Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes

Abstract

The impact of disease burden on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (SCT) has not been well defined. Data from several retrospective series suggest that overt leukemia at the time of transplant increases the risk of relapse. We reviewed the outcomes of 68 consecutive adults with AML (n=60) or myelodysplastic syndromes (MDS) (n=8) who received an allogeneic SCT at the University of Chicago between May 1986 and October 2002 to confirm the importance of currently recognized risk factors for overall survival (OS) and progression-free survival (PFS). In addition, we wanted to determine whether quantification of residual disease by blast percentage or cytogenetic abnormalities at the time of SCT was correlated with outcome. AML subtypes based on the FAB classification were as follows: M0=9, M1=9, M2=16, M3=2, M4=16, M5=3, M6=5. Cytogenetic analysis was available from 52 patients. Using standard morphologic criteria, 34 patients were in complete remission (CR) and 34 had visible leukemia present. The majority of donors were HLA-identical siblings (n=55). In all, 56 patients received myeloablative conditioning regimens and 12 received a reduced-intensity, fludarabine-based conditioning regimen. OS and PFS times were 7.1 months (95% CI, 4.8-10.4) and 5.1 months (95% CI, 3.2-7.8), respectively. Median follow-up from SCT was 4.6 years (range, 0.6-17.0) for survivors. In multivariate analysis, the following factors were found to be associated with worse survival: (1) increased percentage of blasts in the bone marrow at the time of SCT, (2) presence of acute graft-versus-host disease, (3) mismatched donor, (4) Zubrod performance score of >/=2, and (5) age >/=45 years. We also found a trend towards improved outcome among patients in cytogenetic remission as compared to those who had residual cytogenetic abnormalities and those in overt relapse. These data support an association between pre-transplant disease burden and poor outcome after SCT.