Prognostic Implication of Early Minimal Residual Disease Evaluation in Patients with Chronic Myelomonocytic Leukemia

Background: This article is performed to assess the significance of minimal residual disease (MRD) after one course of therapy in patients with chronic myelomonocytic leukemia (CMML). Methods: : From January 2010 to January 2022, a total of 158 patients who were newly diagnosed with CMML were enrolled, in which 58/158 (37%) patients were conducted by multiparameter flow cytometry (FCM) assessed MRD analysis after on cycle treatment and were included in this study. MRD was detected by six- to eight- colour FCM. Result: After one course of therapy, twenty-one (36%) patients achieved MRD0.01% (MRD1+). The patients in the MRD1+ group had lower platelet counts, higher 𝛽2-microglobulin, ferritin and BM1 myeloblasts (bone marrow myeloblasts after one cycle of therapy) than that of the MRD1- group (P=0.005, P=0.023, P=0.026 and P=0.007, respectively). Furthermore, a greater propotion of patients had JCK2 and SETBP1 mutation in MRD1- patients than in MRD1+ group (both P=0.037). At a median follow up time of 25.8 months (95%CI, 15.01-36.59), those patients who achieved MRD<0.01% after one course of therapy fared better prognosis in terms of both OS (overall survival, 54.9 months vs. 17.5 months; P0.01%, and 2-year OS rate (90% vs. 30%; P<0.001) and 2-year PFS rate (70% vs. 7%; P=0.004) were also higher. MRD1 status could determine the likelihood of progression after hematopoietic stem cell transplantation (HSCT), the 2-year PFS rate (100% vs. 24%, P=0.04) was higher in MRD1+ group than MRD1- group at the post-HSCT assessment. In addition, MRD1 status were independent prognostic factor of both PFS (HR, 3.326 [95%CI, 1.340-8.259]; P=0.01) and OS (HR, 4.614 [95%CI, 1.266-16.812]; P=0.02). Conclusion: MRD is highly predictive of prognosis, and it may help identify patients at increased risk for progression to further improve the management of patients with CMML. Large-scaled investigations are warranted to validate our conclusions and its potential in clinical practice.