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Haematologica. 2016 Dec;101(12):1544-1552. Epub 2016 Aug 11.

A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study.

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Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, "Sapienza" University of Rome, Italy
Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, "Sapienza" University of Rome, Italy.
GIMEMA Data Center, Rome, Italy.
Institute of Hematology, University of Perugia, Italy.
Hematology Unit, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.
Hematology Unit and Department of Pharmacy Services, Sant'Eugenio Hospital, Rome, Italy.
Hematology Division, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Hematology Unit, Department of Medical Sciences, University of Cagliari, Italy.
Department of Oncology/Hematology, Niguarda Cancer Center, Niguarda Ca' Granda Hospital, Milano, Italy.
Oncohematology Unit A. Tortora Hospital, Pagani, Salerno, Italy.
Division of Hematology and Bone Marrow Transplantation, University Hospital, Udine, Italy.
Department of Biomedical Sciences, University of Sassari, Italy.


In the GIMEMA LAL 0904 protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Fifty-one patients (median age 45.9 years) were enrolled in the final sequential protocol. At the end of induction (day +50), 96% of evaluable patients (n=49) achieved a complete hematologic remission; after consolidation, all were in complete hematologic remission. No deaths in induction were recorded. Overall survival and disease-free survival at 60 months are 48.8% and 45.8%, respectively. At day +50 (end of imatinib induction), a more than 1.3 log-reduction of BCR-ABL1 levels was associated with a significantly longer disease-free survival (55.6%, 95%CI: 39.0-79.3 vs. 20%, 95%CI: 5.8-69.1; P=0.03), overall survival (59.1%, 95%CI: 42.3-82.6 vs. 20%, 95%CI: 5.8-69.1; P=0.02) and lower incidence of relapse (20.5%, 95%CI: 7.2-38.6 vs. 60.0%, 95%CI: 21.6-84.3; P=0.01). Mean BCR-ABL1 levels remained significantly higher in patients who subsequently relapsed. Finally, BCR-ABL1p190 patients showed a significantly faster molecular response than BCR-ABL1p210 patients (P=0.023). Though the study was not powered to evaluate the role of allogeneic stem cell transplant, allografting positively impacted on both overall and disease-free survival. In conclusion, a sequential approach with imatinib alone in induction, consolidated by chemotherapy plus imatinib followed by a stem cell transplant is a feasible, well-tolerated and effective strategy for adult Philadelphia positive acute lymphoblastic leukemia, leading to the best long-term survival rates so far reported. ( identifier: 00458848).


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