Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia

  • Monika Brüggemann
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Thorsten Raff
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Thomas Flohr
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Nicola Gökbuget
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Makoto Nakao
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Jo Droese
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Silke Lüschen
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Christiane Pott
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Matthias Ritgen
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Urban Scheuring
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Heinz-August Horst
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Eckhard Thiel
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Dieter Hoelzer
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Claus R. Bartram
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
  • Michael Kneba
    From the Medical Clinic II, University of Kiel, Germany; Institute of Human Genetics, University of Heidelberg, Germany; Medical Clinic II, Department of Hematology, University of Frankfurt, Germany; and Medical Clinic III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.

説明

<jats:title>Abstract</jats:title><jats:p>Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10-4 or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10-4 or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%-63%) represented the intermediate-risk group. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR ALL population who may benefit from individualized treatment.</jats:p>

収録刊行物

  • Blood

    Blood 107 (3), 1116-1123, 2006-02-01

    American Society of Hematology

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