Comparison Of Minimal Residual Disease As Outcome Predictor For AML Patients In First Complete Remission Undergoing Myeloablative Or Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

Minimal residual disease (MRD) has been recognized as a strong, independent predictor of increased relapse risk and poor outcome for patients with acute myeloid leukemia (AML) in first complete remission (CR) undergoing myeloablative (MA) allogeneic hematopoietic cell transplantation (HCT). As the relationship between MRD and outcome is less studied for AML patients undergoing nonmyeloablative (NMA) HCT, we herein conducted a comparative analysis to assess this association relative to that seen in MA HCT.

We studied 272 consecutive patients receiving NMA (n=63) or MA (n=209) HCT for AML in first CR or CR with incomplete blood count recovery (CRi) between May 2006 and May 2012. Pre-HCT bone marrow aspirates were obtained in all patients and analyzed by routine karyotyping and ten-color flow cytometry. MRD was identified as a cell population showing deviation from normal antigen expression patterns as compared with normal or regenerating marrow. Any level of residual disease was considered MRD^pos. Data are current as of April 1, 2013.

Baseline characteristics of the study cohort are summarized in Table 1. Patients undergoing NMA HCT were significantly older than those undergoing MA HCT (p<0.001), more often were male (p=0.03), had more comorbidities (p<0.001), more often had secondary leukemias (p=0.05), and more often had incomplete blood count recovery at the time of HCT (p<0.001). Sixteen NMA patients (25.4%) and 40 MA patients (19.1%) were MRD^pos, with medians of 0.31% (range: 0.02-2.8%) and 0.29% (0.007-7.8%) abnormal blasts for MRD^pos NMA and MA patients, respectively. Three-year estimates of relapse among NMA patients were 31% (18-44%) and 64% (35-82%) for MRD^neg and MRD^pos patients, respectively, and 21% (15-29%) and 53% (37-68%), respectively, among MA patients (Figure 1A). Among NMA patients, the 3-year estimates of OS were 53% (37-66%) and 49% (21-73%) for MRD^neg and MRD^pos patients, respectively; among MA patients, 3-year OS was estimated to be 74% (65-80%) and 36% (20-51%), respectively (Figure 1B). This unexpectedly similar outcome in OS for MRD^neg and MRD^pos NMA patients was largely accounted for by the considerably higher non-relapse mortality (NRM) in MRD^neg patients (29% [17-42%]) compared to MRD^pos patients (0%), which was the reverse of findings in MRD^neg and MRD^pos MA patients (8% [5-13%] vs. 21% [10-34%], respectively; Figure 1C). Hazard ratio analysis confirmed a highly statistically significant difference between MA and NMA patients in the association of MRD status with NRM (p<0.001), but not with relapse (p=0.45). There was also evidence of a differential association of MRD status with OS (p=0.03). After adjustment for HCT type (NMA vs MA), age, cytogenetic risk, type of AML, number of cycles of induction chemotherapy, type of consolidation therapy, pre-HCT karyotype, pre-HCT blood counts, and HCT-comorbidity index, being MRD^pos was associated with increased risk of relapse (HR=3.31 [1.91-5.73], p<0.001).

The negative impact of MRD on post-transplant relapse risk among AML patients in CR1 undergoing NMA HCT is similar to the negative impact seen in patients undergoing MA HCT. Because of the high rate of NRM among MRD^neg NMA patients the survival difference between MRD^neg and MRD^pos patients was much larger in MA than NMA patients in this analysis.

No relevant conflicts of interest to declare.