Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission?

Abstract

Purpose: Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution.

Patients and methods: We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive.

Results: Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups.

Conclusion: The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments.

Fig 1.

Cumulative incidences of acute graft-versus-host disease (GVHD) and chronic GVHD stratified by disease status. Estimates of (A) grade 3 or 4 acute GVHD and (B) chronic GVHD after myeloablative allogeneic hematopoietic cell transplantation (HCT) for adults with acute myeloid leukemia (AML), shown individually for patients in minimal residual disease (MRD) –negative (n = 235) and MRD-positive (n = 76) morphologic remission as well as those with active AML (n = 48).

Fig 2.

Association between pretransplant disease status and outcome for patients with acute myeloid leukemia (AML) after myeloablative hematopoietic cell transplantation (HCT). Estimates of (A) overall survival, (B) progression-free survival, (C) cumulative incidence of relapse, and (D) cumulative incidence of nonrelapse mortality (NRM) after myeloablative allogeneic HCT for adults with AML, shown individually for patients in minimal residual disease (MRD) –negative (n = 235) and MRD-positive (n = 76) morphologic remission as well as those with active AML (n = 48).

Fig A1.

Association between pretransplant disease status and outcome for patients with acute myeloid leukemia (AML) undergoing myeloablative hematopoietic cell transplantation (HCT) while in morphologic remission. Estimates of (A) overall survival and (B) progression-free survival after myeloablative allogeneic HCT for adults with AML, shown individually for patients in minimal residual disease (MRD)–negative remission 1 (n = 181), MRD-negative remission 2 (n = 54), MRD-positive remission 1 (n = 51), and MRD-positive remission 2 (n = 25). neg, negative; pos, positive.

Fig A2.

Association between pretransplant treatment history and outcome for patients with acute myeloid leukemia (AML) undergoing myeloablative hematopoietic cell transplantation (HCT) while having active disease. Estimate of overall survival after myeloablative allogeneic HCT for adults with AML, shown individually for patients with untreated newly diagnosed (ND) disease (n = 7), patients with relapsed AML who did not undergo pre-HCT salvage chemotherapy (n = 16), and patients who experienced failure of salvage chemotherapy for either relapsed or refractory (RR) AML (n = 25).