Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study.
BACKGROUND
We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors.


METHODS
Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling.


RESULTS
Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 +/- 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm3 and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 +/- 14% and 33 +/- 15%, respectively).


CONCLUSIONS
Age, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.
Gandemer
Virginie
V
Department of Pediatric Hematology, University Hospital of Rennes, Rennes, France. virginie.gandemer@chu-rennes.fr
Auclerc
Marie-Francoise
MF
Perel
Yves
Y
Vannier
Jean-Pierre
JP
Le Gall
Edouard
E
Demeocq
Francois
F
Schmitt
Claudine
C
Piguet
Christophe
C
Stephan
Jean-Louis
JL
Lejars
Odile
O
Debre
Marianne
M
Jonveaux
Philippe
P
Cayuela
Jean-Michel
JM
Chevret
Sylvie
S
Leverger
Guy
G
Baruchel
Andre
A
D000208:Acute Disease; D000293:Adolescent; D000367:Age Factors; D018943:Anthracyclines; D000971:Antineoplastic Combined Chemotherapy Protocols; D001215:Asparaginase; D001549:Benzamides; D001853:Bone Marrow / Q000187:drug effects*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003348:Cortisone; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D011241:Prednisone / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D012008:Recurrence; D016896:Treatment Outcome; D014750:Vincristine; D055815:Young Adult
D018943:Anthracyclines; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014750:Vincristine; D000068877:Imatinib Mesylate; D001215:Asparaginase; D003348:Cortisone; D011241:Prednisone