Abstract
Acute lymphoblastic leukaemia (ALL) has a poorer outcome in children with Down syndrome (DS) which has been attributed in the past to a higher incidence of infective death in remission and late relapses. We report on the outcome of children with DS enrolled on the UK Medical Research Council trial for childhood ALL, MRC ALL 97, between January 1997 and June 2002. Thirty seven children had DS (2%), of whom three were treated on the high risk protocol (HR1). Thirty-three (89%) achieved complete remission at the end of induction, 3 died during induction (8%), and one died later without remission. The median follow up was 4.9 years (2.4–7.8). The 5-year event free survival (EFS: 48.0%, SD 8.9) was not an improvement on the previous MRC UKALL XI trial (57.9%, SD 8.0, p=0.2) and was significantly worse than for children without DS (p<0.00005). At the time of follow up, 46% of the children had died (n=17). Five patients suffered relapse, and the relapse rate was not significantly different from those without DS. One patient known to have cardiac disease died during maintenance due to arrhythmia and 8 died of infection, resulting in a significantly higher rate of death in remission (28%) than in children without DS (3%, p<0.00005). Infective deaths were associated with intensification therapy, except in one child who died during interim maintenance. It was possible to isolate a microorganism in 50% of the cases (two cases of Pseudomonas, one Staphylococcus aureus, one Staphylococcus epidermidis and yeast) plus Rhinovirus was found in a nasopharyngeal aspirate of a fifth case with clinical evidence of bacterial sepsis. For the randomised comparisons (prednisolone versus dexamethasone n=30, mercaptopurine versus thioguanine n=23), results within the DS patients were not significantly different from those in all patients, with benefit for dexamethasone. The increase in remission deaths with DS was greater with prednisolone, and with mercaptopurine (p for interaction = 0.0002, <0.00005, respectively). The revision of the trial in 1999 which adopted the template of CCG 1952 which improved EFS, did so for DS patients also, with no change in the DS remission death rate. In conclusion, children with DS may benefit from increased treatment intensity but still have an unacceptably high rate of infective death in remission.
The common TEL/AML1 rearrangement does not represent a frequent event in acute lymphoblastic leukaemia occurring in children with Down syndrome
