Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood

Autor: Giovanni Cazzaniga, Klaudia Hettinger, M. J. Pongers-Willemse, Giuseppe Basso, Wolf-Dieter Ludwig, Frank Stolz, Jacques J.M. van Dongen, E. Renate Panzer-Grümayer, Wim C. J. Hop, Elisabeth R. van Wering, Claus R. Bartram, Martin Schrappe, Willem Kamps, Andrea Biondi, T Seriu, Marianne Ac de Bruijn, Lilly Corral, Hansjörg Riehm, Helmuth Gadner, Anna van der Does-van den Berg, Giuseppe Masera
Přispěvatelé: Immunology, Epidemiology, Van Dongen, J, Seriu, T, Panzer-Grumayer, E, Biondi, A, Pongers-Willemse, M, Corral, L, Stolz, F, Schrappe, M, Masera, G, Kamps, W, Gadner, H, Van Wering, E, Ludwig, W, Basso, G, De Bruijn, M, Cazzaniga, G, Hettinger, K, Van Der Does-Van Den Berg, A, Hop, W, Riehm, H, Bartram, C, Faculteit Medische Wetenschappen/UMCG
Rok vydání: 1998
Předmět:
Oncology
medicine.medical_specialty
Neoplasm
Residual
Subsequent Relapse
Prognosi
medicine.medical_treatment
T-CELL
DIAGNOSIS
Disease-Free Survival
Bone Marrow
Recurrence
hemic and lymphatic diseases
Internal medicine
Acute lymphocytic leukemia
SUBSEQUENT RELAPSE
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
ACUTE-LEUKEMIA
Child
Survival analysis
Chemotherapy
Acute leukemia
Antineoplastic Combined Chemotherapy Protocol
business.industry
PERSISTENCE
General Medicine
POLYMERASE CHAIN-REACTION
CHEMOTHERAPY
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Prognosis
Minimal residual disease
Survival Analysis
Surgery
IMMUNOLOGICAL MARKER ANALYSIS
body regions
Europe
Treatment Outcome
El Niño
IMMUNOGLOBULIN
CELL RECEPTOR GENES
Lymphoblastic leukaemia
Survival Analysi
business
Human
Zdroj: Lancet (UK), 352, 1731-1738. Elsevier Ltd.
Scopus-Elsevier
LANCET, 352(9142), 1731-1738. ELSEVIER SCIENCE INC
ISSN: 0140-6736
Popis: Background. Sensitive techniques for detection of minimal residual disease (MRD) at degrees of one leukaemic cell per 103-106 cells (10-3-10-6) during follow-up of children with acute lymphoblastic leukaemia (ALL) can provide insight into the effectiveness of cytotoxic treatment. However, it is not yet clear how information on MRD can be applied to treatment protocols. Methods. We monitored 240 patients with childhood ALL who were treated according to national protocols of the International BFM Study Group. 60 patients relapsed and the patients in continuous complete remission (CCR) had a median event-free follow-up of 48 months. Bone-marrow samples were collected at up to nine time points during and after treatment. Standardised PCR analysis of patient-specific immunoglobulin and T-cell receptor gene rearrangements and TAL1 deletions were used as targets for semiquantitative estimation of MRD. Amount of MRD was classed as 10-2 or more, 10-3, and 10-4 or less. Findings. MRD negativity at the various follow-up times was associated with low relapse rates (3-15% at 3 years), but five-fold to ten-fold higher relapse rates (39-86% at 3 years) were found in MRD-positive patients. The distinct degrees of MRD appeared to have independent prognostic value (p [trend] < 0.001) at all separate time points, especially at the first two time points (at the end of induction treatment and before consolidation treatment). At these two time points a high degree of MRD (≥ 10-2) was associated with a three-fold higher relapse rate when compared with patients with a low degree of MRD (≤ 10-4). At later time points (including the end of treatment) even a low degree of MRD was associated with a poor outcome. Positivity in patients in CCR after treatment was rare (< 1%). With the combined MRD information from the first two follow-up time points, it was possible to recognise three different risk groups - 55 (43%) were in a low-risk group and had a 3-year relapse rate of only 2% (95% Cl 0.05-12%); 19 (15%) were in a high-risk group and had a relapse rate of 75% (55-95%); and 55 (43%) were in an intermediate-risk group and had a 3-year relapse rate of 23% (13-36%). Interpretation. Our collaborative MRD study shows that monitoring patients with childhood ALL at consecutive time points gives clinically relevant insight into the effectiveness of treatment. Combined information on MRD from the first 3 months of treatment distinguishes patients with good prognoses from those with poor prognoses, and this helps in decisions whether and how to modify treatment.
Databáze: OpenAIRE
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