Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final resullts 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...

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Detalles Bibliográficos
Autores: Ribera, JM, Oriol, A, Gonzalez, M, Vidriales, B, Brunet, S, Esteve, J, del Potro, E, Rivas, C, Moreno, MJ, Tormo, M, Martin-Reina, V, Sarra, J, Parody, R, de Oteyza, JP, Bureo, E, Bernal, MT
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p12907
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=12907
Access Level:acceso abierto
Palabra clave:acute lymphoblastic leukemia
Philadelphia chromosome
BCR-ABL
imatinib
intensive chemotherapy
stem cell transplantation
imatinib maintenance
Descripción
Sumario: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. Design and 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 Sow 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.