The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the Medical Research Council UKALLR1 study

Abstract

Summary. We have examined the toxicity and overall outcome of the Medical Research Council UKALL R1 protocol for 256 patients with relapsed childhood acute lymphoblastic leukaemia (ALL). Second remission was achieved in over 95% of patients. Two patients died during induction and seven patients died of resistant disease. The overall actuarial event-free survival (EFS) at 5 years for all patients experiencing a ®rst relapse was 46% (95% CI 40± 52). Duration of ®rst remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic signi®cance. Fiveyear EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for those relapsing without bone marrow involvement > 2´5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however, were not comparable with respect to risk factor pro®le, and therefore direct comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatment groups, but did not suggest bene®t for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the dif®culties in running randomized trials especially in patients who have relapsed from a previous trial. The optimal treatment for relapsed ALL therefore remains uncertain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.

Allogeneic bone marrow transplantation for childhood relapsed acute lymphoblastic leukemia: comparison of outcome in patients with and without a matched family donor

“…This result is similar to the overall experience reported in the last 10 years by some, 3,10 but not all 6 other groups. The reported overall outcome of a cohort of relapsed ALL patients is likely to be influenced by a number of factors including duration of follow-up, process of selection of the cohort, rate of attainment of second remission, and intensity of initial treatment received by the patients in first remission, as well as the nature of the therapy delivered to the patients following second remission.…”

“…The finding of no significant difference in outcome between initial early or late relapsing patients appears to differ from the findings of previous studies. 6,10,13 However, these studies report a shorter follow-up than our cohort. The differences in outcome between initial early and late relapsing patients may also become less apparent with further follow-up in those cohorts.…”

“…Further intensification of chemotherapy, often including BMT is the major option. [6][7][8][9][10][11][12][13][14][15][16][17][18] How much advantage BMT in second clinical remission (CR2) offers over intensive chemotherapy alone remains controversial. [8][9][10][11][12][13][14] In particular, it has not been conclusively established whether BMT should be the preferred treatment option for children suffering relapses late after first remission, or at all sites.…”

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…[1][2][3][4][5][6][7][8][9] However, the treatment is still controversial for low-risk relapses, which either involve extramedullary sites only and/or occur late in the BM. [10][11][12][13][14] Autologous transplantation may be an alternative to chemotherapy for ALL in CR2 after low-risk relapse.…”

‘Allogeneic marrow transplantation in children with acute leukemia: a practice whose time has gone’: twenty years later

“…In a UK study by Lawson et al 18 the relative benefit of allo-HCT and continued chemo was determined in a cohort of 246 children with ALL in second remission by matched donor availability comparison. For children allocated to allo-HCT the 7-year event-free survival was 45% and for those assigned to continued chemo it was 39.7%, not a significant difference when adjusted for time to transplant, duration of first remission, marrow involvement at relapse and age at diagnosis (Figure 2).…”