cause of death. Summary/Conclusion: A better definition of cytogenetic and molecular features of AA, as well as the advent of eltrombopag and the improvement of transplant accessibility and outcomes, are changing the management and the treatment landscape of AA patients.Keywords: Aplastic anemia, Bone marrow failure