Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation

R B Walter, B Gyurkocza, B E Storer, C D Godwin, J M Pagel, S A Buckley, M L Sorror, B L Wood, R Storb, F R Appelbaum, B M Sandmaier, R B Walter, B Gyurkocza, B E Storer, C D Godwin, J M Pagel, S A Buckley, M L Sorror, B L Wood, R Storb, F R Appelbaum, B M Sandmaier

Abstract

Minimal residual disease (MRD) is associated with adverse outcome in acute myeloid leukemia (AML) after myeloablative (MA) hematopoietic cell transplantation (HCT). We compared this association with that seen after nonmyeloablative (NMA) conditioning in 241 adults receiving NMA (n=86) or MA (n=155) HCT for AML in first remission with pre-HCT bone marrow aspirates assessed by flow cytometry. NMA patients were older and had more comorbidities and secondary leukemias. Three-year relapse estimates were 28% and 57% for MRD(neg) and MRD(pos) NMA patients, and 22% and 63% for MA patients. Three-year overall survival (OS) estimates were 48% and 41% for MRD(neg) and MRD(pos) NMA patients and 76% and 25% for MA patients. This similar OS after NMA conditioning was largely accounted for by higher non-relapse mortality (NRM) in MRD(neg) (30%) compared with MRD(pos) (10%) patients, whereas the reverse was found for MRD(neg) (7%) and MRD(pos) (23%) MA patients. A statistically significant difference between MA and NMA patients in the association of MRD with OS (P<0.001) and NRM (P=0.002) but not relapse (P=0.17) was confirmed. After adjustment, the risk of relapse was 4.51 times (P<0.001) higher for MRD(pos) patients. These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no competing financial interests.

Figures

Figure 1. Cumulative incidences of acute GVHD…
Figure 1. Cumulative incidences of acute GVHD and chronic GVHD stratified by conditioning type and MRD status
Estimates of (A) grade 3 or 4 acute GVHD and (B) chronic extensive GVHD following myeloablative allogeneic HCT for AML in complete first morphologic remission, shown individually for MRDneg (n=65) and MRDpos (n=21) NMA patients as well as MRDneg (n=125) and MRDpos (n=30) MA patients, respectively.
Figure 2. Association between pre-HCT MRD, as…
Figure 2. Association between pre-HCT MRD, as determined by multiparameter flow cytometry, and outcome for AML patients following nonmyeloablative (NMA) or myeloablative (MA) HCT
Estimates of (A) overall survival, (B) disease-free survival, (C) cumulative incidence of relapse, and (D) cumulative incidence of non-relapse mortality following myeloablative allogeneic HCT for AML in complete first morphologic remission, shown individually for MRDneg (n=65) and MRDpos (n=21) NMA patients as well as MRDneg (n=125) and MRDpos (n=30) MA patients, respectively.

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