Interferon‐alpha‐induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis

Chott, Andreas; Gisslinger, Heinz; Thiele, Jüergen; Fritz, Elke; Linkesch, Werner; Radaszkiewicz, T; Ludwig, Heinz

doi:10.1111/j.1365-2141.1990.00001.x-i1

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…Common side effects of PEG-IFNα-2a+RBV therapy include anaemia, leucopoenia and thrombocytopenia (17)(18)(19). Ribavirin has haemolytic effects and often causes anaemia, whereas IFNα has been shown to suppress haematopoietic progenitor cells in the bone marrow to induce leucopoenia and thrombocytopenia (20)(21)(22). Likewise, our study showed a statistically significant decrease in Hgb levels and RBC, Pt, WBC and Ne counts (p<0,001).…”

Section: Discussionsupporting

confidence: 70%

Hepatitis C Therapy – Related Haematological Side Effects are Associated with Treatment Outcome / Hematološka Neželjena Dejstva Terapije Hepatitisa C Su Povezana Sa Ishodom Lecenja

Vuković

Baskić

Mijailović

et al. 2016

Serbian Journal of Experimental and Clinical Research

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Treatment of patients suff ering from chronic hepatitis C with standard pegylated interferon alpha 2a plus ribavirin has limited effi cacy. erapy outcome is dependent on several factors of both the host and virus, including age, sex, stage of fi brosis, viral genotype, viral load, and occurrence of haematological adverse events during chronic hepatitis C treatment. e aim of this study was to determine the relationship between the viral and host factors and the haematological side eff ects of therapy with sustained virological response.Fifty-four patients were treated with combined pegylated interferon alpha 2a plus ribavirin therapy. Hepatitis C virus genotyping, viral load, histopathological liver changes and biochemical parameters were evaluated for each patient before beginning treatment. Each patient's blood count was analysed during each clinical visit.Sustained virological response was achieved in 75,9% of patients. Baseline AST and ALT levels were signifi cantly higher in patients with a poor response to therapy (p<0,05). Other clinical and laboratory parameters did not reach statistical signifi cance. Both responders and non-responders developed anaemia. A decrease in thrombocytes, neutrophils and white blood cells was signifi cantly associated with a sustained response to therapy (p<0,05, p<0,05 and p<0,001, respectively).Sustained virological response was associated with lower baseline AST and ALT values and thrombocytopenia, leucopenia and neutropenia at the end of the treatment. All treated patients developed anaemia.

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Section: Discussionsupporting

confidence: 70%

Hepatitis C Therapy – Related Haematological Side Effects are Associated with Treatment Outcome / Hematološka Neželjena Dejstva Terapije Hepatitisa C Su Povezana Sa Ishodom Lecenja

Vuković

Baskić

Mijailović

et al. 2016

Serbian Journal of Experimental and Clinical Research

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“…These observations suggests that IFN-a can change the PV disease course to the preproliferative phase [37]. IFN-a has also been shown to decrease the levels of cytokines such as platelet-derived growth factor, transforming growth factor-b, and others that play a role in the development and clinical symptomology of MPNs [38].…”

Section: Interferonmentioning

confidence: 92%

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

Nazha

Gerds

2016

The Oncologist

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The goals of therapy in patients with polycythemia vera (PV) are to improve disease‐related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first‐line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6‐fold increase in mortality and a 6.8‐fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon‐α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation. Implications for Practice: The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration‐approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low‐dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies.

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“…Although, as noted, PV is a clonal stem cell disorder; there have been case reports of the resumption of polyclonal hematopoiesis after rIFN-a therapy (C. Steimle et al, manuscript submitted for publication). 24,25 rIFN-a inhibits erythroid progenitors and erythroid burst-forming units in vitro, 26 and produces morphologic and biochemical changes in megakaryocytes, 27 including a decrease in megakaryocyte density, size, and proliferation. IFN inhibits megakaryocyte progenitor proliferation and reduces thrombopoietin-induced Mpl receptor signaling.…”

Section: Myelosuppressive Therapymentioning

confidence: 99%

Treatment of Polycythemia Vera

Silver

2006

Semin Thromb Hemost

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The selection of treatment for patients with polycythemia vera (PV) still is the subject of much discussion among hematologists. It is emphasized that important physiologic and pathogenic components of the illness relate not only to the erythroid cell, but also to the megakaryocyte. Both play essential roles in causing complications of the disease. Hematologists agree that the mainstay in treatment remains phlebotomy, a basic pillar of the concept of PRIMUM NON NOCERE. In general, the target levels for the hematocrit have been accepted as

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Interferon‐alpha‐induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis

Cited by 8 publications

References 23 publications

Hepatitis C Therapy – Related Haematological Side Effects are Associated with Treatment Outcome / Hematološka Neželjena Dejstva Terapije Hepatitisa C Su Povezana Sa Ishodom Lecenja

Hepatitis C Therapy – Related Haematological Side Effects are Associated with Treatment Outcome / Hematološka Neželjena Dejstva Terapije Hepatitisa C Su Povezana Sa Ishodom Lecenja

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

Treatment of Polycythemia Vera

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