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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1408-1413.
Prepublished online as a Blood First Edition Paper on October 24, 2006; DOI 10.1182/blood-2006-03-011908.


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Submitted March 22, 2006
Accepted August 21, 2006

Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia - Results of the GRAAPH-2003 study

Adrienne de Labarthe, Philippe Rousselot, Francoise Huguet-Rigal, Eric Delabesse, Francis Witz, Sebastien Maury, Delphine Rea, Jean-Michel Cayuela, Marie-Christine Vekemans, Oumedaly Reman, Agnes Buzyn, Arnaud Pigneux, Martine Escoffre, Yves Chalandon, Elizabeth MacIntyre, Veronique Lheritier, Jean-Paul Vernant, Xavier Thomas, Norbert Ifrah, and Herve Dombret*

Department of Hematology, Hopital Saint-Louis, Paris, France
Department of Hematology, Hopital Andre Mignot, Versailles, France
Department of Hematology, Hopital Purpan, Toulouse, France
Department of Hematology, Hopital Necker, Paris, France
Department of Hematology, Hopital de Brabois, Nancy, France
Department of Hematology, Hopital Henri Mondor, Creteil, France
Department of Hematology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium
Department of Hematology, Centre Hospitalier Universitaire, Caen, France
Department of Hematology, Hopital Haut-Leveque, Pessac, France
Department of Hematology, Centre Hospitalier Universitaire, Rennes, France
Department of Hematology, Hopital Universitaire, Geneve, Switzerland
Department of Hematology, Hopital Edouard Herriot, Lyon, France
Department of Hematology, Hopital Pitie-Salpetriere, Paris, France
Department of Hematology, Centre Hospitalier Universitaire, Angers, France

* Corresponding author; email: herve.dombret{at}sls.ap-hop-paris.fr.

Combination of imatinib with chemotherapy has been recently reported as very promising in patients with Ph+ ALL. During 2004 and 2005, 45 patients with newly-diagnosed Ph+ ALL were treated in the GRAAPH-2003 study in which imatinib was started with HAM consolidation in good early responders (cortico- and chemo-sensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (cortico- and/or chemo-resistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL RQ-PCR negativity rates were 96% and 29%, respectively. All the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, estimated cumulative incidence of relapse, disease-free and overall survival were 30%, 51%, and 65%, respectively. These three endpoints compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy which has to be combined with imatinib and carefully re-evaluate the place of allogeneic SCT in this new context.


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