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Minimal residual disease is an independent predictor for 10-year survival in CLL

Marwan Kwok, Andy C. Rawstron, Abraham Varghese, Paul A. S. Evans, Sheila J. M. O’Connor, Chi Doughty, Darren J. Newton, Paul Moreton and Peter Hillmen

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Presence of residual disease at the end of treatment predicts for long-term PFS and OS independent of prior treatment and cytogenetics. Posttreatment minimal residual disease (MRD) levels were obtained within 6 months after the end of treatment by multiparameter flow cytometry to a sensitivity of 10−4 (0.01%). A patient was considered MRD-negative if the MRD level was below the level of detection (ie, <0.01%). The log-rank P value is displayed, and P < .05 is considered statistically significant. (A) Progression-free survival (PFS) according to the level of detectable disease at the end of treatment. (B) Overall survival (OS) according to the level of detectable disease at the end of treatment. (C) PFS according to prior treatment and the MRD status at the end of treatment. (D) OS according to prior treatment and the MRD status at the end of treatment. (E) PFS according to del(17p) or del(11q) and the MRD status at the end of treatment. (F) OS according to del(17p) or del(11q) and the MRD status at the end of treatment. (E-F) Cytogenetic aberrations were evaluated by fluorescence in situ hybridization. The balance of patients with del(17p) and del(11q), respectively, was comparable between the MRD-negative and MRD-positive groups. In the MRD-negative del(17p/11q) group, 3 of 9 patients (33%) had del(17p), whereas 6 of 9 patients (67%) had del(11q). In the MRD-positive del(17p/11q) group, 6 of 15 patients (40%) had del(17p), whereas 9 of 15 patients (60%) had del(11q). MRD-neg, MRD-negative; MRD-pos, MRD-positive.

Tables

  • Table 1.

    Univariate and multivariate analysis of posttreatment MRD levels with other parameters of prognostic significance

    ParameterProgression-free survivalOverall survival
    Univariate (log-rank) PMultivariate (Cox) PHazard ratio (95% CI)Univariate (log-rank) PMultivariate (Cox) PHazard ratio (95% CI)
    Age* (60 y).513.001.0012.41 (1.45-4.00)
    Hemoglobin* (110 g/L).957.058
    Platelet* (100 × 109/L).001.983.034.168
    Binet stage* (A/B vs C).005.870.001.0182.23 (1.14-4.33)
    Prior treatment (Y/N).003.159.003<.0012.61 (1.61-4.23)
    Treatment type<.001.265.004.886
    IWCLL response<.001.545.001.585
    MRD level (<0.01/0.01-0.1/0.1-1/>1%)<.001<.0012.07 (1.59-2.69)<.001.0021.39 (1.13-1.70)
    Adverse cytogenetics* (del 17p/11q).024.0132.00 (1.16-3.45).051
    • Bold values are statistically significant (P < .05).

    • * Age, hemoglobin, and platelet count; Binet stage; and cytogenetics were assessed at the time of treatment initiation.

    • Cytogenetic aberrations [del(17p) and/or del(11q)] were evaluated by metaphase fluorescence in situ hybridization.