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Abstract
Background:
It has been demonstrated that flow cytometric detection of minimal residual disease (MRD) has a prognostic significance in the treatment of patients with acute leukemia. We investigated the significance of flow cytometric MRD detection for the first time in Korea.
Methods:
We analyzed the results of MRD detection in morphologically complete remission bone marrow aspirates from 89 patients with newly-diagnosed or relapsed acute leukemia, in which leukemic cells had cross-lineage antigen expression. Patients were grouped based on MRD frequencies: ≥1.0%, high MRD; <1.0%, low MRD.
Results:
Forty-seven ALL patients consisted of 10 with high and 37 with low MRD levels. Patients with high MRD levels showed a tendency of more frequent relapse than those with low MRD levels (40.0% and 13.5%, respectively) (P=0.08). High MRD group showed a tendency of short relapse-free survival (RFS) and overall survival (OS), although the differences were not statistically significant. Forty-two AML patients consisted of 16 with high and 26 with low MRD levels. There were no correlations between the MRD levels and relapse rate, RFS or OS. AML patients with high MRD levels showed significantly higher rate of unfavorable cytogenetic risk categories and lower rate of favorable risk categories (P=0.03).
Conclusions:
MRD detection by flow cytometric assay of cross-lineage antigen expression would be useful in predicting treatment outcome in patients with ALL rather than AML. We expect that the establishment of the standardization of methods, time to test or antibody combination would be achieved through further trials in this country.
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Fig. 1.
MRD detection in the bone marrow aspirates from an ALL patient at diagnosis (A), and patients with morphological remission (B and C). The leukemia-associated phenotype includes CD13 and CD19 expression. The MRD levels were 4.33% (B) and 0.01% (C).
Abbreviations: PE, phycoerythrin; FITC, fluorescein isothiocynate; MRD, minimal residual disease.
Fig. 2.
Prognostic significance of minimal residual disease (MRD) frequency in bone marrow aspirates after morphological remission in ALL patients. (A) High MRD group showed a tendency of shorter relapse-free survival (RFS) than low MRD group using a cutoff level of 1.0% (P=0.11). (B) High MRD group also showed a tendency of shorter overall survival (OS) than low MRD group (P=0.54).
Table 1.
Monoclonal antibody panel for immunophenotyping of acute leukemia
Table 2.
Characteristics of patients with acute leukemia
| Characteristics | ALL patients (N=47) | AML patients (N=42) | ||
|---|---|---|---|---|
| Age (yr) | 7 (1-62) | 41 (1-69) | ||
| Pediatric/adult | 32/15 | 7/35 | ||
| Sex (M/F) | 33/14 | 25/17 | ||
| Cross-lineage antigen expression∗ | CD13 | 20 | CD7 | 14 |
| CD13 & CD33 | 15 | CD56 & CD19 | 8 | |
| CD33 | 5 | CD56 | 8 | |
| Others† | 7 | CD19 | 4 | |
| Others‡ | 8 | |||
| Cytogenetic risk categories | ||||
| Favorable | 19 | 18 | ||
| Intermediate | 12 | 18 | ||
| Unfavorable | 11 | 4 | ||
| Unknown | 5 | 2 | ||
| Follow-up duration (months) | 14 (3-40) | 12 (3-28) |
Table 3.
Clinical characteristics according to the MRD levels
| MRD group | ALL patients | AML patients | ||||||
|---|---|---|---|---|---|---|---|---|
| N | Relapse (%) | RFS (months) | OS (months) | N | Relapse (%) | RFS (months) | OS (months) | |
| High (≥1.0%) | 10 | 4 (40.0)∗ | 9.9 | 10.9 | 16 | 5 (31.3)† | 8.8 | 9.7 |
| Low (<1.0%) | 37 | 5 (13.5)∗ | 13.3 | 13.8 | 26 | 5 (19.2)† | 9.2 | 12.8 |
| High (≥0.5%) | 14 | 4 (28.6) | 10.0 | 10.6 | 22 | 5 (22.7) | 8.4 | 8.8 |
| Low (<0.5%) | 33 | 5 (15.2) | 13.5 | 14.0 | 20 | 5 (25.0) | 9.4 | 13.6 |
| High (≥0.1%) | 35 | 7 (20.0) | 10.0 | 10.5 | 34 | 7 (20.6) | 8.6 | 9.7 |
| Low (<0.1%) | 12 | 2 (16.7) | 16.7 | 16.9 | 8 | 3 (37.5) | 9.6 | 15.5 |
Table 4.
Distribution of the MRD groups according to the time of sample collection
| MRD group | ALL patients | AML patients | ||
|---|---|---|---|---|
| Post-induction (N=26) | Post-consolidation (N=21) | Post-induction (N=27) | Post-consolidation (N=15) | |
| High (≥1.0%) | 3 | 6 | 9 | 7 |
| Low (<1.0%) | 23 | 15 | 18 | 8 |
Table 5.
Relation between MRD groups and cytogenetic risk categories
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