Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

Autor: M Schrappe, A Pannunzio, E D'Aniello, K. Fasching, T Seriu, E R Panzer-Grümayer, Andrea Biondi, MJ Willemse, Jjm van Dongen, W. A. Kamps, Claus R. Bartram, Helmut Gadner, MG Valsecchi
Přispěvatelé: University of Groningen, Biondi, A, Valsecchi, M, Seriu, T, D'Aniello, E, Willemse, M, Fasching, K, Pannunzio, A, Gadner, H, Schrappe, M, Kamps, W, Bartram, C, van Dongen, J, Panzer-Grümayer, E, Immunology
Rok vydání: 2000
Předmět:
Oncology
Cancer Research
Neoplasm
Residual
gene rearrangements
CHILDREN
THERAPY
Cohort Studies
Retrospective Studie
Recurrence
Risk Factors
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
Odds Ratio
Child
Clinical Trials as Topic
INDUCTION
Remission Induction
REARRANGEMENTS
Hematology
CHEMOTHERAPY
Precursor Cell Lymphoblastic Leukemia-Lymphoma
REGIONS
Burkitt Lymphoma
PROGNOSTIC VALUE
Treatment Outcome
END
Risk assessment
Human
medicine.medical_specialty
Risk Assessment
Disease-Free Survival
Follow-Up Studie
childhood ALL
Acute lymphocytic leukemia
Internal medicine
medicine
Humans
Retrospective Studies
Antineoplastic Combined Chemotherapy Protocol
Proportional hazards model
business.industry
Risk Factor
Case-control study
Retrospective cohort study
Odds ratio
Gene rearrangement
medicine.disease
Minimal residual disease
B cell precursor ALL
Case-Control Studies
Immunology
IMMUNOGLOBULIN
TEL
minimal residual disease
Cohort Studie
T cell receptor
business
Follow-Up Studies
Zdroj: Leukemia, 14(11), 1939-1943. Nature Publishing Group
Leukemia, 14, 1939-1943. Nature Publishing Group
ISSN: 0887-6924
Popis: The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case control study was performed in patients classified and treated as medium (or intermediate)-risk according to the criteria of national studies (ALL-BFM 90, DCLSG protocol ALL-8, AIEOP-ALL 91), which includes a good day 7 treatment response. Standardized polymerase chain reaction (PCR) analysis of patient-specific immunoglobulin and T cell receptor gene (TCR) rearrangements were used as targets for semiquantitative estimation of MRD levels: greater than or equal to 10(-2), 10(-3), less than or equal to 10(-4) Twenty-nine relapsing ALL patients were matched with the same number of controls by using white blood cell count (WBC), age, sex, and time in first complete remission, as matching factors. MRD was evaluated at time-point 1 (end of protocol Ia of induction treatment, ie 6 weeks from diagnosis) and time-point 2 (before consolidation treatment, ie 3 months from diagnosis). MRD-based high risk patients (greater than or equal to 10(-3) at both time-points) were more frequently present in the relapsed cases than in controls (14 vs 2), while MRD-based low risk patients (MRD negative at both time-points) (1 vs 18) showed the opposite distribution. MRD-based high risk cases experienced a significantly higher relapse rate than all other patients, according to the estimated seven-fold increase in the odds of failure, and a much higher rate than MRD-based low risk patients (OR = 35.7; P = 0.003). Using the Cox model, the prediction of the relapse-free interval at 4 years was 44.7%, 76.4% and 97.7% according to the different MRD categories. MRD-based risk group classification demonstrate their clinical relevance within the medium-risk B cell precursor ALL which account for the largest number of unpredictable relapses, despite the current knowledge about clinical and biological characteristics at diagnosis. Therefore, MRD detection during the first 3 months of follow-up can provide the tools to target more intensive therapy to those patients at true risk of relapse.
Databáze: OpenAIRE
Externí odkaz: