Claire N Harrison

Guy's and St Thomas' NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (156)1232.53 Total impact

  • Mary F McMullin · Bridget S Wilkins · Claire N Harrison ·
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    ABSTRACT: Polycythaemia vera (PV) is a chronic blood cancer; its clinical features are dominated by myeloproliferation (erythrocytosis, often leucocytosis and/or thrombocytosis) and a tendency for thrombosis and transformation to myelofibrosis or acute myeloid leukaemia. In the past 10 years the pathophysiology of this condition has been defined as JAK/STAT pathway activation, almost always due to mutations in JAK2 exons 12 or 14 (JAK2 V617F). In the same time period our understanding of the optimal management of PV has expanded, most recently culminating in the approval of JAK inhibitors for the treatment of PV patients who are resistant or intolerant to therapy with hydroxycarbamide. It has also been demonstrated that life expectancy for many patients with PV is not normal, nor is their quality of life. We critically explore these findings and discuss their impact. In addition, we highlight persisting gaps in our current management strategy; for example, what is the optimal first line cytoreductive therapy and, indeed, which patients need cytoreductive drugs.
    British Journal of Haematology 10/2015; DOI:10.1111/bjh.13812 · 4.71 Impact Factor
  • Yan Beauverd · Donal P McLornan · Claire N Harrison ·
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    ABSTRACT: Introduction: Myelofibrosis (MF) is a clonal haematological disease associated with recurrent somatic gene mutations (JAK2V617F, MPL, CALR) and constitutive activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription pathway. MF is often characterised by debilitating symptoms and JAK inhibitors (JAKIs) have revolutionised available therapeutic options. Ruxolitinib, a JAK1 and 2 inhibitor, is the only currently approved agent. Several other JAKIs are undergoing evaluation in the clinical trial setting and Pacritinib, a novel JAK2 and FLT3 inhibitor, is at an advanced stage of investigation with recent completion of a Phase III trial and another ongoing.Areas covered: Within this article we focus on pacritinib, summarising the development, preclinical and up-to-date results from the Phase I - III trials. We present the most recent data on efficacy and safety and indirectly compare this novel JAKI with ruxolitinib.Expert opinion: The kinome array data for pacritinib suggests that it has a range of targets differing to those for ruxolitinib. Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. It is also an attractive drug for potential combination studies due to its good tolerability.
    Expert Opinion on Pharmacotherapy 10/2015; 16(15):2381-2390. DOI:10.1517/14656566.2015.1088831 · 3.53 Impact Factor
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    ABSTRACT: Background: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan. Results: Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration. Conclusions: Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted ( identifier, NCT00934544; July 6, 2009).
    09/2015; 4(1):26. DOI:10.1186/s40164-015-0021-2
  • Donal P McLornan · Alesia A Khan · Claire N Harrison ·
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    ABSTRACT: Over the last decade, unparalleled advances have been made within the field of 'Philadelphia chromosome'-negative myeloproliferative neoplasms (MPN) regarding both disease pathogenesis and therapeutic targeting. The discovery of deregulated JAK-STAT signalling in MPN led to the rapid development of JAK inhibitor agents, targeting both mutated and wild-type JAK, which have significantly altered the therapeutic paradigm for patients with MPN. Although the largest population treated with these agents incorporates those with myelofibrosis, increasing data supports potential usage in other MPNs such as essential thromocythaemia and polycythaemia vera. Many MPNs are associated with a hyperinflammatory state and deregulation of immune homeostasis. Over the last few years, research has focused on attempting to decipher the complex and context-dependent changes that contribute to this immune deregulation. Moreover, very recent studies have demonstrated significant JAK inhibitor-mediated effects within the T cell, natural killer cell and dendritic cell compartments following exposure to JAK inhibitors. In parallel, case reports of infections occurring following exposure to ruxolitinib, many of which are atypical, have focused research efforts on delineating JAK inhibitor-associated immunological consequences. Within this review article, we will describe what is currently known about MPN-associated immune deregulation and JAK inhibitor-mediated immunomodulation.
    Current Hematologic Malignancy Reports 08/2015; DOI:10.1007/s11899-015-0284-z · 2.20 Impact Factor
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    ABSTRACT: The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet (ELN) and European Blood and Marrow Transplantation Group (EBMT). Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age less than 70 years should be considered candidates for allo-SCT. Patients with intermediate-1-risk disease and age less than 65 years should be considered candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood greater than 2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an HLA matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. Peripheral blood was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted.Leukemia accepted article preview online, 21 August 2015. doi:10.1038/leu.2015.233.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2015; 29(11). DOI:10.1038/leu.2015.233 · 10.43 Impact Factor
  • Samah Alimam · Donal McLornan · Claire Harrison ·
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    ABSTRACT: Myelofibrosis is a heterogeneous disorder, which, although sometimes asymptomatic in the early stages, is frequently associated with debilitating constitutional symptoms, poor quality of life and high degree of morbidity as the disease progresses. Ruxolitinib, a JAK1/2-inhibitor, has transformed the management of many patients by reducing disease-related symptoms and splenomegaly in intermediate-2 and high-risk patients. As demonstrated by the COMFORT studies, unprecedented clinical benefit can be gained by some patients on ruxolitinib; however, this is not without potential adverse effects, notably cytopenias, weight-gain and an increased risk of opportunistic infections. No other JAK inhibitors are currently approved for myelofibrosis. Moreover, long-term effects of JAK-inhibitor agents, such as ruxolitinib, remain unknown. Consequently, the use of ruxolitinib in the low-risk patient, in the absence of high symptom burden remains controversial and requires further randomized clinical trials. In such patients, an individualized approach should be adopted, balancing likely clinical benefit with the potential side-effect profile.
    Expert Review of Hematology 08/2015; 8(5):1-3. DOI:10.1586/17474086.2015.1074858 · 2.07 Impact Factor
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    Annals of Oncology 08/2015; 26 Suppl 5. DOI:10.1093/annonc/mdv203 · 7.04 Impact Factor
  • Samah Alimam · Bridget S. Wilkins · Claire N. Harrison ·
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    ABSTRACT: The approach to the diagnosis and management of essential thrombocythaemia (ET) is steadily changing, influenced by advances in molecular biology, data from clinical trials and retrospective analyses of patient cohorts. In the past decade options for clinical management largely remain unchanged, but who we treat, and with what target in mind, is evolving. A further area of change is recognition of symptoms that may be associated with ET, as well as other myeloproliferative neoplasms, and that potential options for their management are becoming available. Judicious and careful diagnosis is increasingly a fundamental key to successful management followed by cytoreductive therapy in a subset of patients. In this review we demonstrate our management strategies for ET using a case-based format.
    British Journal of Haematology 08/2015; 171(3). DOI:10.1111/bjh.13605 · 4.71 Impact Factor
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    ABSTRACT: Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. Fedratinib, a JAK2-selective inhibitor, previously demonstrated clinically beneficial activity in patients with MF in early-phase trials. To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF. Double-blind, randomized, placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients (≥18 years of age) with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF were randomly assigned between December 2011 and September 2012 to once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. The primary end point was spleen response (≥35% reduction in spleen volume from baseline as determined by magnetic resonance imaging or computed tomography) at week 24 and confirmed 4 weeks later. The main secondary end point was symptom response (≥50% reduction in total symptom score, assessed using the modified Myelofibrosis Symptom Assessment Form). The primary end point was achieved by 35 of 96 (36% [95% CI, 27%-46%]) and 39 of 97 (40% [95% CI, 30%-50%]) patients in the fedratinib 400-mg and 500-mg groups, vs 1 of 96 (1% [95% CI, 0%-3%]) in the placebo group (P < .001). Symptom response rates at week 24 were 33 of 91 (36% [95% CI, 26%-46%]), 31 of 91 (34% [95% CI, 24%-44%]), and 6 of 85 (7% [95% CI, 2%-13%]) in the fedratinib 400-mg, 500-mg, and placebo groups, respectively (P < .001). Common adverse events with fedratinib treatment were anemia, gastrointestinal symptoms, and increased levels of liver transaminases, serum creatinine, and pancreatic enzymes. Encephalopathy was reported in 4 women who received fedratinib 500 mg/d. A diagnosis of Wernicke encephalopathy was supported by magnetic resonance imaging in 3 cases and suspected clinically in 1 case. Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued. identifier: NCT01437787.
    06/2015; 1(5). DOI:10.1001/jamaoncol.2015.1590
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    Haematologica 06/2015; 100(9). DOI:10.3324/haematol.2015.128918 · 5.81 Impact Factor
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    ABSTRACT: CD4(+) T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN), suggesting that T cells play an important role in their pathogenesis. Treatment with JAK inhibitors (JAKi) results in improvements in MPN-associated constitutional symptoms as well as reductions in splenomegaly. However, effects of JAKi on T cells in MPN are not well established and the baseline immune signature remains unclear. We investigated the frequency and function of CD4(+) T cell subsets in 50 MPN patients at baseline as well as during treatment with either ruxolitinib or fedratinib in a subset. We show that CD4(+) CD127(low) CD25(high) FOXP3(+) T regulatory cells are reduced in MPN patients compared to healthy controls and that this decrease is even more pronounced following JAKi therapy. Moreover, we show that after 6 months of treatment the number of T helper (Th)-17 cells increased. We also describe a functional 'silencing' of T helper cells both in vivo and in vitro and a blockade of pro-inflammatory cytokines from these cells. This profound effect of JAKi on T cell function may underlay augmented rates of atypical infections that have been reported with use of these drugs. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 06/2015; DOI:10.1111/bjh.13519 · 4.71 Impact Factor
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    ABSTRACT: Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase 3 COMFORT studies. Additionally, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median 3 years of follow-up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy (hazard ratio=0.65; 95% confidence interval, 0.46-0.90; P=.01); the crossover-corrected hazard ratio was 0.29 (95% confidence interval, 0.13-0.63). Both patients with intermediate-2 or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. ( identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544). Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 06/2015; 100(9). DOI:10.3324/haematol.2014.119545 · 5.81 Impact Factor
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    ABSTRACT: The present report focuses on management strategies for the myeloproliferative neoplasm according to the structure and processes we use within our center, a large tertiary unit in central London. The standard procedures for achieving an accurate diagnosis and risk stratification and therapeutic strategies for these diseases with a detailed focus on contentious areas are discussed. In the 9 years after the description of the Janus kinase 2 mutation, this field has altered quite radically in several aspects. For example, a new therapeutic paradigm exists, especially for myelofibrosis. We share how our unit has adapted to these changes. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical lymphoma, myeloma & leukemia 06/2015; 15S:S19-S26. DOI:10.1016/j.clml.2015.02.032 · 2.02 Impact Factor
  • Alesia A Khan · Claire N Harrison · Donal P McLornan ·
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    ABSTRACT: Deregulated Hedgehog (Hh) signalling activity may be associated with a broad range of cancer types and hence has become an attractive target for therapeutic intervention. Although initial haematological interest focused on the therapeutic targeting of this pathway in chronic myeloid leukaemia), small molecule inhibitors targeting the Hh pathway are now being tested in a range of other myeloid disorders, including myelofibrosis, myelodysplasia and acute myeloid leukaemia. In this review we will evaluate the rationale for targeting of the Hh pathway in myeloid diseases and discuss the novel agents that have entered the clinical arena. We will discuss pre-clinical models, emerging clinical trial data, and suggest how these targeted therapies may address current unmet medical needs. Finally, we will explore potential limitations of these therapies due to the emergence of secondary resistance mechanisms and speculate on future developments within this arena. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 04/2015; 170(3). DOI:10.1111/bjh.13426 · 4.71 Impact Factor
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    ABSTRACT: Myelofibrosis (MF), including primary, post-essential thrombocythemia and post-polycythemia vera MF, associates with a reduced quality of life and shortened life expectancy. Dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is prominent, even in the absence of the JAK2(V617F) mutation. Therefore, all symptomatic MF patients may potentially derive benefit from JAK inhibitors. Despite the efficacy of JAK inhibitors in controlling signs and symptoms of MF, they do not eradicate the disease. Therefore, JAK inhibitors are currently being tested in combination with other novel therapies, a strategy which may be more effective in reducing disease burden, either by overcoming JAK inhibitor resistance or targeting additional mechanisms of pathogenesis. Additional targets include modulators of epigenetic regulation, pathways that work downstream from JAK/STAT (i.e., mammalian target of rapamycin/AKT/phosphoinositide 3-kinase,) heat shock protein 90, hedgehog signaling, pro-fibrotic factors, abnormal megakaryocytes and telomerase. In this review, we discuss novel MF therapeutic strategies.
    Leukemia & lymphoma 04/2015; 56(10):1-30. DOI:10.3109/10428194.2015.1037762 · 2.89 Impact Factor
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    ABSTRACT: Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2(V617F)-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10(-10)) and rs2201862 (MECOM; meta-analysis P=1.96 × 10(-9)). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2(V617F)-positive cases. rs9376092 has a stronger effect in JAK2(V617F)-negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5 × 10(-7)), whereas in JAK2(V617F)-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ(2) P=7.3 × 10(-7)). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype.
    Nature Communications 04/2015; 2015(6):6691. DOI:10.1038/ncomms7691 · 11.47 Impact Factor
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    Claire Harrison ·

    Haematologica 04/2015; 100(4):409-11. DOI:10.3324/haematol.2015.124099 · 5.81 Impact Factor
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    ABSTRACT: Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The primary composite endpoint was the proportion of patients achieving treatment success [≥50% reduction in palpable spleen length and/or a ≥50% decrease in Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF TSS)] at 48 weeks. This was the first time that efficacy of ruxolitinib in myelofibrosis has been evaluated based on these criteria and the first time the MF-SAF was used in a population of patients solely from the United Kingdom. Overall, 50% of patients and 57% of intermediate-1 risk patients, achieved treatment success; reductions in spleen length and symptoms were observed in all risk groups. The majority of patients (66·7%) experienced ≥50% reductions from baseline in spleen length at any time. Improvements in MF-SAF TSS were seen in 80·0%, 72·7%, and 72·2% of intermediate-1, intermediate-2, and high-risk patients, respectively. Consistent with other studies of ruxolitinib, the most common haematological adverse events were anaemia and thrombocytopenia. Results indicate that most patients with myelofibrosis, including intermediate-1 risk patients, may benefit from ruxolitinib treatment. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 03/2015; 170(1). DOI:10.1111/bjh.13379 · 4.71 Impact Factor
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    ABSTRACT: Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which mutations are acquired. We determined mutation order in patients with myeloproliferative neoplasms by genotyping hematopoietic colonies or by means of next-generation sequencing. Stem cells and progenitor cells were isolated to study the effect of mutation order on mature and immature hematopoietic cells. The age at which a patient presented with a myeloproliferative neoplasm, acquisition of JAK2 V617F homozygosity, and the balance of immature progenitors were all influenced by mutation order. As compared with patients in whom the TET2 mutation was acquired first (hereafter referred to as "TET2-first patients"), patients in whom the Janus kinase 2 (JAK2) mutation was acquired first ("JAK2-first patients") had a greater likelihood of presenting with polycythemia vera than with essential thrombocythemia, an increased risk of thrombosis, and an increased sensitivity of JAK2-mutant progenitors to ruxolitinib in vitro. Mutation order influenced the proliferative response to JAK2 V617F and the capacity of double-mutant hematopoietic cells and progenitor cells to generate colony-forming cells. Moreover, the hematopoietic stem-and-progenitor-cell compartment was dominated by TET2 single-mutant cells in TET2-first patients but by JAK2-TET2 double-mutant cells in JAK2-first patients. Prior mutation of TET2 altered the transcriptional consequences of JAK2 V617F in a cell-intrinsic manner and prevented JAK2 V617F from up-regulating genes associated with proliferation. The order in which JAK2 and TET2 mutations were acquired influenced clinical features, the response to targeted therapy, the biology of stem and progenitor cells, and clonal evolution in patients with myeloproliferative neoplasms. (Funded by Leukemia and Lymphoma Research and others.).
    New England Journal of Medicine 02/2015; 372(7):601-12. DOI:10.1056/NEJMoa1412098 · 55.87 Impact Factor
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    ABSTRACT: Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard-therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy. In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera. (Funded by Incyte and others; RESPONSE number, NCT01243944.).
    New England Journal of Medicine 01/2015; 372(5):426-35. DOI:10.1056/NEJMoa1409002 · 55.87 Impact Factor

Publication Stats

6k Citations
1,232.53 Total Impact Points


  • 2005-2015
    • Guy's and St Thomas' NHS Foundation Trust
      • Department of Haematology
      Londinium, England, United Kingdom
  • 2012
    • Wellcome Trust Sanger Institute
      • Cancer Genome Project
      Cambridge, ENG, United Kingdom
  • 2011
    • Rosalind Franklin University of Medicine and Science
      North Chicago, Illinois, United States
  • 2009
    • Cambridge Institute for Medical Research
      • Department of Haematology
      Cambridge, England, United Kingdom
  • 2005-2009
    • University of Cambridge
      • Department of Haematology
      Cambridge, ENG, United Kingdom
  • 1998-2009
    • University of Birmingham
      • Birmingham Clinical Trials Unit
      Birmingham, England, United Kingdom
  • 2007
    • Belfast Healthy Cities
      Béal Feirste, N Ireland, United Kingdom
  • 2006
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1998-2001
    • University College London
      • Department of Haematology
      Londinium, England, United Kingdom