Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study.
The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL real-time quantitative polymerase chain reaction (RQ-PCR) negativity rates were 96% and 29%, respectively. All of the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, the estimated cumulative incidence of relapse, disease-free survival, and overall survival were 30%, 51%, and 65%, respectively. These 3 end points 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 that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context.
de Labarthe
Adrienne
A
Department of Hematology, Hôpital Saint-Louis, Paris, France, and Department of Hematology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.
Rousselot
Philippe
P
Huguet-Rigal
Françoise
F
Delabesse
Eric
E
Witz
Francis
F
Maury
Sébastien
S
Réa
Delphine
D
Cayuela
Jean-Michel
JM
Vekemans
Marie-Christine
MC
Reman
Oumedaly
O
Buzyn
Agnès
A
Pigneux
Arnaud
A
Escoffre
Martine
M
Chalandon
Yves
Y
MacIntyre
Elizabeth
E
Lhéritier
Véronique
V
Vernant
Jean-Paul
JP
Thomas
Xavier
X
Ifrah
Norbert
N
Dombret
Hervé
H
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D016019:Survival Analysis; D014184:Transplantation, Homologous
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D008942:Mitoxantrone