Long-acting interferon for myeloproliferative neoplasms - an update

Pai, Sachin; Kaplan, Jason; Giles, Francis J.

doi:10.1080/17474086.2016.1231571

Cited by 7 publications

(6 citation statements)

References 22 publications

(21 reference statements)

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“…Rare complete long-term remissions post-IFN treatment were reported in a subset of patients who were treated without allogeneic stem cell transplantation (SCT), making this the standard of care for the treatment of CML prior to the era of tyrosine kinase inhibitors (TKIs) ( 18 ). IFN has also been used clinically in the treatment of Philadelphia chromosome (Ph)-negative MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) ( 19 , 20 ). While successful as the first biologic treatment in cancer, the mechanism of action of IFN-α in the treatment of MPN, or its effects on hematopoiesis in general, remained elusive.…”

Section: Type I Ifns (Ifn-α/ifn-β)mentioning

confidence: 99%

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells

2017

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Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to deactivate this response and return to steady state. Prolonged or excessive exposure to inflammatory cytokines, such as in prolonged infection or in chronic rheumatologic conditions, can lead to continued HSC cycling and eventual HSC loss. This promotes bone marrow failure, and can precipitate preleukemic states or leukemia through the acquisition of genetic and epigenetic changes in HSCs. This can occur through the initiation of clonal hematopoiesis, followed by the emergence preleukemic stem cells (pre-LSCs). In this review, we describe the roles of multiple inflammatory signaling pathways in the generation of pre-LSCs and in progression to myelodysplastic syndrome (MDS), myeloproliferative neoplasms, and acute myeloid leukemia (AML). In AML, activation of some inflammatory signaling pathways can promote the cycling and differentiation of LSCs, and this can be exploited therapeutically. We also discuss the therapeutic potential of modulating inflammatory signaling for the treatment of myeloid malignancies.

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Section: Type I Ifns (Ifn-α/ifn-β)mentioning

confidence: 99%

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells

2017

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“…Low dose ASA has been frequently used during pregnancy and it is considered safe for the fetus without a significant risk of bleeding for the mother [18]. Due to the increased percentage of abortions and pregnancy complications in untreated patients as results of thrombosis and abnormal placenta blood circulation, the addition of low-dose ASA showed encouraging results.…”

Section: Low Dose Aspirin and Other Antiplatelet Agentsmentioning

confidence: 85%

“…Pregnant women who are candidates for platelet-lowering therapy according to general guidelines of ET treatment should receive IFNa which seems to be the safest option for all patients while trying conceiving. Treatment with peg-IFN is more attractive due to the longer half-life and the similar efficacy in controlling platelet count; nevertheless, there is limited data concerning safety profile [18,29,36].…”

Section: Discussionmentioning

confidence: 99%

Patients with essential thrombocytosis during pregnancy: Challenges and therapeutic dilemmas

Kanellopoulou¹

2017

Obstet Gynecol Rep

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Treatment of patients with essential thrombocytosis during pregnancy is challenging and young women are reported to be at increased risk of first trimester abortions and other pregnancy complications. In literature, there are case reports and small case series where the treatment approach differs and the results are conflicting. The addition of low dose aspirin seems to be beneficial in most cases improving pregnancy outcome whereas interferon-a is the cytoreductive drug of choice when platelet control is needed during pregnancy. Anticoagulation with low-molecular weight heparin is not generally recommended and should be considered during the last few weeks of pregnancy and postpartum.

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“…in those < 40 years of age). [14][15][16][17] In addition, IFNα reduces the allele burden in JAK2 V617F-positive patients and may induce a response that persists even after discontinuation of treatment. However, the toxicity associated with IFNα treatment should always be considered.…”

Section: Discussionmentioning

confidence: 99%