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

• Published in: The Lancet (British edition) 1998-11, Vol.352 (9142), p.1731-1738
• Main Authors: van Dongen, Jacques JM, Seriu, Taku, Panzer-Grümayer, E Renate, Biondi, Andrea, Pongers-Willemse, Marja J, Corral, Lilly, Stolz, Frank, Schrappe, Martin, Masera, Giuseppe, Kamps, Willem A, Gadner, Helmuth, van Wering, Elisabeth R, Ludwig, Wolf-Dieter, Basso, Giuseppe, de Bruijn, Marianne AC, Cazzaniga, Giovanni, Hettinger, Klaudia, van der Does-van den Berg, Anna, Hop, Wim CJ, Riehm, Hansjörg, Bartram, Claus R
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone marrow; Bone Marrow - pathology; Child; Children & youth; Disease-Free Survival; Europe; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Medical screening; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Prognosis; Recurrence; Survival Analysis; Treatment Outcome
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(98)04058-6

Sensitive techniques for detection of minimal residual disease (MRD) at degrees of one leukaemic cell per 10 3–10 6 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. 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. 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]