title: Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia.
abstract: We used flow cytometry to quantify minimal residual disease (MRD) in 56 patients with acute myeloid leukemia (AML) expressing a leukemia-associated phenotype. Thirty-four patients aged 18 to 60 years were entered into the AML-10 protocol (induction, consolidation, and autologous stem-cell transplantation [ASCT]), whereas 22 patients older than 60 years received the AML-13 protocol (induction, consolidation, and consolidation II). After induction, the level of MRD that was best associated with treatment outcome was 4.5 x 10(-4) residual leukemic cells. However, the outcome in patients with at least 4.5 x 10(-4) cells (n = 26) was not significantly different from that in patients with fewer leukemic cells (n = 30); there were 15 (58%) relapses in the first group and 12 (40%) relapses in the second. After consolidation, the most predictive MRD cutoff value was 3.5 x 10(-4) cells: 22 patients had an MRD level of 3.5 x 10(-4) cells or higher and 17 (77%) of these patients had relapse, compared with 5 of 29 patients (17%) with lower MRD levels (P <.001). An MRD level of 3.5 x 10(-4) cells or higher after consolidation was significantly correlated with poor or intermediate-risk cytogenetic findings, a multidrug resistance 1 (MDR1) phenotype, short duration of overall survival, and short duration of relapse-free survival (P =.014,.031,.00022, and.00014, respectively). In multivariate analysis, this MRD status was significantly associated with a high frequency of relapse (P <.001) and a short duration of overall (P =.025) and relapse-free survival (P =.007). ASCT did not alter the prognostic effect of high MRD levels after consolidation: the relapse rate after transplantation was 70%. Thus, we found that an MRD level of 3.5 x 10(-4) cells or higher at the end of consolidation strongly predicts relapse and is significantly associated with an MDR1 phenotype and intermediate or unfavorable cytogenetic findings. (Blood. 2000;96:3948-3952)
authors.affiliation: Cattedra di Ematologia, Università di Roma Tor Vergata, Divisione di Ematologia, Rome, Italy. adriano.venditti@tin.it
authors.forename: A
authors.initials: A
authors.lastname: Venditti
authors.forename: F
authors.initials: F
authors.lastname: Buccisano
authors.forename: G
authors.initials: G
authors.lastname: Del Poeta
authors.forename: L
authors.initials: L
authors.lastname: Maurillo
authors.forename: A
authors.initials: A
authors.lastname: Tamburini
authors.forename: C
authors.initials: C
authors.lastname: Cox
authors.forename: A
authors.initials: A
authors.lastname: Battaglia
authors.forename: G
authors.initials: G
authors.lastname: Catalano
authors.forename: B
authors.initials: B
authors.lastname: Del Moro
authors.forename: L
authors.initials: L
authors.lastname: Cudillo
authors.forename: M
authors.initials: M
authors.lastname: Postorino
authors.forename: M
authors.initials: M
authors.lastname: Masi
authors.forename: S
authors.initials: S
authors.lastname: Amadori
mesh_terms: D000206:Actuarial Analysis; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003131:Combined Modality Therapy; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D019450:Genes, MDR; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy / Q000628:therapy; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome