P771: PROGNOSTIC CHARACTERISTICS OF PATIENTS WITH MDS WITH ABERRATIONS OF CHROMOSOME 5. DATA FROM THE DÜSSELDORF MDS REGISTRY

Abstract

Background: Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with a wide spectrum of biological and clinical features. Up to 20% of MDS patients present with aberrations of chromosome 5, either as isolated del(5q) or combined with other aberrations. Patients with a medullary blast count < 5% and isolated del(5q), or with one additional aberration except anomalies of chromosome 7, are diagnosed as MDS del(5q), a defined entity according to the WHO 2016 classification. They have a favorable prognosis compared to other types of MDS, although profound anemia, chronic transfusion dependency and the risk of disease progression into AML present clinical challenges. Aims: We analyzed the prognostic impact of karyotype complexity in MDS del(5q). Methods: From the Düsseldorf MDS registry we retrieved 499 patients with MDS or CMML according to WHO 2016, who showed any kind of del(5q). Biological and clinical parameters such as karyotype, IPSS-R and type of treatment were evaluated. Survival and progression to AML was calculated using Kaplan-Meier-plots. Cox regression analysis was performed to identify disease-related prognostic factors. Patients were followed up until Dec 31th 2021. Results: 58% of the patients were female, median age was 67 years. Median medullary blast count was 4% (0-19%), and median survival in the entire group was 28 months. For assessing the natural course of disease, we screened for patients with non-intensive treatment only (best supportive care, lenalidomide, low-dose Ara-C, hydroxyurea). Separation by medullary blast count (< 5%, 5-9% or ≥ 10%) was associated with significantly different median survival times, ranging from 63 months in the first group to 3 months in patients with ≥ 10% medullary blasts (p < 0.001). Survival was also affected by the cytogenetic risk group according to IPSS-R. Patients in the low-risk group (median survival 72 months) differed significantly from patients in the very high risk group (median survival 5 months) (p < 0.001). A similar trend was observed according to karyotype complexity represented by number of aberrations apart from del(5q). Median survival of patients with an isolated del(5q) was 86 months, while patients with a complex karyotype (del(5q) and ≥3 additional aberrations) had a median survival of 5 months. Biological risk factors were assessed using Cox regression analyses. Considering overall survival as endpoint, medullary blast percentage, cytogenetic risk group, and complexity of the karyotype had a significant impact on survival (p < 0.001). In the entire patient cohort, as well as among patients receiving non-intensive treatment, the rate of AML progression was significantly influenced by karyotype complexity (p < 0.001). While the median time to AML progression in both isolated del(5q) and del(5q) combined with one aberration had not been reached at the end of the observation period, the median time to AML progression for patients with del(5q) as part of a complex karyotype was 31 months in the entire cohort and 14 months in the low-intensity treatment group. Image:Summary/Conclusion: Both the IPSS-R cytogenetic risk group and the complexity of the 5q- karyotype showed prognostic impact in patients with del(5q). This was true for overall survival as well as risk of AML progression. Regardless of therapy or medullary blast count in patients with del(5q), the risk of AML progression increased dramatically with increasing complexity of the 5q- karyotype.