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

Walter RB, Gyurkocza B, Storer BE, Godwin CD, Pagel JM, Buckley SA, Sorror ML, Wood BL, Storb R, Appelbaum FR, Sandmaier BM - Leukemia (2014)

Bottom Line: 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.These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning.

View Article: PubMed Central - PubMed

Affiliation: 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA [3] Department of Epidemiology, University of Washington, Seattle, WA, USA.

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.

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Association between pre-HCT MRD, as determined by multiparameter flow cytometry, and outcome for AML patients following nonmyeloablative (NMA) or myeloablative (MA) HCTEstimates 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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Figure 2: Association between pre-HCT MRD, as determined by multiparameter flow cytometry, and outcome for AML patients following nonmyeloablative (NMA) or myeloablative (MA) HCTEstimates 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.

Mentions: There were a total of 101 deaths, 78 relapses, and 39 NRM events contributing to the probability estimates for OS, DFS, relapse, and NRM stratified by MRD status for NMA and MA patients. The median follow-up after HCT among survivors was 50.6 (13.7–85.3) months for NMA patients and 38.8 (12.2–84.8) months for MA patients, respectively. As summarized in Table 2, among NMA patients, the 3-year estimates of OS were 48% and 41% for MRDneg and MRDpos patients, respectively; among MA patients, 3-year OS was estimated to be 76% and 25%, respectively (Figure 2A). For DFS, similar estimates were 42% and 33% for MRDneg and MRDpos NMA patients and 71% and 13% for MRDneg and MRDpos MA patients (Figure 2B). Three-year estimates of relapse for NMA patients were 28% and 57%, respectively, and 22% and 63%, respectively, for those who received MA conditioning (Figure 2C). Finally, following NMA conditioning, the 3-year estimates of NRM where 30% and 10% for MRDneg and MRDpos patients, respectively, whereas similar estimates were 7% and 23% following MA conditioning (Figure 2D).


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

Walter RB, Gyurkocza B, Storer BE, Godwin CD, Pagel JM, Buckley SA, Sorror ML, Wood BL, Storb R, Appelbaum FR, Sandmaier BM - Leukemia (2014)

Association between pre-HCT MRD, as determined by multiparameter flow cytometry, and outcome for AML patients following nonmyeloablative (NMA) or myeloablative (MA) HCTEstimates 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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4254901&req=5

Figure 2: Association between pre-HCT MRD, as determined by multiparameter flow cytometry, and outcome for AML patients following nonmyeloablative (NMA) or myeloablative (MA) HCTEstimates 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.
Mentions: There were a total of 101 deaths, 78 relapses, and 39 NRM events contributing to the probability estimates for OS, DFS, relapse, and NRM stratified by MRD status for NMA and MA patients. The median follow-up after HCT among survivors was 50.6 (13.7–85.3) months for NMA patients and 38.8 (12.2–84.8) months for MA patients, respectively. As summarized in Table 2, among NMA patients, the 3-year estimates of OS were 48% and 41% for MRDneg and MRDpos patients, respectively; among MA patients, 3-year OS was estimated to be 76% and 25%, respectively (Figure 2A). For DFS, similar estimates were 42% and 33% for MRDneg and MRDpos NMA patients and 71% and 13% for MRDneg and MRDpos MA patients (Figure 2B). Three-year estimates of relapse for NMA patients were 28% and 57%, respectively, and 22% and 63%, respectively, for those who received MA conditioning (Figure 2C). Finally, following NMA conditioning, the 3-year estimates of NRM where 30% and 10% for MRDneg and MRDpos patients, respectively, whereas similar estimates were 7% and 23% following MA conditioning (Figure 2D).

Bottom Line: 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.These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning.

View Article: PubMed Central - PubMed

Affiliation: 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA [3] Department of Epidemiology, University of Washington, Seattle, WA, USA.

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.

Show MeSH
Related in: MedlinePlus