Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial

• Published in: British journal of haematology Vol. 129; no. 6; pp. 734 - 745
• Main Authors: Mitchell, C. D., Richards, S. M., Kinsey, S. E., Lilleyman, J., Vora, A., Eden, T. O. B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-06-2005; Blackwell; Blackwell Publishing Ltd
• Subjects: acute lymphoblastic leukaemia; Adolescent; Age Factors; avascular necrosis; Biological and medical sciences; Central Nervous System - pathology; Child; Child, Preschool; dexamethasone; Dexamethasone - adverse effects; Dexamethasone - therapeutic use; Disease-Free Survival; Female; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; Hematologic and hematopoietic diseases; Hematology; Humans; Infant; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukemic Infiltration - prevention & control; Male; Medical sciences; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prednisolone - adverse effects; Prednisolone - therapeutic use; randomized trial; Recurrence; treatment; Treatment Outcome; United Kingdom; Europe; Human; Antineoplastic agent; Corticosteroid; Dexamethasone; Hematology; Steroid hormone; Acute; randomized trial; Malignant hemopathy; Research; Council; Necrosis; Treatment; Lymphoproliferative syndrome; acute lymphoblastic leukaemia; Adrenal hormone; Clinical trial; Acute lymphocytic leukemia; avascular necrosis; Child; Prednisolone
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2005.05509.x

Summary
Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event‐free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0·0007). Event‐free survival was significantly improved with dexamethasone (84·2% vs. 75·6% at 5 years; P = 0·01), with no evidence of differing effects in any subgroup of patients. The use of 6·5 mg/m2 dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk‐groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.