Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial.
BACKGROUND
Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph(+) ALL.


METHODS
This was a phase II study of patients with newly diagnosed Ph(+) ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease.


RESULTS
Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively.


CONCLUSIONS
These results confirm that imatinib is an effective first-line treatment for adult Ph(+) ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was limited, mainly because of transplantation-derived complications rather than drug-specific toxicity.
Ribera
Josep-Maria
JM
Department of Hematology of the Hospitals Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain. jribera@iconcologia.net
Oriol
Albert
A
González
Marcos
M
Vidriales
Belén
B
Brunet
Salut
S
Esteve
Jordi
J
Del Potro
Eloy
E
Rivas
Concepción
C
Moreno
Maria-José
MJ
Tormo
Mar
M
Martín-Reina
Victoria
V
Sarrá
Josep
J
Parody
Ricardo
R
de Oteyza
Jaime Pérez
JP
Bureo
Encarna
E
Bernal
Maria-Teresa
MT
D000293:Adolescent; D000328:Adult; D001549:Benzamides; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D033581:Stem Cell Transplantation / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate