Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.
The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10(-3). Conventional intensive consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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C
Eckert
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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N
Hagedorn
1] Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School and University Hospital Motol, Prague, Czech Republic [2] CLIP - Childhood Leukemia Investigation Prague, Prague, Czech Republic.
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Sramkova
St Anna Children's Research Institute and Children's Hospital, Medical University of Vienna, Vienna, Austria.
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Mann
St Anna Children's Research Institute and Children's Hospital, Medical University of Vienna, Vienna, Austria.
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R
Panzer-Grümayer
St Anna Children's Research Institute and Children's Hospital, Medical University of Vienna, Vienna, Austria.
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0000000303698515
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Peters
Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland.
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JP
Bourquin
Hospital for Children and Adolescents, Goethe-University Hospital Frankfurt, Frankfurt, Germany.
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Klingebiel
Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany.
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0000000261214737
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Borkhardt
Department of Pediatrics, University of Schleswig-Holstein, Kiel, Germany.
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Cario
Department of Pediatrics, University of Schleswig-Holstein, Kiel, Germany.
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J
Alten
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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G
Escherich
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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K
Astrahantseff
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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Seeger
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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G
Henze
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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von Stackelberg
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008991:Monitoring, Physiologic; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate