Monitoring for Minimal Residual Disease before and after Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed Acute Leukemia

Objective:To assess the relevance between minimal residual disease (MRD) levels and disease recurrence and prognosis in patients with acute leukemia before and after hematopoietic stem cell transplantation (HSCT), and further to explore potential benefit based on pre-transplant MRD stratification.

Methods: A total of 113 patients with newly diagnosed acute leukemia in Fujian Union hospital from April 2013 to April 2019 were retrospectively analyzed. 94 patients were complete remission (CR)( 50 cases of AML and 44 cases of ALL). 19 patients didn't achieve CR( 10 patients with AML and 9 patients with ALL). The median age was 26(1-56) years. 67 patients were male and 46 patients were female. The sources of hematopoietic stem cell include bone marrow, cord blood and peripheral blood stem cell. All patients underwent myeloablative conditioning before transplantation. Standard graft-versus-host disease (GVHD) prophylaxis was applied in all patients. MRD was measured by flow cytometry and real-time quantitative polymerase chain reaction(PCR). MRD values >10^-4 or BCR-ABL were considered positive for minimal residual disease and compared with bone marrow morphological findings. Median follow time was 15.2 (2.2 to 70.5) months.

Results: Among patients in CR, achieving pre-MRD negativity was associated with longer 2-year relapse-free survival (2-year RFS; 81.4% vs 49.1%; P=0.003) and 2-year overall survival (2-year OS; 84% vs 50.6%; P=0.012). Compared to pre-MRD^neg patients, pre-MRD^pos patients had a higher incidence of relapse (31.2% vs. 5.1%, P=0.001). There was no significant difference between OS and MRD level after transplantation (OS; post-MRD^neg 82.9% vs. post-MRD^pos 66.7%, P =0.468). In the second set of analyses, CR patients were classified into the MRD^pos /MRD^pos group, the MRD^pos /MRD^neg group, the MRD^neg /MRD^pos group, and the MRD^neg /MRD^neg group according to MRD dynamics. Compared to the other three groups, patients from the MRD^pos /MRD^pos group had higher cumulative incidences of relapse (MRD^pos /MRD^pos, 48.3%; MRD^pos /MRD^neg, 22.2%, MRD^neg /MRD^pos,40.0%; MRD^neg /MRD^neg, 2.7%; P<0.000) and worse 2-year RFS(MRD^pos /MRD^pos, 34.3%; MRD^pos /MRD^neg, 60.0%, MRD^neg /MRD^pos,60.0%; MRD^neg /MRD^neg, 76.6%; P=0.012). 1-year RFS and 1-year OS were similar in patients who didn't achieve CR, regardless of the post-MRD response(1-year RFS; 50.0% vs. 14.3%, P=0.063 and 1-year OS; 50.0% vs. 14.3%, P=0.184).In this group, 7 patients with MRD-positive after transplantation did not survive, but 12 post-HSCT MRD-negative patients had not relapsed.

Conclusion: MRD can be used as a sensitive indicator to evaluate disease prognosis. Patients who are in morphologic remission and have no evidence of MRD before the HSCT come to encouraging leukemia-free survival. Continuous regular dynamic observation is important for guiding disease recurrence and prognosis.