Outcome after first relapse in childhood acute lymphoblastic leukaemia – lessons from the United Kingdom R2 trial

Abstract

SummaryA retrospective analysis of children with first relapse of acute lymphoblastic leukaemia (ALL), treated on the UKALL R2 protocol at four different hospitals, between June 1995 and December 2002 was performed. Of the 150 children 139 (93%) achieved a second complete remission. The overall survival (OS) and event-free survival (EFS) for the whole group was 56% and 47% respectively. The duration of first complete remission and immunophenotype, but not sites of relapse, were predictive for survival. Using the Berlin-Frankfürt-Münster risk stratification for relapsed ALL, the OS and EFS for standard, intermediate (IR) and high risk (HR) groups were 92% and 92%, 64% and 51%, and 14% and 15%, respectively; P < 0AE0001 for both OS and EFS. In the IR group, those with a very early isolated central nervous system relapse also had a significantly worse outcome (P ¼ 0AE0001). Given the poor outcome of a second relapse, clear strategies are required to identify those in the IR group who will most benefit from stem cell transplantation (SCT). A higher proportion (16%) of induction failures in the HR group suggest the need for novel agents during this phase of treatment, but SCT was associated with a lower relapse rate and better outcome than those treated with chemotherapy alone.

Survival following relapse in childhood haematological malignancies diagnosed in 1974–2003 in Yorkshire, UK

“…Our findings indicate that 30% of leukaemia and 20% of lymphoma patients are likely to relapse at least once. Time to first relapse was similar for ALL and Hodgkin's lymphoma, although somewhat shorter for AML, other leukaemia subtypes and NHL, but accorded with previous ALL reports (Gustafsson et al, 1987(Gustafsson et al, , 2000Eden et al, 2000;Lawson et al, 2000;Schrappe et al, 2000;Silverman et al, 2000;Tsuchida et al, 2000;Vilmer et al, 2000;Chessells et al, 2003;Roy et al, 2005). There was no change in the median time to relapse for any diagnostic group across the study period, which therefore did not confirm local impressions that more children were surviving longer at the expense of more frequent relapses.…”

“…Most literature on relapse concerns acute lymphoblastic leukaemia (ALL), and is almost entirely limited to patients either on a trial protocol or selected from a hospital-based series (Eden et al, 2000;Gustafsson et al, 2000;Lawson et al, 2000;Schrappe et al, 2000;Silverman et al, 2000;Tsuchida et al, 2000;Vilmer et al, 2000;Chessells et al, 2003;Roy et al, 2005), although one paper from Scandinavia has reported on the outcome following relapse ALL in a populationbased cohort (Schroeder et al, 1995). A smaller number of studies have focused on relapse associated with acute myeloid leukaemia (Caspers and Creutzig, 2005;Gibson et al, 2005;Lie et al, 2005).…”

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

“…Modern therapy has increased event-free survival, but late relapse still occurs (Vora et al, 1998;Lawson et al, 2000;Roy et al, 2005;Feltbower et al, 2007), although it can be unclear whether this is a 'true' relapse of the original leukaemia or the occurrence of a second similar malignancy. It has been postulated, for example, that a persistent preleukaemic clone may survive chemotherapy for the original disease and later lead to a second, similar leukaemia, after further events induce disease progression (Vora et al, 1998).…”

Acute Lymphoblastic Leukemia: What Have We Learned About the Effects of This Disease and Its Treatment on the Nervous System?

“…With current treatment regimens, isolated CNS relapse has been reduced to <5% of pediatric cases of ALL (Laningham et al, 2007;Reiter et al, 1994). CNS relapse accounts for approximately 30-40% initial relapses (Henze et al, 1991;Roy et al, 2005;Gaynon et al, 1998). CNS relapses can occur isolated, or in combination with bone marrow relapse.…”