title: Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.
abstract: Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy.
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Vaclava
authors.initials: V
authors.lastname: Polivkova
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and Faculty Hospital, Olomouc, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Rohon
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Institute of Clinical and Experimental Hematology of the 1st Medicine Faculty, Charles University, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Klamova
authors.affiliation: Department of Internal Medicine and Hematology, 3rd Faculty of Medicine and Faculty Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Cerna
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and Faculty Hospital, Olomouc, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Divoka
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Nikola
authors.initials: N
authors.lastname: Curik
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Zach
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and Faculty Hospital, Olomouc, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Novak
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Iuri
authors.initials: I
authors.lastname: Marinov
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and Faculty Hospital, Olomouc, Czech Republic.
authors.forename: Edgar
authors.initials: E
authors.lastname: Faber
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Institute of Clinical and Experimental Hematology of the 1st Medicine Faculty, Charles University, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Machova Polakova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000187:drug effects / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C581634:BCR-ABL1 fusion protein, human; D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl