Table 7:
Summary of Findings of Prognostic Significance of MRD at End of Induction
| Author, Year | MRD Assay | MRD Categorization, % (% of participants) | Variables in Analysis | Relapse Effect Estimate (95% Cl) | P |
|---|---|---|---|---|---|
| Meleshko et al, 201167 | RQ-PCR | MRD+: ≥ 0.0001 (74.6) MRD–: < 0.0001 (25.6) |
MRD, WBC count at diagnosis, immunophenotype, size of spleen, sex | HR 2.41 (NR) | .005 |
| Zhou et al, 200770 | RQ-PCR | High: ≥ 0.001 (86.6) Low: < 0.001 (13.4) |
MRD, risk group,a treatment group | HR 10.6 (6.05–18.55) | .001 |
| Laughton et al, 200566 | Real-time PCR | High: ≥ 0.001 (69.4) Low: < 0.001 (30.6) |
MRD, risk group,b end-induction WBC, end induction Absolute neutrophil count | HR 3.03 (1.20–7.65) | .019 |
| Dworzak et al, 200264 | FCM | MRD+: ≥ 0.01 (40.9) MRD–: < 0.01 (59.1) |
MRD risk at Week 12, BFM risk groupc | HR 14.9 (3.2–66.7) | < .001 |
| Van Dongen et al, 199858 | PCR | High: ≥ 0.01 (7.9) Intermediate: 0.001 (71.2) Low: ≤ 0.0001 (20.9) |
MRD, treatment group,d age, sex, immunophenotype, WBC (continuous), country, MRD-treatment group interaction | Relative relapse rate per 10-fold increase in MRD 1.6 (1.3–.9) | < .001 |
| Cavé et al, 199856,e | PCR | MRD+: ≥ 0.01 MRD–: < 0.01 |
MRD, immunophenotype | HR 10.6f (3.9–28.7) | NR |
| Coustan-Smith et al, 1998, 200057,62,g | FCM | MRD+: ≥ 0.01 (74.5) MRD–: < 0.01 (25.5) |
MRD, age | NR | < .001 |
| MRD, WBC | NR | < .001 | |||
| MRD, Ph+ | NR | < .001 | |||
| MRD, MLL | NR | < .001 | |||
| MRD, either Ph+ or MLL | NR | .004 |
Abbreviations: BFM, Berlin-Frankfurt-Münster; Cl, confidence interval; FCM, flow cytometry; HR, hazard ratio; MLL, adverse genetic feature; MRD, minimal residual disease; NR, not reported; PCR, polymerase chain reaction; RQ-PCR, real-time quantitative PCR; Ph+, Philadelphia chromosome–positive adverse genetic feature; WBC, white blood cell.
Risk group defined as standard- or high-risk on basis of age, WBC, immunophenotype, central nervous system involvement, and mediastinal mass. Treatment group defines treatment on basis of randomization to 1 of 2 asparaginases, or direct-assigned versus randomized to Escherichia coli treatment.
Risk group defined as standard or high risk on basis of National Cancer Institute criteria: age and WBC.
BFM risk group defined as standard-, medium-, or high-risk on basis of prednisone response, WBC, immunophenotype, age, and cytogenetics.
Treatment group defined by presenting leukemic cell mass and prednisone response. Results presented for Time Point 2.
Results of stratified Cox model presented.
Analysis of present (≥ 1.5 × 10−4) versus absent (< 1.5 × 10−4) MRD was also conducted and yielded similar results (HR = 5.3, 95% Cl 2.2–12.6).
Descriptive information available only for MRD results.