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 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.
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 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.
Authors: M D Tabernero; A M Bortoluci; I Alaejos; M C López-Berges; A Rasillo; R García-Sanz; M García; J M Sayagués; M González; G Mateo; J F San Miguel; A Orfao Journal: Leukemia Date: 2001-03 Impact factor: 11.528
Authors: H M Kantarjian; S O'Brien; T L Smith; J Cortes; F J Giles; M Beran; S Pierce; Y Huh; M Andreeff; C Koller; C S Ha; M J Keating; S Murphy; E J Freireich Journal: J Clin Oncol Date: 2000-02 Impact factor: 44.544
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Authors: María-Belén Vidriales; José J Pérez; Maria Consuelo López-Berges; Norma Gutiérrez; Juana Ciudad; Paulo Lucio; Lourdes Vazquez; Ramón García-Sanz; Maria Consuelo del Cañizo; Javier Fernández-Calvo; Fernando Ramos; M Jesús Rodríguez; M José Calmuntia; Ana Porwith; Alberto Orfao; Jesús F San-Miguel Journal: Blood Date: 2003-02-13 Impact factor: 22.113
Authors: Deborah A Thomas; Stefan Faderl; Jorge Cortes; Susan O'Brien; Francis J Giles; Steven M Kornblau; Guillermo Garcia-Manero; Michael J Keating; Michael Andreeff; Sima Jeha; Miloslav Beran; Srdan Verstovsek; Sherry Pierce; Laurie Letvak; August Salvado; Richard Champlin; Moshe Talpaz; Hagop Kantarjian Journal: Blood Date: 2003-10-09 Impact factor: 22.113
Authors: J Gabert; E Beillard; V H J van der Velden; W Bi; D Grimwade; N Pallisgaard; G Barbany; G Cazzaniga; J M Cayuela; H Cavé; F Pane; J L E Aerts; D De Micheli; X Thirion; V Pradel; M González; S Viehmann; M Malec; G Saglio; J J M van Dongen Journal: Leukemia Date: 2003-12 Impact factor: 11.528
Authors: E Beillard; N Pallisgaard; V H J van der Velden; W Bi; R Dee; E van der Schoot; E Delabesse; E Macintyre; E Gottardi; G Saglio; F Watzinger; T Lion; J J M van Dongen; P Hokland; J Gabert Journal: Leukemia Date: 2003-12 Impact factor: 11.528
Authors: J Takeuchi; T Kyo; K Naito; H Sao; M Takahashi; S Miyawaki; K Kuriyama; S Ohtake; F Yagasaki; H Murakami; N Asou; T Ino; T Okamoto; N Usui; M Nishimura; K Shinagawa; T Fukushima; H Taguchi; T Morii; S Mizuta; H Akiyama; Y Nakamura; T Ohshima; R Ohno Journal: Leukemia Date: 2002-07 Impact factor: 11.528
Authors: S Nishiwaki; K Imai; S Mizuta; H Kanamori; K Ohashi; T Fukuda; Y Onishi; S Takahashi; N Uchida; T Eto; H Nakamae; T Yujiri; S Mori; T Nagamura-Inoue; R Suzuki; Y Atsuta; J Tanaka Journal: Bone Marrow Transplant Date: 2015-09-21 Impact factor: 5.483
Authors: José Luis Piñana; Jaime Sanz; Alessandra Picardi; Christelle Ferrá; Rodrigo Martino; Pere Barba; Marta Gonzalez-Vicent; María Jesús Pascual; Carmen Martín; Amparo Verdeguer; Cristina Diaz de Heredia; Pau Montesinos; José-María Ribera; Miguel Sanz; William Arcese; Guillermo Sanz Journal: Haematologica Date: 2013-10-04 Impact factor: 9.941