Pregnancy and its management in the Philadelphia negative myeloproliferative diseases

Harrison, Claire

doi:10.1111/j.1365-2141.2005.05400.x

Cited by 109 publications

(107 citation statements)

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“…81,82 Indeed, when cytoreduction is necessary during pregnancy, many publications have documented the safety of IFN-a in MPN mothers as well as fetuses. 98,99 However, there are very limited data available on the long-term safety of IFN-a in children exposed to this drug during pregnancy. Recent results, however, suggest that indications of treatment with IFN-a should be larger.…”

Section: Discussionmentioning

confidence: 99%

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

2008

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Interferon (IFN) was the first cytokine discovered 50 years ago, with a wide range of biological properties, including immunomodulatory, proapoptotic and antiangiogenic activities, that rapidly raised interest in its therapeutic use in malignancies. IFN-receptor characterization was also pivotal in the discovery of the JAK/STAT signaling pathway. Among the large IFN family, mainly one of the type I IFN, IFN-a2, is used in therapy. Many clinical trials have shown remarkable efficacy of IFN-a in bcr-abl-negative myeloproliferative neoplasms (MPNs), especially polycythemia vera (PV), and essential thrombocythemia (ET). IFN-a induces about 80% of hematological responses in those diseases and is able to reduce splenomegaly, as well as relieve pruritus and other constitutional symptoms. Yet its use was limited by toxicity, leading to early treatment discontinuation in about 20% of the patients. However, its lack of leukemogenic potential and its possible use during pregnancy have already made IFN-a the drug of choice for younger MPN patients. In addition, several studies have shown a probably selective effect of IFN-a on PV and ET clones, as shown by cytogenetic remissions, reversions to polyclonal hematopoiesis, and more recently by induction of JAK2V617F complete molecular remissions in PV which may widen the indications of IFN-a in JAK2-mutated MPN.

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Section: Discussionmentioning

confidence: 99%

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

2008

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“…21,22 Concerning contraception, there is currently insufficient evidence either to support or refute an association between estrogen-based hormonal treatment and thrombosis in MPNs. 23 My suggestion is to avoid the use of estrogen-based contraceptives in MPNs and to use alternative methods.…”

Section: How To Diagnose Mpn In Children and Young Adultsmentioning

confidence: 99%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

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On the basis of my personal clinical and research experience and validated by the current literature, my approach to the management of pediatric (age o18 years) and young patients (age o40 years) with classic myeloproliferative neoplasms is presented by focusing on diagnosis, patient communication, risk stratification and therapy. The WHO-2008 diagnostic criteria are recommended, even though in children suspected with essential thrombocythemia (ET), a specific set of diagnostic features may be required. Patient communication includes information on natural history, genetic abnormalities and counseling in all women of child-bearing age. The main challenge in children and young adults with ET and polycythemia vera (PV) is to avoid recurrence of major thrombosis by selecting those patients who ultimately can benefit from cytotoxic and antithrombotic therapy without increasing the incidence of drug-induced side effects. In asymptomatic low-risk patients no therapy is prescribed while in high-risk low-dose aspirin, hydroxyurea and interferon-alpha are my first line drugs. My first decision when considering treatment of a young patient with primary myelofibrosis (PMF) or post-PV or post ET-myelofibrosis, is whether he/she qualifies for bone marrow allotransplantation. In the remaining young PMF patients palliative therapy or experimental drugs are considered.Leukemia ( Keywords: myeloproliferative neoplasms; treatment; young people INTRODUCTION Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are currently classified among the bcr/abl-negative, 'classic' myeloproliferative neoplasms (MPNs) and represent a stem cell-derived clonal myeloproliferation. Hematopoietic progenitors derived from patients with MPNs are hypersensitive to the stimulation of physiological growth factors such as thrombopoietin or erythropoietin (EPO). 1 Since 2005, the pathophysiology of these diseases has advanced considerably with the discovery of an acquired mutation of JAK2 V617F in a vast majority of PV patients and in almost half of those with ET and PMF. 2 The mutation, located within the negative regulatory pseudokinase, or Janus homology 2 domain, causes cytokine-independent activation of several biochemical pathways implicated in EPO receptor signaling. Subsequently, mutations in MPL were reported in B4% of patients with ET or PMF. The significance of JAK2 and MPL mutations for the evolution of the MPNs and their relative roles in determining disease phenotype as well as progression to myelofibrosis and leukemic transformation are unclear at present.In this context, it should be underscored that most of the information in terms of diagnosis, prognosis and therapy focuses on the 'average' MPN patients of whom median age ranges between 60 and 65 years. On the other hand, less consistent data are available in the groups of MPN patients who are presenting below this median age such as pediatric and young adults (20% of MPN patients). This issue is now becoming more and more important, because with the ad...

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“…Previous studies have shown live birth rates of 50% to 70%, and spontaneous abortion rates of 25% to 50%, mostly during the first trimester. 73 The pathogenesis of these complications is unclear; age, parity, thrombophilia, PLT count, WBC count, and hemoglobin level have not been found to be predictive of pregnancy outcome in ET. [74][75][76] Whether the use of aspirin can improve pregnancy outcome is uncertain [74][75][76][77] ; however, a meta-analysis of randomized trials conducted outside ET concluded that low-dose aspirin is effective in preventing preeclampsia, being safe for both mother and fetus.…”

Section: Distinguishing Familial Et From Hereditary Thrombocytosismentioning

confidence: 99%

How I treat essential thrombocythemia

Rumi

Cazzola

2016

Blood

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Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm that may be complicated by vascular events, including both thrombosis and bleeding. This disorder may also transform into more aggressive myeloid neoplasms, in particular into myelofibrosis. The identification of somatic mutations of JAK2, CALR, or MPL, found in about 90% of patients, has considerably improved the diagnostic approach to this disorder. Genomic profiling also holds the potential to improve prognostication and, more generally, clinical decision-making because the different driver mutations are associated with distinct clinical features. Prevention of vascular events has been so far the main objective of therapy, and continues to be extremely important in the management of patients with ET. Low-dose aspirin and cytoreductive drugs can be administered to this purpose, with cytoreductive treatment being primarily given to patients at high risk of vascular complications. Currently used cytoreductive drugs include hydroxyurea, mainly used in older patients, and interferon α, primarily given to younger patients. There is a need for disease-modifying drugs that can eradicate clonal hematopoiesis and/or prevent progression to more aggressive myeloid neoplasms, especially in younger patients. In this article, we use a case-based discussion format to illustrate our approach to diagnosis and treatment of ET.

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Pregnancy and its management in the Philadelphia negative myeloproliferative diseases

Cited by 109 publications

References 98 publications

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

How to manage children and young adults with myeloproliferative neoplasms

How I treat essential thrombocythemia

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