Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980–1997

Abstract

Results of three consecutive completed UK trials (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997) for childhood lymphoblastic leukaemia are presented. National accrual has progressively increased so that over 90% of all the country's ALL cases were treated on the latest trial reported, UKALLXI. From 1980 to 1990, event-free and overall survival progressively improved, following adoption of an American therapy template and use of two post-remission intensification modules. Since 1990 despite demonstration of the benefit of a third intensification module overall event-free survival (EFS) has not improved further. Survival remains high due to a good retrieval rate especially for those relapsing off treatment after receipt of two intensification pulses. Possible reasons for the plateau in event-free survival (including type and dose of induction steroid, dropping of induction anthracycline, type and dose of asparaginase, gaps early in therapy following intensification, and overall lack of compliance in maintenance) are being explored in the latest protocol ALL '97. Cranial irradiation had been successfully replaced by a long course of intrathecal methotrexate injections for the majority of patients. Age (Ͻ1 year Ͼ10 years) sex (male) and white count Ͼ50 × 10 9 /l plus slow initial bone marrow clearance were consistently the most important independent prognostic indicators during this time period. Rome/NCI criteria accurately predict standard and highrisk groups for B cell lineage, but not consistently for T cell disease. This international collaborative venture might help us to define those truly at highest risk, and how we can optimise therapy for specific subgroups including T-ALL and those with unfavourable cytogenetics. Leukemia (2000) 14, 2307-2320.

Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements

“…The failure of higher leukocyte count increments to adversely affect outcome has also been noted in T-cell ALL, [25][26][27][28] another leukemia usually presenting with a high leukemic cell burden. Previous studies have shown that in t(11;19) ALL, T-lineage cases have a more favorable outcome than B-lineage cases.…”

Childhood leukaemia: long-term excess mortality and the proportion ‘cured’

“…The evidence for risk-directed therapy underpinning these huge gains in survival from childhood 1971 -1975 1976 -1980 1981 -1985 1986 -1990 1991 -95 1996 -2000 Average annual change a Childhood, 1986;Eden et al, 2000;Gibson et al, 2005). All the studies that have examined long-term survival in childhood cancer patients, in Britain and in other countries, have concluded that survivors experienced excess mortality beyond 5 years after diagnosis, with a 10.8-fold excess in all-cause mortality in the United States and Nordic countries (Hawkins, 1989;Robertson et al, 1994;Mertens et al, 2001;Möller et al, 2001;Cardous-Ubbink et al, 2004).…”

“…The increase in survival is attributed to the use of intensive chemotherapy, combined with other modalities of treatment, and to improved supportive care (Eden et al, 2000;Gibson et al, 2005). The number of childhood leukaemia survivors who are alive more than 10 years after diagnosis has increased as a result, and there are currently over 5500 long-term survivors in Great Britain.…”

Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia

“…Current chemotherapy treatment protocols induce complete remission (CR) in Ͼ95% of children with ALL and disease-free survival (DFS) rates are exceeding 70%. [1][2][3][4][5] The patients are considered to be in morphological remission when blast cells compose less than 5% of the bone marrow (BM) cell population. However, relapses of disease do occur, suggesting that some of the leukemic blasts are resistant to chemotherapy and can persist in very small amounts in the BM.…”