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
Language English Country United States Media electronic-ecollection
Document type Case Reports, Journal Article, Research Support, Non-U.S. Gov't
PubMed
27214026
PubMed Central
PMC4877000
DOI
10.1371/journal.pone.0155959
PII: PONE-D-16-01993
Knihovny.cz E-resources
- MeSH
- Fusion Proteins, bcr-abl drug effects genetics MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy genetics MeSH
- Adult MeSH
- Precision Medicine MeSH
- Protein Kinase Inhibitors administration & dosage pharmacology MeSH
- Interferon-alpha administration & dosage pharmacology MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage pharmacology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- High-Throughput Nucleotide Sequencing methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fusion Proteins, bcr-abl MeSH
- BCR-ABL1 fusion protein, human MeSH Browser
- Protein Kinase Inhibitors MeSH
- Interferon-alpha MeSH
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.
Faculty of Science Charles University Prague Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
Institute of Hematology L e A Seràgnoli University of Bologna Bologna Italy
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