TY - JOUR
T1 - Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia
T2 - Results of the Medical Research Council ALL 97 trial
AU - Roy, Anindita
AU - Bradburn, Mike
AU - Moorman, Anthony V.
AU - Burrett, Julie
AU - Love, Sharon
AU - Kinsey, Sally E.
AU - Mitchell, Chris
AU - Vora, Ajay
AU - Eden, Tim
AU - Lilkyman, John S.
AU - Hann, Ian
AU - Saha, Vaskar
PY - 2005/4
Y1 - 2005/4
N2 - 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 (CR1) 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 × 109/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 CR1 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 CR1.
AB - 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 (CR1) 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 × 109/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 CR1 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 CR1.
KW - Acute lymphoblastic leukaemia
KW - Childhood
KW - Clinical trials
KW - Philadelphia chromosome
UR - http://www.scopus.com/inward/record.url?scp=20244373046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20244373046&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2005.05425.x
DO - 10.1111/j.1365-2141.2005.05425.x
M3 - Article
C2 - 15801953
AN - SCOPUS:20244373046
SN - 0007-1048
VL - 129
SP - 35
EP - 44
JO - British journal of haematology
JF - British journal of haematology
IS - 1
ER -