Improved survival with early intensification: combined results from the Medical Research Council childhood ALL randomised trials, UKALL X and UKALL XI

Abstract

The Medical Research Council (MRC) United Kingdom trial for childhood acute lymphoblastic leukaemia (UKALL X) randomised patients aged 0-14 years inclusive with an initial white blood count of less than 100 × 10 9 /l to receive an early intensification block, a late intensification block, both, or neither. The next trial, UKALL XI, for children aged 1-14 years, randomised between different central nervous system (CNS) directed therapies. At the beginning of the trial, all patients were also randomised between late intensification alone and both early plus late blocks. The effects of both the early and the late block in UKALL X alone have been reported previously. This paper examines the effect of the addition of the early intensification block to treatment which included late intensification, combining the data from UKALL X and the first part of UKALL XI. Early intensification was associated with fewer bone marrow relapses and a reduction in the odds of death of 0.63 (95% confidence interval: 0.46-0.87). Survival was significantly improved with an increase at 5 years of 8%, from 79 to 87%. Following this demonstration that early intensification improves survival, the effect of a third intensification block is under investigation.

A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial

“…33,34 Potential reasons for these neurotoxicities have been reviewed in a previous publication, 34 Overall outcome data from this clinical trial compare favorably with previous POG trials and those of other groups treating children for HR-ALL (62-75%). [9][10][11][12][13][14][15][16][17][18][19][20] Because risk group criteria differ among large cooperative groups treating childhood ALL, external comparisons are difficult and hazardous. However, 66% of the patients in this study would be considered high risk by the CTEP/NCI consensus risk group definition (age у10 years, or WBC у50 000) thus adding some validity to cross comparisons.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20] Increased toxicity was also noted with the aggressive use of myelosuppressive agents. 9,13,14,16,18,[19][20][21][22] However, preliminary results from POG 8698 suggested that early intensification with the less toxic combination of intermediate-dose methotrexate (MTX) and mercaptopurine (MP) might be as effective as the more myelosuppressive combinations used in another POG pilot study (POG 8398) for HR-ALL. 13,17 In 1991, the POG opened a group-wide randomized phase III clinical trial (POG 9006) to treat children with HR-ALL.…”

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

“…The primary diagnosis of leukaemia was made at 3.8 (0.85–15.0) years and 5.6 (1.6–14.1) years of age in the HSCT-TBI survivors and chemotherapy-only survivors, respectively. All subjects were treated according to contemporaneous UK national paediatric leukaemia at the time of their diagnosis including primary protocols UKALL11, UKALL 97/99, and UKALL2003 for ALL [19-21]; AML10 and AML12 for AML [22, 23]; and relapse protocols R1, R2, and R3 for ALL [24-26]. Protocols for ALL consisted of complex regimens of high but variable doses of steroids with prednisolone and/or dexamethasone [19-21, 24-26].…”

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

“…[3][4][5][6][7] The Pediatric Oncology Group (POG, now part of the Children's Oncology Group, COG) investigated six to 12 infusions of intermediate-dose intravenous (i.v.) MTX (1 g/M 2 ) followed by leucovorin rescue at 2-3 week intervals (IDMTX).…”