The burden of fatigue and quality of life in myeloproliferative disorders (MPDs)

Mesa, Ruben A.; Niblack, Joyce; Wadleigh, Martha; Verstovšek, Srđan; Camoriano, John; Barnes, Sunni A.; Tan, Angelina D.; Atherton, Philip J.; Sloan, Jeff A.; Tefferi, Ayalew

doi:10.1002/cncr.22365

Cited by 347 publications

(265 citation statements)

References 48 publications

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“…Loss of body weight and drenching night sweats profoundly affect quality of life. 38 The clinical relevance of constitutional symptoms is underlined by their inclusion as an adverse prognostic risk factor in the IPSS. A specific instrument, the Myeloproliferative Neoplasm Symptom Assessment Form, has been developed to quantitatively assess symptomatic burden, and represents a major advance for rigorously addressing the impact of these manifestations on the patients' quality of life and for objectively measuring the response to conventional and novel therapies.…”

Section: Constitutional Symptomsmentioning

confidence: 99%

Management of Myelofibrosis

Vannucchi

2011

Hematology

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Myelofibrosis (MF), either primary or arising from previous polycythemia vera (PV) or essential thrombocythemia (ET), is the worst among the chronic myeloproliferative neoplasms in terms of survival and quality of life. Patients with MF have to face several clinical issues that, because of the poor effectiveness of medical therapy, surgery or radiotherapy, represent largely unmet clinical needs. Powerful risk stratification systems, applicable either at diagnosis using the International Prognostic Scoring System (IPSS) or during the variable course of illness using the Dynamic International Prognostic Scoring System (DIPSS) and DIPSS Plus, allow recognition of categories of patients with survival times ranging from decades to Ͻ 2 years. These scores are especially important for therapeutic decisions that include allogeneic stem cell transplantation (allogeneic SCT), the only curative approach that still carries a nonnegligible risk of morbidity and mortality even with newest reduced intensity conditioning (RIC) regimens. Discovery of JAK2V617F mutation prompted the development of clinical trials using JAK2 inhibitors; these agents overall have resulted in meaningful symptomatic improvement and reduction of splenomegaly that were otherwise not achievable with conventional therapy. Intriguing differences in the efficacy and tolerability of JAK2 inhibitors are being recognized, which could lead to a nonoverlapping spectrum of activity/safety. Other agents that do not directly target JAK2 and have shown symptomatic efficacy in MF are represented by inhibitors of the mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). Pomalidomide appears to be particularly active against MF-associated anemia. However, because these agents are all poorly effective in reducing the burden of mutated cells, further advancements are needed to move from enhancing our ability to palliate the disease to arriving at an actual cure for MF.

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Section: Constitutional Symptomsmentioning

confidence: 99%

Management of Myelofibrosis

Vannucchi

2011

Hematology

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“…Previous studies of MPN-related fatigue indicate that it occurs in 81% 2 to 95% 3 of patients with MPNs and is the predominant symptom regardless of MPN subtype. [2][3][4][5][6][7] This fatigue reduces both physical and social functioning and substantially impairs quality of life. 2 Fatigue is a particular challenge for clinicians and patients due to its multifactorial nature.…”

Section: Introductionmentioning

confidence: 99%

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms

Scherber

Kosiorek

Senyak

et al. 2015

Cancer

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BACKGROUND Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODS A 70‐item, Internet‐based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTS Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P = .006), diabetes mellitus (P = .045), fibromyalgia (P < 0.001), chronic fatigue syndrome (P = .006), and chronic kidney disease (P = .02). Current use of antidepressants (P<.001), antihistamines (P = .0276), antianxiety medications (P = .0357), and prescription pain medications (P<.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001). CONCLUSIONS The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain. Cancer 2016;122:477–485. © 2015 American Cancer Society.

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“…However, elevated serum inflammatory cytokine levels have been reported in MPN patients (Barbui et al , 2011; Vaidya et al , 2012; Pourcelot et al , 2014) and may contribute to the severity of symptoms, including itching and night sweats (Tefferi et al , 2011; Squires et al , 2013). Other common aspects of the PV disease state, including blood hyperviscosity (Barbui et al , 2013) and splenomegaly (Mesa et al , 2007), may also play a role in the symptom profile of some patients. The overall PV‐related symptom burden, as measured by the MPN Symptom Assessment Form total symptom score (MPN‐SAF TSS), as well as the severity of individual symptoms, including fatigue (Emanuel et al , 2012; Abelsson et al , 2013) and itching (Siegel et al , 2013), have been associated with reduced quality of life in patients with PV.…”

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confidence: 99%

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

et al. 2016

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SummaryThe randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV‐related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster (TSS‐C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib‐ and hydroxycarbamide‐treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82–4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS‐C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV‐related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.

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The burden of fatigue and quality of life in myeloproliferative disorders (MPDs)

Cited by 347 publications

References 48 publications

Management of Myelofibrosis

Management of Myelofibrosis

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

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