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

Abstract

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 MRD<0.01% (MRD1-) and thirty-seven (64%) were MRD>0.01% (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; P<0.001) and PFS (progression-free survival, 52.3 months vs 11.9 months; P=0.006) than those of MRD>0.01%, 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.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

“…In larger studies, sequential monitoring of molecular markers after allo-HSCT is mandatory to determine the optimal timing for predicting relapse and for therapeutic intervention. 48,49 According to CMML epidemiological statistics, almost 90% of cases occur in patients older than 60 years. 4,35,50 We reviewed the literatures on the age of CMML patients in Western (Germany, 29,30,51 France, 13,19,52 America, 8,11,12,15,17,20,25,26,28,40,53,54 Italy, 39,55 Greece, 14 and Denmark, 24 ) and Eastern countries (Japan With the development and advancement of nonmyeloablative and reduced-intensity allogeneic stem cell transplantation, significant progress has been made over the past decade in allo-HSCT for elderly patients.…”

“…Taking into account the methodical restrictions of this retrospective analysis, the confirmation of this conclusion in a well‐designed prospective trial is needed. In larger studies, sequential monitoring of molecular markers after allo‐HSCT is mandatory to determine the optimal timing for predicting relapse and for therapeutic intervention 48,49 …”

“…According to CMML epidemiological statistics, almost 90% of cases occur in patients older than 60 years 4,35,50 . We reviewed the literatures on the age of CMML patients in Western (Germany, 29,30,51 France, 13,19,52 America, 8,11,12,15,17,20,25,26,28,40,53,54 Italy, 39,55 Greece, 14 and Denmark, 24 ) and Eastern countries (Japan 16,22,27 and China, 6,43,49,56–63 ), and the results showed that the median age of CMML patients in Eastern countries was younger (38–70 years vs. 44–73 years), and the median age of CMML patients undergoing allo‐HSCT was similar in Eastern and Western countries (38–63 years vs. 44–64 years). However, the age of CMML patients undergoing allo‐HSCT was lower in both Eastern and Western countries.…”