A prospective study of minimal residual disease in childhood B‐lineage acute lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive factor of relapse

• Published in: British journal of haematology Vol. 98; no. 1; pp. 140 - 146
• Main Authors: Jacquy, C., Delepaut, B., Van Daele, S., Vaerman, J. L., Zenebergh, A., Brichard, B., Vermylen, C., Cornu, G., Martiat, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.1997; Blackwell
• Subjects: ALL; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Disease-Free Survival; Female; Hematologic and hematopoietic diseases; Humans; Infant; Karyotyping; Leukemia, B-Cell - drug therapy; Leukemia, B-Cell - radiotherapy; Leukemia, B-Cell - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; MRD; Neoplasm, Residual; PCR; Ploidies; Polymerase Chain Reaction; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prognosis; Prospective Studies; Recurrence; Remission Induction; Risk Factors; Survival Analysis; Human; Relapse; Prognosis; Acute; Minimal residual disease; Exploration; Malignant hemopathy; B-Lymphocyte; Polymerase chain reaction; Follow up study; Lymphoproliferative syndrome; Acute lymphocytic leukemia; Molecular biology; Predictive factor; Child
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1997.1792996.x

We prospectively investigated minimal residual disease (MRD) in 51 children with B‐lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93 protocol. PCR follow‐up was performed in children in morphological and cytogenetic complete remission, provided an immunoglobulin (IgH) gene rearrangement could be detected using FR3/JH amplimers. MRD was studied according to our previously described methodology, with a few modifications including the use of a consensus JH probe to control for PCR efficiency variations. Out of the initial 51 patients, 34 were assessable for MRD at the end of induction at the time of analysis. MRD levels were as follows: >1/103 in 26%, 1/103 to 1/104 in 50% and <1/104 or not detectable in 24%. With a median follow‐up of 20 months there were five relapses, all of which occurred in the group of patients with MRD >1/103. To date, none of the patients with MRD 1/103 (good molecular responder) has relapsed. Classification according to molecular response at the end of induction did not correlate with the conventional risks groups: there were no statistically significant differences between good and bad molecular responders. Of particular interest is the absence of correlation between WBC at diagnosis and MRD level at the end of induction. We conclude that classification of patients into good and bad molecular responders using PCR seems to be a better prognostic indicator than conventional risk factors in childhood B‐lineage ALL. Patients with MRD level >1/103 have a particularly poor outcome and should always be considered for alternative therapeutic strategies in the future, whereas in good molecular responders belonging to poor or intermediate risk categories, treatment de‐escalation might be contemplated.