Prognostic implication of early minimal residual disease evaluation in patients with chronic myelomonocytic leukemia

To investigate the prognostic implication of minimal residual disease (MRD) evaluation in chronic myelomonocytic leukemia (CMML), we conducted a restropective study included a total of 174 CMML patients in our hospital from January 2010 to March 2021. In which 50/174 (29%) bone marrow samples were conducted by multiparameter flow cytometry (FCM) assessed MRD analysis after the first three cycles of treatment and were included in this study. MRD was detected by six- to eight-colour FCM. The achievement of early MRD negativity had better clinical outcomes in patients with CMML, which fared better prognosis in terms of not only PFS (P=0.006) but also OS (P=0.02) after the first cycle, and PFS (P=0.023 and P=0.041) after the second and third cycles, whereas no significantly influence in OS. In addition, MRD negative after initial treatment remained its independent prognostic value associated with PFS (adjusted hazard ratio [HR] 0.161, 95 CI 0.035-0.738; P=0.019) and OS (adjusted HR 0.136; 95 CI 0.017-1.077; P=0.059), indicating that patients with MRD-negative after the initial treatment alone could obtain the greatest clinical benefit. According to MRD level, the patients were divided into 4 different groups: very low risk (fewer than 10(-4) cells) in 15 cases, low risk (10(-4) to 10(-3) cells) in 6; and 6 were at intermediate risk (fewer than 10(-3) to 10(-2) cells). The rest of 23 patients were were assigned to the high-risk grades (more than 10(-2) residual cells), we find this risk stratification model is significantly associated with better PFS (P=0.002) but marginal significantly associated with OS (P=0.068). Notably, patients with DNMT3A mutation fared a shorter PFS in the MRD positive subgroup (P=0.068). MRD is highly predictive of prognosis, and its combination with molecular profile 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.

Automated summary

In patients with chronic myelomonocytic leukemia (CMML), minimal residual disease (MRD) evaluation has significant prognostic implications. Early MRD negativity after treatment is associated with better clinical outcomes. MRD negativity after initial treatment remains an independent prognostic factor. Risk stratification based on MRD levels can predict patient outcomes.