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

Roland B. Walter, Sarah A. Buckley, John M. Pagel, Brent L. Wood, Barry E. Storer, Brenda M. Sandmaier, Min Fang, Boglarka Gyurkocza, Colleen Delaney, Jerald P. Radich, Elihu H. Estey and Frederick R. Appelbaum

Key points

  • The negative impact of pre-HCT flow cytometrically-determined minimal residual disease (MRD) is similar for AML in CR1 and CR2

  • Even minute levels of MRD (≤0.1%) are associated with adverse outcome

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 CR (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, and 73% (57-83%) and 44% (21-65%) for MRDneg and MRDpos CR2 patients. Similar estimates of relapse were 21% (14-28%) and 58% (41-72%) for MRDneg and MRDpos CR1 patients and 19% (9-31%) and 68% (41-85%) for MRDneg and MRDpos CR2 patients. 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 MRDpos patients (P<0.001). 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%) being associated with adverse outcome.

  • Submitted June 3, 2013.
  • Accepted July 6, 2013.