Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: results of the Medical Research Council ALL 97 trial

We report on the outcome of children with Philadelphia positive acute lymphoblastic leukaemia (Ph+ ALL) treated on the UK Medical Research Council (MRC) trial for childhood ALL, MRC ALL 97, between January 1997 and June 2002. Forty-two (2.3%) patients were Ph+. Nineteen (45%) had < 25% blasts in bone marrow (BM) within the first 2 weeks of treatment and were defined as a good response group (GRG), the others as a poor response group (PRG). Thirty-six (86%) achieved first complete remission (CRI) at the end of induction, of which 28 underwent BM transplantation (BMT). The median follow-up was 42 months (range, 21-84). The 3-year event-free survival (EFS; 52%, 95% CI, 36-66%) was a considerable improvement on the previous MRC UKALL XI trial (27%). EFS for the GRG and PRG were 68% (43-84%) and 39% (18-59%), respectively (P = 0.03); presenting white cell count < 50 X 10(9)/l (P = 0.02) was predictive for overall survival. Changes in the MRC ALL97 trial within the study period resulted in some Ph+ ALL receiving daunorubicin and either prednisolone or dexamethasone during induction. Though the use of daunorubicin during induction was not a prospective study question, EFS was significantly better for those whose induction included this drug (P = 0.02). Steroid randomization was not stratified for Ph+ ALL patients and was not predictive for EFS. BMT in CRI appeared to reduce the risk of a subsequent BM relapse. These results show significant improvement on previous MRC trials; future therapeutic strategies should include early intensive therapy and BMT in CRI.