Background and methods Occasionally, patients with acquired aplastic anemia (AA) present with abnormal cytogenetics in bone marrow cells at diagnosis. The diagnosis and treatment of such patients have not been established and have been center-dependent. We have treated adult AA patients with abnormal cytogenetics in a same way as those with normal cytogenetics. Presently, the characteristics and clinical outcomes of 600 adult AA patients who had successful cytogenetics at diagnosis were retrospectively evaluated. Our aim was to determine the characteristics and clinical courses of AA patients with cytogenetic abnormalities at diagnosis who were treated as those with normal cytogenetics.

ResultsCharacteristics: Of the evaluable patients, 572 (95.3 %) had normal cytogenetics and 28 (4.7 %) had abnormal cytogenetics at diagnosis. The most frequent abnormality was trisomy 8 (n=15) followed by monosomy 7/deletion 7q (n=5) and deletion 1q (n=5). Other chromosome abnormalities were isochromosome 17q (n=1), trisomy 15 (n=1) and monosomy 21 (n=1). There was no significant statistical difference in gender (P=0.562), Hepatitis B or C infection (P=0.402), paroxysmal nocturnal hemoglobinuria (P=0.709) and severity of AA (P=0.325) between patients displaying normal cytogenetics and abnormal cytogenetics. The age of abnormal cytogenetics patients was significantly lower than normal cytogenetics patients (P<0.001).

Immunosuppressive therapy: A total of 334 patients received immunosuppressive therapy using antithymocyte globulin and cyclosporine. Six months after commencement of therapy, 165 (50.9 %) patients responded partially or completely. Multivariate analysis revealed abnormal cytogenetics (HR=0.250; 95% CI=0.077–0.808; P=0.021), absence of paroxysmal nocturnal hemoglobinuria and age (≥ 67) as independent predictors for the poor response to immunosuppressive therapy.

Leukemic transformation: Kaplan-Meier modeling revealed that abnormal cytogenetics was also associated with higher cumulative leukemic transformation rate (P<0.001) and lower leukemia-free survival (P=0.021). Of note, the cause of all deaths in non-severe AA patients with abnormal cytogenetics was leukemic transformation.

Conclusion: Patients with abnormal cytogenetics at diagnosis of AA tend to respond poorly to immunosuppressive therapy and present with a high leukemic transformation risk, which suggests that cytogenetic abnormalities should be emphasized more than morphological features in diagnosis and treatment decision in AA.

Disclosures: No relevant conflicts of interest to declare.

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