Open AccessPS1040 DETECTION OF MRD MAY PREDICT THE OUTCOME OF PATIENTS WITH ACUTE MYELOID LEUKEMIA WITH BIALLELIC CEBPA MUTATIONS
Author(s) -
Wang J.,
Lu R.Q.,
Zhao X.S.,
Huang X.J.,
Ruan G.R.,
Jiang H.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000562456.04617.19
Subject(s) - indel , cebpa , biology , computational biology , gene , genetics , dna sequencing , mutation , exome , genome , exome sequencing , genotype , single nucleotide polymorphism
Background: Acute myeloid leukemia (AML) patients with biallelic CEBPA mutations have a 30–50% relapse rate after standard chemotherapy. Aims: This study established the value of multiparameter flow cytometric minimal residual disease (MFC‐MRD) detection and compares the outcomes of allogeneic stem cell transplantation (allo‐HSCT) versus chemotherapy in adult biallelic CEBPA AML patients after relapse. Methods: From March 2014 to September 2018, 120 patients with newly diagnosed acute myeloid leukemia with biallelic CEBPA mutations were treated with chemotherapy. MRD was detected by MFC after each cycle of induction and consolidation chemotherapy and every 3 months later. Results: Median age was 38 (16–69) years. One hundred (100%) achieved complete remission (CR) including 110 patients (91.7%) who achieved it with only 1 induction course. The median follow‐up was 27.5 (3–62) months. The 3‐year Cumulative incidence of relapse (CIR), disease‐free survival (DFS) and overall survival (OS) were 35.7%, 62.2%, and 81.7% respectively. MRD turned to negative at the median follow‐up of 2 (1–7) months. MRD positive after 2 consolidation cycles was the adverse factor of CIR (73.6% vs. 25.9%, P < 0.001), DFS (26.4% vs. 71.2%, P < 0.001) and OS (58.5% vs. 88.7%, P = 0.002). MRD sustained positive status after 2 consolidation cycles and MRD negative status losed in 9 and 22 patients, were the adverse factors of CIR (100% vs. 28.2%, P < 0.001; 95.5% vs. 4.5%, P < 0.001; respectively) DFS (0 vs. 69.0%, P < 0.001; 4.5% vs. 91.6%, P < 0.001; respectively) and OS (33.3% vs. 88.2%, P < 0.001; 64.5% vs. 96%, P < 0.001; respectively), eventually 100% and 95.5% relapsed at the median follow‐up of 6 (3–15) and 11(3–26) months respectively. Multivariate analysis showed that MRD sustained positive status after 2 consolidation cycles and MRD negative status loses was the favorable factor of CIR, DFS and OS. (HR = 50.9, 95%CI: 15.1–167.8, P < 0.001; HR = 24.0, 95%CI: 9.8–58.8, P < 0.001; HR = 11.1, 95%CI: 3.2–39.1, P < 0.001; respectively). In totally 33 patients relapsed at the median follow‐up of 9 (3–26) months, 3 patients give up, 18 (60.0%) patients achieved CR2 after induction again. 15 CR2 and 4 non‐remission patients underwent allo‐HSCT achieved superior 3‐year OS (83.0% vs 5.1%; p = 0.034; 75.0% vs 0%; p = 0.006; respectively) than did consolidation chemotherapy. Summary/Conclusion: MRD sustained positive status after 2 consolidation cycles and MRD negative status loses could predict relapse, and allo‐HSCT is superior to chemotherapy after relapse.