Results of Medical Research Council trial UKALL IX in acute lymphoblastic leukaemia in adults: report from the Medical Research Council Working Party on Adult Leukaemia

Durrant, Ian; Richards, Susan

doi:10.1111/j.1365-2141.1993.tb08649.x

Cited by 38 publications

(13 citation statements)

References 19 publications

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“…As shown in Table 1, where the age-related incidence of ALL is calculated on the results of a national epidemiological survey with central haematological review, there is substantial underrepresentation of older patients in UKALL XA; as there was in the precursor UKALL IX where 80% of the patients were under 40. 6 It is possible that selective entry of older adults to UKALL XA has resulted in an over-estimate of survival chances in this age group. A review of all recent studies of adult ALL with more than 100 patients and follow-up of over 3 years showed that the median age for all patients in these series was 29.…”

Section: Discussionmentioning

confidence: 99%

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The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties

Chessells¹,

et al. 1998

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The purpose of the study was to examine the influence of age on outcome in a large cohort of children and adults with lymphoblastic leukaemia who were treated on two similar trials. Factors influencing outcome were examined in 2204 patients aged over 1 year treated between 1985 and 1992 on the parallel Medical Research Council Trials UKALL X and Xa, for children and adults, respectively. There was a progressive worsening in survival with increasing age from 85% (95% CI 83-87) at 5 years for children aged 1-9 to 24% (CI 17-31) for patients over 40. Induction failures, deaths in remission and bone marrow relapses increased significantly with age. Analysis of clinical and biological features showed dominance of early B-ALL in childhood and increasing incidence of the PhЈ chromosome with age. Over 80% of eligible children, but a much lower proportion of adults especially those over 40, was entered. Compliance was stricter in the paediatric trial but most deviations in adults involved giving more treatment. Analysis of results in a proportional hazards model confirmed the overwhelming independent influence of age; with all other factors equal a 10 year old had half the risk of treatment failure of a 20 year old and a 44 year old double the risk. Selective entry to therapeutic trials and increased treatment-related toxicity are features of adult ALL but age itself remains a dominant prognostic factor. While improved supportive care and refinements of conventional therapy may have some effect on prognosis, new understandings and treatment approaches to adult ALL are needed.

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Section: Discussionmentioning

confidence: 99%

“…MRC UKALL XA succeeded MRC UKALL IX which has been previously reported 6 and was open to all adults aged 15 and over in the UK, except those with B-ALL. It ran from April 1985 to December 1992 and all patients have been followed up until October 1996, a maximum of 11. and a minimum of 32 years from diagnosis.…”

Section: Introductionmentioning

confidence: 85%

The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties

Chessells¹,

et al. 1998

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“…The authors concluded that the use of further intensification cycles using different drug combinations might be beneficial. With regard to IDMTX, they reasoned that the dose level had probably been too low, particularly since it was not associated with any morbidity [17].…”

Section: Hdmtx In Adult Allmentioning

confidence: 98%

“…Subsequent administration of LV protecting nonmalignant cells against toxicity of HDMTX Cuttner et al [14] 1991 1 g/m 2 -yes 1 24 30 mg/m 2 !12 i. v. q 6 h Linker et al [39] 1991 0.69 g/m 2 -no 42 0 15 mg/m 2 !12 i. v. q 6 h Elonen et al [18] 1991 3 g/m 2 VCR, DXM or MP no 24 n. r. n. r. Finnish Leuk. Group [25] 1992 3 g/m 2 VCR, P n. r. 4 n. r. 10 mg/m 2 p. o. d 2-4 Wiernick et al [54] 1993 0.1 g/kg VCR, DXM no 6 2 5% of HDMTX dose over 3 days Durrant et al [17] 1993 0.5 g/m 2 -n o ---Amadori et al [3] 1994 1 g/m 2 VCR, AC, DXM no 3 24 15 mg/m 2 !4 i. v. q 6 h 7.5 mg/m 2 !8 p. o. q 6 h Linker et al [40] 1994 2.4 g/m 2 MP no 36 n. r. n. r. Kantarjian et al [36] 1995 1 g/m 2 HD, AC no 24 n. r. n. r.…”

Section: Rationale For Hdmtxmentioning

confidence: 99%

High-dose methotrexate in the treatment of adult acute lymphoblastic leukemia

Gökbuget

Hoelzer

1996

Annals of Hematology

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The application of high-dose treatment elements has an increasing importance in the therapy of acute lymphoblastic leukemia (ALL). High-dose methotrexate (HDMTX) has been introduced in clinical trials more than 20 years ago, since it has several theoretical advantages compared to conventional dose methotrexate. These trials revealed that the efficacy and toxicity of HDMTX depends on features such as dose level, infusion time, combination regimen and schedule of leucovorin rescue. Particularly the application of controlled leucovorin rescue and improved supportive care enabled the application of increasing doses of HDMTX in the treatment of childhood and adult ALL within a variety of schedules and at dose levels mostly ranging between 0.5 g/m2 and 5.0 g/m2. In childhood ALL, first devised to replace CNS irradiation in the prophylaxis of CNS relapse HDMTX has contributed to the reduction of bone marrow relapses particularly in low risk B-lineage ALL. In addition it proved to be an effective therapy element for prophylaxis and treatment of CNS disease. At least in low risk ALL CNS irradiation could be safely replaced by repeated cycles of HDMTX with additional intrathecal therapy. In adult ALL only few of the successful treatment approaches with HDMTX have been investigated up to now. The results indicate that HDMTX has a beneficial effect with regard to overall outcome in adult B-lineage ALL. It provides effective CNS prophylaxis in combination with intrathecal therapy. In mature B-ALL HDMTX proved to be one of the most effective treatment elements and contributed to an impressive improvement of outcome in this subgroup. For T-ALL however sufficient data do not exist either in childhood or in adult ALL. Since HDMTX is an effective treatment element with manageable acute and long-term toxicity, its role in the management of adult ALL should be explored more intensively.

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“…During the study period, three Medical Research Council (MRC) trials of treatment for ALL in patients aged 15 and over were open Ð UKALL IX (Durrant and Richards, 1993), UKALL XA and UKALL XII (Goldstone et al, 1997) Ð and two for AML Ð AML9 (Rees et al, 1996) and AML10 (Hann et al, 1997). The Clinical Trial Service Unit (CTSU) provided Patterns of care and survival for adolescents and young adults with acute leukaemia Ð a population-based study information on patients aged 15Ð29 who were included in these trials.…”

Section: Methodsmentioning

confidence: 99%

Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

et al. 1999

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SummaryWe report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.

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Results of Medical Research Council trial UKALL IX in acute lymphoblastic leukaemia in adults: report from the Medical Research Council Working Party on Adult Leukaemia

Cited by 38 publications

References 19 publications

The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties

The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties

High-dose methotrexate in the treatment of adult acute lymphoblastic leukemia

Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

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