title: Measurement of minimal residual disease before and after myeloablative hematopoietic cell transplantation for acute leukemia.
abstract: 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 MRD(neg) and 32% (CR1) and 44% (CR2) for those who were MRD(pos), with relapse rates being more than doubled in those who were MRD(pos) 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 MRD(neg) cohort vs 40% for those who were MRD(pos) pre-HCT, with probabilities of relapse of 16% in those who were MRD(neg) vs 33% in the MRD(pos) 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, USA; Division of Medical Oncology, University of Washington, School of Medicine, 1100 Fairview Avenue North, D5-310, PO Box 19024, Seattle, WA 98109-1024, USA. Electronic address: fappelba@fhcrc.org.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists
keywords: ALL; AML; CR; CR1; CR2; FISH; GVHD; HCT; MFC; MRD; OS; acute lymphoblastic leukemia; acute myeloid leukemia; complete remission; first complete remission; fluorescence in situ hybridization; graft vs host disease; hematopoietic cell transplantation; immunophenotype; minimal residual disease; multiparameter flow cytometry; overall survival; second complete remission