Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission

Abstract

Minimal residual disease (MRD) before myeloablative hematopoietic cell transplantation (HCT) is associated with adverse outcome in acute myeloid leukemia (AML) in first complete remission (CR1). To compare this association with that for patients in second complete remission (CR2) and to examine the quantitative impact of MRD, we studied 253 consecutive patients receiving myeloablative HCT for AML in CR1 (n = 183) or CR2 (n = 70) who had pre-HCT marrow aspirates analyzed by 10-color flow cytometry. Three-year estimates of overall survival were 73% (64%-79%) and 32% (17%-48%) for MRDneg and MRDpos CR1 patients, respectively, and 73% (57%-83%) and 44% (21%-65%) for MRDneg and MRDpos CR2 patients, respectively. Similar estimates of relapse were 21% (14%-28%) and 58% (41%-72%) for MRDneg and MRDpos CR1 patients, respectively, and 19% (9%-31%) and 68% (41%-85%) for MRDneg and MRDpos CR2 patients, respectively. Among the MRDpos patients, there was no statistically significant evidence that increasing levels of MRD were associated with increasing risks of relapse and death. After multivariable adjustment, risks of death and relapse were 2.61 times and 4.90 times higher for MRD(pos) patients (P < .001). Together, our findings indicate that the negative impact of pre-HCT MRD is similar for AML in CR1 and CR2 with even minute levels (≤ 0.1%) as being associated with adverse outcome.

Figure 1

Association between pre-HCT MRD, as determined by multiparameter flow cytometry, and post-HCT outcome for AML patients in CR1 and CR2. Estimates of OS (A), DFS (B), cumulative incidence of relapse (C), and cumulative incidence of NRM (D) after myeloablative allogeneic HCT for AML in complete morphologic remission, shown individually for MRD^neg (n = 147; black solid line) and MRD^pos (n = 36; gray solid line) CR1 patients, as well as MRD^neg (n = 52; black dashed line) and MRD^pos (n = 18; gray dashed line) CR2 patients.

Figure 2

Relationship between pre-HCT MRD levels, as determined by multiparameter flow cytometry, and post-HCT outcome for AML patients in morphologic remission. Estimates of OS (A), DFS (B), cumulative incidence of relapse (C), and cumulative incidence of NRM (D) after myeloablative allogeneic HCT for AML in complete morphologic remission, shown individually for patients without flow cytometric evidence of MRD (MRD^neg; n = 199; black solid line), low-level MRD (≤0.1%; n = 14; gray solid line), intermediate-level MRD (>0.1%-1%; n = 24; gray long-dashed line), or high-level MRD (>1%; n = 16; gray short-dashed line).