52 Impact of Pre-Transplant Minimal Residual Disease in Patients with AML Undergoing Myeloablative Cord Blood Transplantation

Track: BMT Tandem "Scientific" Meeting
Saturday, February 14, 2015, 4:45 PM-6:45 PM
Seaport Ballroom DE (Manchester Grand Hyatt)
Filippo Milano, MD, PhD , Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Brent L. Wood, MD , Laboratory Medicine & Pathology, University of Washington, Seattle, WA
Colleen Delaney, MD, MSc , Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Background: Pre-transplant minimal residual disease (MRD) is associated with inferior outcomes in patients with acute myeloid leukemia (AML) undergoing myeloablative hematopoietic cell transplantation (HCT) from related and unrelated donors1. However data on the impact of pre-transplant MRD after cord blood transplantation (CBT) are limited. Using prospectively collected data, we reviewed 80 consecutive patients with AML who received a myeloablative CBT between 2006 and 2013. Methods: The myeloablative preparative regimen consisted of TBI (1320 cGy), Cytoxan and Fludarabine (FLU) (n=50; 62%) or Treosulfan (Treo), FLU and 200 cGY TBI (n=30; 38%). Graft-versus-host-disease prophylaxis consisted of cyclosporine and mycophenolate mofetil. Ten-color multiparameter flow cytometry studies on bone marrow aspirates were performed before HCT to determine the presence of MRD. Any level of residual disease was considered MRD-positive (MRDpos). Results: Pre-transplant MRD was identified in 20 (25%) patients. The majority of patients (n=67; 84%) received a double-CB graft; the rest received a single-CB graft. Pre-transplant demographic and clinical characteristics were similar between the 2 groups (Table 1). Disease free survival (DFS) at 5 years was 69% (95% CI: 55-79) and 52% (95% CI: 29-72) for MRDneg and MRDpos patients, respectively (p=0.08) (Figure1A). Figure 1B and 1C show DFS by MRD for patients receiving different conditioning regimen. After adjusting for age, disease risk (low/intermediate vs. high/very high), and CR status (CR1 vs. ≥CR2), the relative hazard of overall mortality (OM) in the MRDpos group compared to the MRDneg group was suggestively different with a HR=2.36 (95%CI: 1.02-5.43; p=0.04). However, the impact of MRD on OM was only significant in patients receiving a Treo based regimen [(HR=9.5; 95% CI 1.84-49.5) p=0.007)] while no difference were seen in patients receiving high-dose TBI [(HR=1.28; 95% CI 0.44-3.74) p=0.64)]. Cumulative incidence of relapse was significantly higher in MRDpos patients, 31% (95%CI: 13-52) vs. 10% (95%CI: 4-20) in MRDneg (p=0.01) for the group as a whole. An higher proportion of relapses were observed in MRDpos  patients receiving Treo [34% vs. 8% (p=0.03)] while no differences were observed in patients receiving high-dose TBI [29% vs. 12% (p=0.10)]. Incidence of non-relapse mortality was 15% (95% CI: 4-34) and 19% (95%CI: 10-31) for MRDpos and MRDneg patients, respectively (p=0.81). Conclusion: Herein we demonstrate that the presence of pre-transplant MRD after myeloablative CBT is associated overall with adverse outcomes.  However, the presence of pre-transplant MRD impacted outcomes less if the patient received a high-dose TBI-based preparative regimen. Our study suggests furthering extending the use of CBT with high-dose TBI in AML MRDpos patients.

Disclosures:
C. Delaney, Biolife Solutions, advisor : Advisory Board
Novartis , advisor: chair, data safety monitoring board