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Tytuł pozycji:

Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms:minimal residual disease and cure?

Tytuł :
Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms:minimal residual disease and cure?
Autorzy :
Hasselbalch, Hans Carl
Holmström, Morten Orebo
Pokaż więcej
Temat :
Protein Kinase Inhibitors/administration & dosage
Inflammation/diagnosis
Cure
Disease Progression
DNA-hypomethylator
Polycythemia Vera/diagnosis
hemic and lymphatic diseases
Inflammation
Review
Pegylated interferon-alpha2
Combination therapy
MPNs
Ruxolitinib
MRD
Myeloproliferative neoplasms
Myeloproliferative Disorders/diagnosis
Immunologic Surveillance
MPN
Treatment Outcome
Mutation
Vaccination strategies
Neoplasm, Residual
Statins
Minimal residual disease
Journal Article
Humans
Interferon-alpha/administration & dosage
Źródło :
Seminars in Immunopathology
Hasselbalch, H C & Holmström, M O 2019, ' Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms : minimal residual disease and cure? ', Seminars in Immunopathology, vol. 41, no. 1, pp. 5-19 . https://doi.org/10.1007/s00281-018-0700-2
Wydawca :
Springer Berlin Heidelberg, 2018.
Rok publikacji :
2018
Oryginalny identyfikator :
pmc: PMC6323070
pmid: 30203226
Opis pliku :
application/pdf
Język :
English
ISSN :
1863-2300
1863-2297
DOI :
10.1007/s00281-018-0700-2
The first clinical trials of the safety and efficacy of interferon-alpha2 (IFN-alpha2) were performed about 30 years ago. Since then, several single-arm studies have convincingly demonstrated that IFN-alpha2 is a highly potent anti-cancer agent in several cancer types but unfortunately not being explored sufficiently due to a high toxicity profile when using non-pegylated IFN-alpha2 or high dosages or due to competitive drugs, that for clinicians at first glance might look more attractive. Within the hematological malignancies, IFN-alpha2 has only recently been revived in patients with the Philadelphia-negative myeloproliferative neoplasms-essential thrombocytosis, polycythemia vera, and myelofibrosis (MPNs)-and in patients with chronic myelogenous leukemia (CML) in combination with tyrosine kinase inhibitors. In this review, we tell the IFN story in MPNs from the very beginning in the 1980s up to 2018 and describe the perspectives for IFN-alpha2 treatment of MPNs in the future. The mechanisms of actions are discussed and the impact of chronic inflammation as the driving force for clonal expansion and disease progression in MPNs is discussed in the context of combination therapies with potent anti-inflammatory agents, such as the JAK1-2 inhibitors (licensed only ruxolitinib) and statins as well. Interferon-alpha2 being the cornerstone treatment in MPNs and having the potential of inducing minimal residual disease (MRD) with normalization of the bone marrow and low-JAK2V617F allele burden, we believe that combination therapy with ruxolitinib may be even more efficacious and hopefully revert disease progression in many more patients to enter the path towards MRD. In patients with advanced and transforming disease towards leukemic transformation or having transformed to acute myeloid leukemia, "triple therapy" is proposed as a novel treatment modality to be tested in clinical trials combining IFN-alpha2, DNA-hypomethylator, and ruxolitinib. The rationale for this "triple therapy" is given, including the fact that even in AML, IFN-alpha2 as monotherapy may revert disease progression. We envisage a new and bright future with many more patients with MPNs obtaining MRD on the above therapies. From this stage-and even before-vaccination strategies may open a new horizon with cure being the goal for some patients.
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