Study protocol

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

Virginie Gandemer¹ , Marie-Francoise Auclerc² , Yves Perel³ , Jean-Pierre Vannier⁴ , Edouard Le Gall¹ , Francois Demeocq⁵ , Claudine Schmitt⁶ , Christophe Piguet⁷ , Jean-Louis Stephan⁸ , Odile Lejars⁹ , Marianne Debre¹⁰ , Philippe Jonveaux¹¹ , Jean-Michel Cayuela¹² , Sylvie Chevret¹³ , Guy Leverger¹⁴ , Andre Baruchel² and the FRALLE group

¹Department of Pediatric Hematology, University Hospital of Rennes, Rennes, France

²Department of Pediatric Hematology, University Hospital of St Louis, Paris, France

³Department of Pediatric Hematology, University Hospital of Bordeaux, Bordeaux, France

⁴Department of Pediatric Hematology, University Hospital of Rouen, Rouen, France

⁵Department of Pediatric Hematology, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France

⁶Department of Pediatric Hematology, Nancy University Hospital, Vandoeuvre-les-Nancy, France

⁷Department of Pediatric Hematology, University Hospital of Limoges, Limoges, France

⁸Department of Pediatric Hematology, University Hospital of St Etienne, St Etienne, France

⁹Department of Pediatric Hematology, University Hospital of Tours, Tours, France

¹⁰Department of Pediatric Immunology and Hematology of Necker, Paris, France

¹¹Department of Cytogenetics of University Hospital of Nancy, Nancy, France

¹²Laboratory of Hematology of University Hospital of St Louis, Paris, France

¹³Department of Statistics of St Louis/Université, Paris 7, France

¹⁴Department of Pediatric Hematology, University Hospital of Trousseau, Paris, France

author email corresponding author email

BMC Cancer 2009, 9:14doi:10.1186/1471-2407-9-14

Published:	13 January 2009

Abstract

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).

Conclusion

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.