Contributions
Abstract: S125
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 11:45 - 12:00
Location: Room A6
Background
The current definition of complete remission (CR) in patients with acute myeloid leukemia (AML) is based on recovery of normal blood counts after treatment and morphological assessment of the marrow. However, patients in CR can still harbor significant number of leukemic cells that may result in relapse. Minimal residual disease (MRD) assessment can establish, by different methods, the presence of 1:103- 1:106 leukemia cells. The level of MRD as assessed at particular time-points during AML treatment, and in particular prior to stem-cell transplantation (SCT), is an independent and important predictor of outcome. However, most of the existing data are available for CR1 and there is only limited data on the role of MRD in patients achieving CR2 following leukemic relapse.
Aims
To assess the impact of MRD status on transplantation outcomes in patients in CR2 at the time SCT.
Methods
We retrospectively analyzed SCT outcomes in a group of 1042 patients with de-novo AML in CR2 given SCT between 2006 and 2016 from HLA- matched siblings (n=719) or 10/10 matched unrelated donors (n=293), who had available MRD status data at the time of SCT and were registered in the data base of the ALWP of the EBMT. MRD methodology and allocation to MRD negative or MRD positive groups were determined by the individual participating centers and utilized molecular and/or immunophenotyping criteria.
Results
The median age was 49 years (range, 18-73), 558 males and 484 females. The conditioning regimen was myeloablative (n=610) or reduced-intensity (n=432) and 566 patients (54%) had in-vivo T-cell depletion. In all, 749 patients (72%) were MRD negative and 293 (28%) had positive MRD at the time of SCT. The only difference in patient characteristics between the MRD (-) and MRD (+) groups was a longer time from diagnosis to SCT in the MRD (-) group, 18 Vs. 16 months, respectively (P<0.001). In particular, there was no difference in the cytogenetic or molecular characteristics between the groups. The 2-year relapse rate was 24% (95%CI, 21-28) and 40% (95%CI, 34-46) in the MRD (-) and MRD (+) groups, respectively (P<0.001). The predicting factors for relapse in multivariate analysis were MRD (-) status (HR 0.57, P<0.001), good cytogenetics (HR 0.62, P=0.001), longer time from diagnosis to SCT (HR=0.97, P<0.001) and in-vivo T-cell depletion (HR 1.35, P=0.03). The 2-year LFS was 57% (53-61) and 46% (40-52%), respectively (P=0.001). The predicting factors for LFS were MRD (-) status (HR 0.76, P=0.01), good cytogenetics (HR 0.79, P=0.04) and longer time from diagnosis to SCT (HR=0.99, P<0.001). Age, gender, donor or conditioning type did not predict relapse or LFS rates.
Conclusion
Achieving a negative MRD status after second-line treatment for relapsed AML is associated with lower relapse rates and improved LFS after SCT. These observations are similar to the effect of MRD status in the frontline setting. MRD status pre SCT for AML relapsing patients achieving CR2 should dictate therapeutic strategies in this patient population.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Acute Myeloid Leukemia, Minimal residual disease (MRD), Stem cell transplant
Abstract: S125
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 11:45 - 12:00
Location: Room A6
Background
The current definition of complete remission (CR) in patients with acute myeloid leukemia (AML) is based on recovery of normal blood counts after treatment and morphological assessment of the marrow. However, patients in CR can still harbor significant number of leukemic cells that may result in relapse. Minimal residual disease (MRD) assessment can establish, by different methods, the presence of 1:103- 1:106 leukemia cells. The level of MRD as assessed at particular time-points during AML treatment, and in particular prior to stem-cell transplantation (SCT), is an independent and important predictor of outcome. However, most of the existing data are available for CR1 and there is only limited data on the role of MRD in patients achieving CR2 following leukemic relapse.
Aims
To assess the impact of MRD status on transplantation outcomes in patients in CR2 at the time SCT.
Methods
We retrospectively analyzed SCT outcomes in a group of 1042 patients with de-novo AML in CR2 given SCT between 2006 and 2016 from HLA- matched siblings (n=719) or 10/10 matched unrelated donors (n=293), who had available MRD status data at the time of SCT and were registered in the data base of the ALWP of the EBMT. MRD methodology and allocation to MRD negative or MRD positive groups were determined by the individual participating centers and utilized molecular and/or immunophenotyping criteria.
Results
The median age was 49 years (range, 18-73), 558 males and 484 females. The conditioning regimen was myeloablative (n=610) or reduced-intensity (n=432) and 566 patients (54%) had in-vivo T-cell depletion. In all, 749 patients (72%) were MRD negative and 293 (28%) had positive MRD at the time of SCT. The only difference in patient characteristics between the MRD (-) and MRD (+) groups was a longer time from diagnosis to SCT in the MRD (-) group, 18 Vs. 16 months, respectively (P<0.001). In particular, there was no difference in the cytogenetic or molecular characteristics between the groups. The 2-year relapse rate was 24% (95%CI, 21-28) and 40% (95%CI, 34-46) in the MRD (-) and MRD (+) groups, respectively (P<0.001). The predicting factors for relapse in multivariate analysis were MRD (-) status (HR 0.57, P<0.001), good cytogenetics (HR 0.62, P=0.001), longer time from diagnosis to SCT (HR=0.97, P<0.001) and in-vivo T-cell depletion (HR 1.35, P=0.03). The 2-year LFS was 57% (53-61) and 46% (40-52%), respectively (P=0.001). The predicting factors for LFS were MRD (-) status (HR 0.76, P=0.01), good cytogenetics (HR 0.79, P=0.04) and longer time from diagnosis to SCT (HR=0.99, P<0.001). Age, gender, donor or conditioning type did not predict relapse or LFS rates.
Conclusion
Achieving a negative MRD status after second-line treatment for relapsed AML is associated with lower relapse rates and improved LFS after SCT. These observations are similar to the effect of MRD status in the frontline setting. MRD status pre SCT for AML relapsing patients achieving CR2 should dictate therapeutic strategies in this patient population.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Acute Myeloid Leukemia, Minimal residual disease (MRD), Stem cell transplant