title: Tyrosine kinase inhibitors in Ph+ acute lymphoblastic leukaemia: facts and perspectives.
abstract: Two tyrosine kinase inhibitors (TKIs), imatinib and dasatinib, are registered for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) in adults. Other two TKIs (nilotinib and ponatinib) have been tested in the second-line, can offer an alternative in the patients who fail the first-line, and can acquire a role also in the first-line. Here, we provide a summary of the reports of TKIs, used alone, and in combination with chemotherapy. TKIs are very effective alone and with corticosteroids and are likely to improve substantially the outcome when they are combined with standard or dose-adapted chemotherapy. While the complete haematologic remission rate is always very high, close to 100 %, the cytogenetic and molecular remission rates are lower, so that TKIs are still considered as a complement to chemotherapy and as a bridge to allogeneic stem cell transplantation (allo-SCT). However, many patients relapse before transplant, and many patients still relapse, even if they have been submitted to allo-SCT. A proper use of TKIs, the introduction of ponatinib, and of "new generation" TKIs should improve further on the outcome of Ph+ ALL.
authors.affiliation: Unit of Blood Diseases and Stem Cell Transplantation, AO Spedali Civili di Brescia, Brescia, Italy. michelemalagola@yahoo.it.|Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy. michelemalagola@yahoo.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, S.Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.affiliation: Department of Hematology/Oncology "L. and A. Seràgnoli", S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000367:Age Factors; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D035703:Therapies, Investigational; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: Acute lymphoblastic leukaemia; Philadelphia chromosome; Target therapy; Tyrosine kinase inhibitors