Measurement of minimal residual disease before and after myeloablative hematopoietic cell transplantation for acute leukemia

Multiparameter flow cytometry (MFC) can identify leukemia-associated immunophenotypes in more than 90% of cases of acute leukemia with detection limits of 10−3–10−4. In order to better understand the potential utility of MFC to measure minimal residual disease (MRD) in the setting of myeloablative hematopoietic cell transplantation (HCT), we studied cohorts of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in complete remission (CR) both pre- and post-HCT. Among 253 patients with AML, the 3-year estimates of overall survival were 73% (CR1) and 73% (CR2) for those who were MRDneg and 32% (CR1) and 44% (CR2) for those who were MRDpos, with relapse rates being more than doubled in those who were MRDpos pre-HCT (21% vs 58% for CR1 patients and 19% vs 68% for CR2 patients). The presence of MRD anytime during the first 100 days post-HCT predicted a 6-fold higher risk of subsequent relapse. In 157 patients with ALL, the 3-year overall survivals were 68% for the MRDneg cohort vs 40% for those who were MRDpos pre-HCT, with probabilities of relapse of 16% in those who were MRDneg vs 33% in the MRDpos group. As in AML, the presence of MRD in the post-transplant setting indicated that the risk of subsequent relapse was high, but not inevitable.