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 the outcome of children with Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) treated on the national trial for childhood ALL, MRC ALL 97/99, between Jan 1997 and Jun 2002. A diagnosis of Ph+ ALL was made by karyotyping and/or fluorescent in situ hybridisation. Outcome was evaluated according to NCI risk criteria and treatment response. Statistical methods included Kaplan Meier analysis, logrank and stratified logrank tests. Of the 1937 patients treated on the MRC ALL 97/99 protocol, 1836 were successfully screened for Ph chromosome and 42 (2.3%) were positive. This subgroup of patients was heterogeneous at the cytogenetic level with 27 (77%) out of 35 assessable cases having one or more abnormality in addition to the Ph translocation. Four recurrent secondary abnormalities were observed: an extra Ph chromosome, loss of 9p (del 9p), high hyperdiploidy and monosomy 7. The median age at diagnosis and presenting white cell count were 6.8 years and 32.5 × 10⁹/L respectively. 19 (45%) had <25% bone marrow blasts within the first two weeks of treatment and were defined as a Good-response group (GRG), the others were classified as a Poor-response group (PRG). 6/10 (60%) of the patients with an extra Ph chromosome were in the GRG, whereas 8/10 (80%) of those with del 9p belonged to the PRG. 36/42 (86%) achieved complete remission (CR1) at the end of induction of whom 28 underwent bone marrow transplantation (BMT). The median follow up was 41 months (range 21–84 months). The 3-year estimate for event free survival (EFS) (with 95% confidence intervals) was 57% (41–70%). The EFS for the GRG and PRG were 74% (48–88%) and 44% (22–64%) respectively. Significant predictors for survival were presenting white cell count (p=0.02) and early response to treatment (p=0.03), but not age at diagnosis or gender. BMT in CR1 appeared to reduce the risk of a subsequent bone marrow relapse. These results are a significant improvement on previous results, particularly for the PRG. The EFS for the PRG in this report is 44% compared to a 4 yr. EFS of 10% in previously published data from the BFM/AIEOP group. We believe that the early introduction of intensive chemotherapy as in the MRC trial improves early response rates and overall outcome in Ph+ ALL, especially for the PRG. BMT in CR1 is recommended in children with Ph+ ALL, nonetheless newer alternative treatment strategies, such as the use of imatinib mesylate need to be evaluated for children with Ph+ ALL.