Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study.
BACKGROUND
The dismal prognosis of very-high-risk childhood acute lymphoblastic leukaemia could be improved by allogeneic haemopoietic cell transplantation. We compared this strategy with intensified chemotherapy protocols, with the aim to improve the outcome of children with very-high-risk acute lymphoblastic leukaemia in first complete remission.


METHODS
A cooperative prospective study was set up in seven countries. Very-high-risk acute lymphoblastic leukaemia in first complete remission was defined by the presence of at least one of the following criteria: (1) failure to achieve complete remission after the first four-drug induction phase; (2) t(9;22) or t(4;11) clonal abnormalities; and (3) poor response to prednisone associated with T immunophenotype, white-blood-cell count of 100x10(9)/L or greater, or both. Children were allocated treatment by genetic chance, according to the availability of a compatible related donor, and assigned chemotherapy or haemopoietic-cell transplantation. The primary outcome was disease-free survival and analysis was by intention to treat.


RESULTS
Between April, 1995, and December, 2000, 357 children entered the study, of whom 280 were assigned chemotherapy and 77 related-donor haemopoietic-cell transplantation. 5-year disease-free survival was 40.6% (SE 3.1) in children allocated chemotherapy and 56.7% (5.7) in those assigned transplantation (hazard ratio 0.67 [95% CI 0.46-0.99]; p=0.02); 5-year survival was 50.1% (3.1) and 56.4% (5.9), respectively (0.73 [0.49-1.09]; p=0.12).


CONCLUSIONS
Children with very-high-risk acute lymphoblastic leukaemia benefit from related-donor haemopoietic-cell transplantation compared with chemotherapy. The gap between the two strategies increases as the risk profile of the patient worsens.
Balduzzi
Adriana
A
Clinica Pediatrica dell'Università degli Studi di Milano Bicocca, Ospedale San Gerardo Via Pergolesi 33, 20052 Monza, Milan, Italy. adriana.balduzzi@pediatriamonza.it
Valsecchi
Maria Grazia
MG
Uderzo
Cornelio
C
De Lorenzo
Paola
P
Klingebiel
Thomas
T
Peters
Christina
C
Stary
Jan
J
Felice
Maria S
MS
Magyarosy
Edina
E
Conter
Valentino
V
Reiter
Alfred
A
Messina
Chiara
C
Gadner
Helmut
H
Schrappe
Martin
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous