A revised definition for cure of childhood acute lymphoblastic leukemia.
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).
1] Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA [2] Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
C H
CH
Pui
Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
D
D
Pei
Centre for Translational Medicine, National University of Singapore, Singapore, Singapore.
D
D
Campana
Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA.
C
C
Cheng
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
J T
JT
Sandlund
Department of Pediatrics, University of North Texas Health Science Center, Fort Worth, TX, USA.
W P
WP
Bowman
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
M M
MM
Hudson
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
R C
RC
Ribeiro
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
S C
SC
Raimondi
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
S
S
Jeha
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
S C
SC
Howard
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
D
D
Bhojwani
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
H
H
Inaba
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
J E
JE
Rubnitz
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
M L
ML
Metzger
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
T A
TA
Gruber
Centre for Translational Medicine, National University of Singapore, Singapore, Singapore.
E
E
Coustan-Smith
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
J R
JR
Downing
Department of Bone Marrow Transplantation and Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.
W H
WH
Leung
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
M V
MV
Relling
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
W E
WE
Evans
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009026:Mortality; D016609:Neoplasms, Second Primary; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome