Abstract
Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated. To investigate PRT choices based on dynamic MRD in patients with IR-AML. This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020. Receipt of chemotherapy, auto-SCT, or allo-SCT. The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival. Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90]; P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58]; P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78]; P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24]; P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64]; P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46]; P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64]; P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59]; P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98]; P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94]; P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68]; P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42]; P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08]; P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33]; P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35]; P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55]; P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53]; P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73]; P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94]; P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33]; P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56]; P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75]; P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81]; P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76]; P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70]; P = .007). This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.
Highlights
Most younger patients with acute myeloid leukemia (AML) can achieve complete remission (CR) with induction chemotherapy.1 After CR, further postremission treatment (PRT) would be necessary to prevent relapse.2 Postremission treatment usually consists of either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy
Among participants with Measurable residual disease (MRD) after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse, better leukemia-free survival, and overall survival vs chemotherapy
Meaning This study suggests that clinical decisions based on dynamic measurable residual disease might be associated with improved therapy stratification and optimized postremission treatment for patients with intermediate-risk acute myeloid leukemia
Summary
Most younger patients with acute myeloid leukemia (AML) can achieve complete remission (CR) with induction chemotherapy. After CR, further postremission treatment (PRT) would be necessary to prevent relapse. Postremission treatment usually consists of either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy. Autologous SCT (auto-SCT) and chemotherapy carry a lower risk of transplant-related mortality compared with allo-SCT.. Some studies have suggested that a survival benefit is associated with the use of allo-SCT in patients with IR-AML, whereas other studies have showed that auto-SCT or chemotherapy had no significant survival differences compared with allo-SCT.. Some studies have suggested that a survival benefit is associated with the use of allo-SCT in patients with IR-AML, whereas other studies have showed that auto-SCT or chemotherapy had no significant survival differences compared with allo-SCT.4,12,13 These studies highlight the need to find additional factors associated with survival outcomes that optimize PRT choices for patients with IR-AML Allogeneic SCT (allo-SCT) is generally accepted as the most effective PRT to prevent relapse, but it has relatively high rates of transplant-related mortality. Autologous SCT (auto-SCT) and chemotherapy carry a lower risk of transplant-related mortality compared with allo-SCT. this lower risk of transplant-related mortality is offset by a higher risk of relapse owing to the lack of a graft-vs-leukemia effect and the potential infusion of leukemia cells in grafts. Currently, decisions for PRT depend mainly on risk stratification based on cytogenetics and molecular markers, but it remains controversial, for patients with intermediate-risk AML (IR-AML). For instance, some studies have suggested that a survival benefit is associated with the use of allo-SCT in patients with IR-AML, whereas other studies have showed that auto-SCT or chemotherapy had no significant survival differences compared with allo-SCT. these studies highlight the need to find additional factors associated with survival outcomes that optimize PRT choices for patients with IR-AML
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