Should Stem Cell Transplantation (SCT) Be Recommended for Any Child with AML in 1^st CR?

Between 1988 and 2002, 868 children (0–15 years) were entered into MRC AML 10 (1988–95, n=341) and AML 12 (1995–2002, n=527) trials. Children were allocated to one of three MRC risk groups: good risk - patients with t(8,21),inv(16),t(15,17) irrespective of bone marrow status after course 1 or the presence of other genetic abnormalities; standard risk - patients with neither favourable nor adverse cytogenetics and not more than 15% blasts in the bone marrow after course 1; poor risk - patients with more than 15% blasts in the bone marrow after course 1 or with adverse abnormalities of -5,-7, del(5q), abn(3q), complex (>/-5 abnormalities) and without favourable genetic abnormalities. Outcome from CR - death in CR (DCR), relapse risk (RR), disease-free survival (DFS) and survival from CR (OSCR) - was analysed by MRC risk group.

In AML 10 all patients were eligible for SCT with a histocompatible sibling donor, but unrelated donor transplantation was not part of the protocol. Because of their favourable outcome in AML 10, good risk children were not eligible for SCT in AML 12 and part way through the trial a similar approach was adopted for standard risk patients, whilst SCT continued to be recommended for poor risk patients with their inferior outcome. Both sibling and unrelated donor transplantation were permitted. In AML 10 and AML 12, 38 of 139 (27%) poor risk children underwent SCT - 17 sibling allografts, 11 unrelated donor allografts and 10 autografts. The procedural mortality was: 6%, 55% and 0% respectively. Mantel-Byar analysis (to account for time to SCT) comparing transplanted with non-transplanted poor risk children showed no evidence of reduction in relapse risk (HR 1.02, 95% CI 0.58–1.79, p=0.9), disease-free survival (HR 1.47, 95% CI 0.87–2.50, p=0.16) or survival benefit (HR 1.64, CI 0.94–2.85, p=0.08 against SCT), both overall or for any type of SCT. The survival at 8 years from SCT was 41% for sibling allografts, 18% for unrelated donor allografts and 60% for autografts.

Outcome is relative and, whilst poor risk children still do worse than good and standard risk patients, the outcome for poor risk children has improved. A survival at 8 years from CR of about 50% for poor risk children in AML12 (and no deaths beyond 4 years suggesting that most of those who survive are cured), raises questions as to whether any children with AML should be transplanted in 1^st CR given the mortality and morbidity of the procedure. The high mortality associated with unrelated donor transplantation requires further investigation.