Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response

Pizzi, Marco; Silver, Richard T.; Barel, Ariella; Orazi, Attilio

doi:10.1038/modpathol.2015.93

Cited by 49 publications

(30 citation statements)

References 34 publications

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“…In early stages of the disease, there are some data from case-series to support the use of IFNa. 27,28 HC is recommended for control of leukocytosis, thrombocytosis, and splenomegaly, although data from controlled studies are lacking; effect on symptoms is minimal and was no different from placebo in the COMFORT studies. 29 Splenectomy may be indicated for selected patients with symptomatic, treatment-resistant splenomegaly; for transfusion-dependent anemia; or for symptomatic portal hypertension when balanced against risks; that is, 5% to 10% mortality and 30% to 40% risks for thrombosis, bleeding, or infection.…”

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confidence: 99%

Emerging treatments for classical myeloproliferative neoplasms

Vannucchi

Harrison

2017

Blood

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There has been a major revolution in the management of patients with myeloproliferative neoplasms (MPN), and in particular those with myelofibrosis and extensive splenomegaly and symptomatic burden, after the introduction of the JAK1 and JAK2 inhibitor ruxolitinib. The drug also has been approved as second-line therapy for polycythemia vera (PV). However, the therapeutic armamentarium for MPN is still largely inadequate for coping with patients’ major unmet needs, which include normalization of life span (myelofibrosis and some patients with PV), reduction of cardiovascular complications (mainly PV and essential thrombocythemia), prevention of hematological progression, and improved quality of life (all MPN). In fact, none of the available drugs has shown clear evidence of disease-modifying activity, even if some patients treated with interferon and ruxolitinib showed reduction of mutated allele burden, and ruxolitinib might extend survival of patients with higher-risk myelofibrosis. Raised awareness of the molecular abnormalities and cellular pathways involved in the pathogenesis of MPN is facilitating the development of clinical trials with novel target drugs, either alone or in combination with ruxolitinib. Although for most of these molecules a convincing preclinical rationale was provided, the results of early phase 1 and 2 clinical trials have been quite disappointing to date, and toxicities sometimes have been limiting. In this review, we critically illustrate the current landscape of novel therapies that are under evaluation for patients with MPN on the basis of current guidelines, patient risk stratification criteria, and previous experience, looking ahead to the chance of a cure for these disorders.

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confidence: 99%

Emerging treatments for classical myeloproliferative neoplasms

Vannucchi

Harrison

2017

Blood

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“…Outside a clinical trial setting, there is no standard approach to follow‐up histological assessment. At the discretion of the treating haematologist and the patient, a repeat marrow examination could be considered after several years of haematological response, particularly in patients with MF where successful clinical response correlates with an improvement in bone marrow morphology (reduction in marrow fibrosis, cellularity and megakaryocyte density) . Measuring molecular response by the allele burden of JAK2 V617F (or other mutations) is not currently standard practice in Australia.…”

Section: Monitoring Response To Treatmentmentioning

confidence: 99%

“…At the discretion of the treating haematologist and the patient, a repeat marrow examination could be considered after several years of haematological response, particularly in patients with MF where successful clinical response correlates with an improvement in bone marrow morphology (reduction in marrow fibrosis, cellularity and megakaryocyte density). 36 Measuring molecular response by the allele burden of JAK2 V617F (or other mutations) is not currently standard practice in Australia. Complete response from a molecular viewpoint is defined as eradication of the preexisting abnormality and a partial response as ≥50% decrease in allele burden.…”

Section: Dosing and Administration Of Peg-ifnmentioning

confidence: 99%

Recommendations for the use of pegylated interferon‐α in the treatment of classical myeloproliferative neoplasms

Forsyth

Chan

Grigg

et al. 2019

Internal Medicine Journal

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The classical myeloproliferative neoplasms (MPN) are uncommon clonal haemopoietic malignancies characterised by excessive production of mature blood cells. Clinically, they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon‐α (IFN), but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side‐effects. The pegylated form of IFN is a long‐acting preparation, which is better tolerated, and its Pharmaceutical Benefits Scheme listing is likely to lead to increased usage. We review the literature on risks and benefits of IFN treatment for MPN, suggest criteria for patient selection in each of these diseases and discuss strategies to manage the side‐effects of pegylated IFN.

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“…Previous studies indicated that recombinant interferon-α has the potential to decrease the proliferation of PMF neoplastic stem cells with a significant reduction of marrow fibrosis, cellularity and megakaryocyte density,55, 56 which can result in improvements of splenomegaly and blood counts 56, 57. Systemic toxicity (cytopenias, asthenia, fatigue, myalgia) may limit interferon use in a proportion of patients; however, most cases can be manageable with dose reductions 55, 56. Larger studies are necessary to fully support interferon use in PMF patients and its effects on overall survival.…”

Section: Treatment Optionsmentioning

confidence: 99%

Primary myelofibrosis: current therapeutic options

Campos

2016

Revista Brasileira de Hematologia e Hemoterapia

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Primary myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm characterized by clonal myeloid expansion, followed by progressive fibrous connective tissue deposition in the bone marrow, resulting in bone marrow failure. Clonal evolution can also occur, with an increased risk of transformation to acute myeloid leukemia. In addition, disabling constitutional symptoms secondary to the high circulating levels of proinflammatory cytokines and hepatosplenomegaly frequently impair quality of life. Herein the main current treatment options for primary myelofibrosis patients are discussed, contemplating disease-modifying therapeutics in addition to palliative measures, in an individualized patient-based approach.

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Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response

Cited by 49 publications

References 34 publications

Emerging treatments for classical myeloproliferative neoplasms

Emerging treatments for classical myeloproliferative neoplasms

Recommendations for the use of pegylated interferon‐α in the treatment of classical myeloproliferative neoplasms

Primary myelofibrosis: current therapeutic options

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