TY - JOUR
T1 - Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia
T2 - The NOPHO ALL2008 experience
AU - Ifversen, Marianne
AU - Turkiewicz, Dominik
AU - Marquart, Hanne V.
AU - Winiarski, Jacek
AU - Buechner, Jochen
AU - Mellgren, Karin
AU - Arvidson, Johan
AU - Rascon, Jelena
AU - Körgvee, Lenne Triin
AU - Madsen, Hans O.
AU - Abrahamsson, Jonas
AU - Lund, Bendik
AU - Jonsson, Olafur G.
AU - Heilmann, Carsten
AU - Heyman, Mats
AU - Schmiegelow, Kjeld
AU - Vettenranta, Kim
PY - 2019
Y1 - 2019
N2 -
The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10
−3
at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10
−3
. After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5–47·7) for MRD-positive versus 5·1% (95% CI: 1·3–19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6–51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4–97·2) and 67·4% (95% CI: 50·2–90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.
AB -
The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10
−3
at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10
−3
. After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5–47·7) for MRD-positive versus 5·1% (95% CI: 1·3–19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6–51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4–97·2) and 67·4% (95% CI: 50·2–90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.
KW - acute lymphoblastic leukaemia
KW - children
KW - haematopoietic stem cell transplantation
KW - minimal residual disease
U2 - 10.1111/bjh.15761
DO - 10.1111/bjh.15761
M3 - Journal article
C2 - 30680711
AN - SCOPUS:85060644850
SN - 0007-1048
VL - 184
SP - 982
EP - 993
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 6
ER -