Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia.
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)
Venditti
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Cattedra di Ematologia, Università di Roma Tor Vergata, Divisione di Ematologia, Rome, Italy. adriano.venditti@tin.it
Buccisano
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F
Del Poeta
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G
Maurillo
L
L
Tamburini
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A
Cox
C
C
Battaglia
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A
Catalano
G
G
Del Moro
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B
Cudillo
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L
Postorino
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Masi
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M
Amadori
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S
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