Cytogenetic peripheral blood monitoring in azacitidine treated patients with high-risk MDS/sAML: A monocentric real-world experience. (January 2023)

• Record Type: Journal Article
• Authors: Braulke, Friederike; Schweighöfer, Adrian; Schanz, Julie; Shirneshan, Katayoon; Ganster, Christina; Pollock-Kopp, Beatrix; Leha, Andreas; Haase, Detlef
• Is Part Of: Leukemia research. Volume 124(2023)
• Publication Date: 2023-01
• Subjects: Cytogenetic monitoring -- Karyotype evolution -- High-risk MDS -- FISH -- Chromosome banding analyses -- Azacitidine -- Hypomethylating agents -- Cytogenetic response; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2022.106996
• Languages: English
• ISSNs: 0145-2126

Abstract

Abstract: In this single center retrospective analysis 76 patients with high-risk (HR) myelodysplastic syndrome (MDS) treated with azacitidine (AZA) were reviewed for response, especially cytogenetic response (cyR) using repeated chromosome banding analyses (CBA) of bone marrow (bm) metaphases and frequent sequential Fluorescence-in-situ Hybridization (FISH) analyses of immunomagnetically enriched CD34 + circulating peripheral blood cells (CD34 +pb-FISH). In total, 526 CD34 +pb-FISH analyses and 236 CBA were examined. Median observation time was 8.45 months, median number of AZA cycles applied was 8, median overall survival (OS) was 14.9 months, 42.1 % of patients responded to therapy according to IWG criteria: 5 complete response (CR), 0 partial response (PR), 12 bmCR, 15 stable disease with hematologic improvement (HI). HI was reached in 36.8 % of patients, 31.5 % became transfusion-independent. By CBA or CD34 +pb-FISH 20.4 % and 31.6 % of patients showed cyR, respectively. HI rate was significantly higher in cytogenetic responders than in non-responders, but there was no impact on OS or leukemia-free-survival. Cytogenetic responders showed significantly better OS than non-responders. Patients with ≥ 6 AZA cycles had significantly better OS than patients with < 6 cycles applied. Karyotype evolution (KE) as a manifestation of cytogenetic progression was diagnosed in 29.5 % and 17.1 % of patients by CBA and CD34 +pb-FISH, respectively. KE was associated with significantly poorer OS and leukemia-free-survival. Highlights: In a real-world setting 76 patients with high-risk MDS or secondary AML treated with azacitidine were retrospectively reviewed for especially cytogenetic response. the rate of hematologic improvement was significantly higher in cytogenetic responders than in non-responders, Cytogenetic responders showed significantly better overall survival than non-responders. Karyotype evolution (KE) as a manifestation of cytogenetic progression was associated with significantly poorer overall survival and leukemia-free-survival.