title: How has the management of Ph+acute lymphoblastic leukemia (ALL) changed over the years.
abstract: For decades, Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been considered the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL and, in the elderly, it accounts for approximately 50% of cases. The introduction of tyrosine kinase inhibitors (TKIs) has led to obtain complete hematologic remissions (CHR) in virtually all patients, to improve disease-free survival and overall survival, and to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT). Thus, the current management of adult Ph+ ALL patients is based on the use of a TKI, with or without systemic chemotherapy, followed by an allo-SCT, which still remains the only curative option. Monitoring of minimal residual disease allowed a better stratification of patients, and also enabled to redefine the role of autologous stem cell transplant for patients who do not have a donor or are unfit for an allo-transplant. The main clinical challenges are today represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, including novel TKIs and/or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered.
authors: Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, "Sapienza" University.
authors: Sabina
authors: S
authors: Chiaretti
authors: Robin
authors: R
authors: Foà
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D060828:Induction Chemotherapy; D009154:Mutation; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D016044:Fusion Proteins, bcr-abl