Discrepancies in Treatment Goals and Concerns Regarding Disease Management between Patients with Myeloproliferative Neoplasms and Hematologists in China: Analysis from a Multicenter Cross-Sectional Survey

Cytokine profiles in polycythemia vera and essential thrombocythemia patients: Clinical implications

Gaps in Perception Between Patients and Physicians Regarding Symptomatology and Treatment Attitudes for Myeloproliferative Neoplasms: MPN LANDMARK SURVEY

Cause-specific mortality following polycythemia vera, essential thrombocythemia, and primary myelofibrosis in the US population, 2001-2017.

Background:Previous patient (pt) and physician surveys in North America, Europe and Japan have extensively documented the high symptom burden associated with myeloproliferative neoplasms (MPNs) such as myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET). No such data are available for the rest of the world.Aims:To evaluate pt‐ and physician‐reported perceptions of symptom burden, treatment goals and disease management.Methods:A cross‐sectional survey of pts with MPNs and physicians treating pts with MPNs was conducted in China, Turkey, Russia, Taiwan, South Korea and Saudi Arabia. No pt data were collected in Saudi Arabia. Independently recruited respondents completed an online survey measuring their perceptions of the impact of MPNs.Results:A total of 506 pts (MF: n = 147; PV: n = 168; ET: n = 191) completed the survey (52% female; median patient age ± SD: 60.0 ± 10.69 years). Most pts were experiencing symptoms for ≤1 year prior to MPN diagnosis (83%). A total of 240 physicians (68% hematologists, 32% hemato‐oncologists) completed the survey. At consultation, only 36% of physicians used a validated symptom assessment form; 39% used their own rating method. Many pts also did not recognize that their symptoms could be MPN‐related. For example, fatigue/tiredness was one of the most commonly reported symptoms to physicians (69% MF, 40% PV, 54% ET); however, many pts did not think their fatigue resulted from MPNs (18% MF, 25% PV, 18% ET). Consistent with this, physicians (43%) indicated that pts could only identify few/some of their symptoms as MPN‐related.A high proportion of physicians (94%) and pts (82%) felt that MPN symptoms reduce a pts’ quality of life (QoL). Furthermore, 83% of physicians reported that even mild‐moderate symptoms can have a negative impact on QoL.Despite this, while more physicians than pts ranked a better QoL as a key treatment goal, reducing MPN symptoms seemed to be a priority more commonly for pts (72% MF; 68% PV; 68% ET) than physicians (61% MF, 43% PV, 55% ET) (Figure). Slowing/delay in disease progression as a treatment goal was more common for physicians than pts in PV.As well as a high symptom prevalence, pts reported a substantial emotional burden associated with their disease: 78% MF, 59% PV and 57% ET pts were anxious/worried about their condition. Overall, a high burden on activities of daily living (ADL) was reported, especially in MF.Only 28% physicians felt in complete agreement with their pts on treatment goals. Furthermore, one quarter of pts were dissatisfied with their doctor's understanding and support of their treatment goals, and pts reported often feeling worse than their physician was aware (62% MF; 42% PV; 47% ET). Interestingly, approximately half of pts still expressed high satisfaction with their doctor's management and treatment of their MPN.Summary/Conclusion:This study revealed a lack of understanding of MPN symptoms among pts; physicians agreed that their pts could identify few MPN‐related symptoms. Although physicians acknowledge adverse impact of symptoms on QoL, more pts than physicians see reducing symptoms as a treatment goal. Despite reported pt satisfaction in disease management, pt‐ physician disconnects are apparent, demonstrating a need for improved communication. A need for standardization in symptom assessment was also highlighted, which could result in improved pt understanding of MPNs. Subtle differences from survey results in other geographies would be discussed.image

Gene expression profiling with principal component analysis depicts the biological continuum from essential thrombocythemia over polycythemia vera to myelofibrosis

Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN LANDMARK SURVEY in the United States

Gender Is a Core Modifier of Disease Outcomes and Survival in the MPN

Background: Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET), experience troublesome symptoms leading to impaired functioning (physical and psychosocial) and quality of life (QoL). Understanding symptom burden, QoL and unmet patient needs across disease subgroups is of value to aid optimal treatment and rehabilitation decision-making for patients with different MPNs. It is also worthy to explore perceptions on the impact of the disease and its treatment among MPN patients and hematologists to ensure patient-centered care. Aims: The national survey MPN-QoL-2020 was aimed to evaluate QoL and symptom burden in patients with MPN, as well as to examine the perceptions of patients and physicians about the impact of MPN and its treatment in a real world setting in Russia. Methods: A survey of patients with MPN and their treating physicians was conducted from September to December 2020. This survey included in- or out-patients aged ≥18 years with a confirmed diagnosis of MF, PV, or ET. All the patients completed the HM-PRO, a hematological malignancy (HM) specific patient-reported outcomes (PRO) measure, the MPN10 symptom assessment tool, and a patient’s survey checklist. The HM-PRO consists of two scales: Part A measuring the ‘impact on patients’ QoL’; Part B measuring ‘signs and symptoms’ experienced by the patients. Part A has 4 domains: physical behaviour (PB), social well-being (SW), emotional behaviour (EB) and eating and drinking habits (ED). Physicians completed a physician’s survey checklist which included a record for each patient. Both paper and electronic versions of the survey forms were available. ANOVA and χ2 test were applied to examine the differences between groups. Results: 1100 patients with MPNs (MF, n=355, PV, n= 408 and ET, n=337; mean age = 58±14 yrs; female = 61%) and 100 hematologists (mean age = 42±12 yrs, female = 85%) from 37 medical centers completed the survey. The HM-PRO Parts A & B total scores were significantly worse (higher scores) in MF and PV patients than in ET (Table 1). Impact on PB and EB was higher in MF and PV as compared to ET: PB = 28.6 and 21.4 vs 14.3; EB = 31.8 and 27.3 vs 22.7, respectively. Impact on ED was higher in MF as compared to PV and ET. SF was less impaired and similar across different MPNs. Among MF there were more patients with moderate/large effect on QoL as compared to PV and ET – 40% vs 34% and 28% (p=0.003). The vast majority of MPN patients experienced symptoms (95%); more than 80% had fatigue and inactivity. The MPN10 Total Symptom Score was the highest in MF, intermediate in PV and the lowest in ET: 24 vs 20 vs 14 (p<0.001). Notably, 29% MF, 34% PV and 44% ET patients did not attribute their symptoms to MPN. Physicians and patients had a discordant perspective of the most bothersome symptoms. There was agreement between MF patients and their physicians about the impact of the disease on QoL and symptom burden. For PV and ET, physicians underestimated patient’s concerns; the discrepancies were pronounced for QoL impact (PV, p=0.028; ET, p<0.001) and symptom burden (PV, p=0.018; ET, p<0.001). Across MPNs, 41.5% MF, 37.8% PV and 35.2% ET agreed that there were areas of patient-physician relationship needed to be improved. Image:Summary/Conclusion: The findings of this nationwide survey demonstrate differences in the impact on QoL and symptom burden across MPNs, identify the areas of different perspective between patients and physicians about MPN and its treatment as well as highlight the unmet needs among patients with MPN.

Thrombotic Complications in Ph'-Negative Myeloproliferative Neoplasms - 10-Year Experience of A Medical Center in Asian Area

Financial Burden of Myeloproliferative Neoplasms on Patients: Results from the MPN Landmark Survey in the United States

Health Care Utilization and Associated Costs in Elderly Persons with Non-CML Myeloproliferative Neoplasms: Real-World Evidence From a United States Medicare Population

Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray

The clinical criteria according to the Polycythemia Vera Study Group (PVSG) do not distinguish between essential thrombocythemia (ET), thrombocythemia associated with early-stage polycythemia vera (PV) and prefibrotic chronic idiopathic myelofibrosis (CIMF). The criteria only classify the advanced stage of PV with increased red cell mass. The classification of myeloproliferative disorders (MPDs), proposed by the World Health Organization (WHO) in 2001, is a compromise of the clinical PVSG and WHO bone marrow criteria, and excludes early stages of ET and PV. The updated European clinical and pathological criteria combine the WHO bone marrow criteria with established and new clinical, laboratory, biological, and molecular MPD markers. This allows clinicians and pathologists to diagnose early-stage MPD and to differentiate ET, PV, and prefibrotic chronic idiopathic myelofibrosis (CIMF). Depending on laboratory tests and diagnostic criteria used, the population of the MPD patients defined as ET, PV, and CIMF are heterogeneous at the clinical, laboratory, and biological and pathological levels. The recent discovery of the JAK2 V617F mutation, which is the cause of a distinct trilinear MPD in its manifold clinical manifestations during long-term follow-up, increases the specificity of a positive JAK2 V617F polymerase chain reaction (PCR) test for the diagnosis of MPD (near 100%), but only half of the ET and CIMF patients according to the PVSG (sensitivity 50%) and the majority of PV patients (sensitivity 95%) are JAK2 V617F positive. A comparison of the laboratory features of JAK2 V617-positive and JAK2 wild-type ET patients clearly showed that JAK2 V617-positive ET is characterized by higher values for hemoglobin, hematocrit, and neutrophil counts; lower values for serum erythropoietin (EPO) levels, serum ferritin, and mean corpuscular volume; and by increased cellularity of the bone marrow in biopsy material. This indicates that JAK2 V617-positive ET patients, diagnosed according to the PVSG criteria, represent a "forme fruste of PV" consistent with early PV mimicking ET (JAK2 V617F trilinear MPD). In contrast, the JAK2 wild-type ET patients had significantly higher platelet counts and usually had a clinical picture of ET with normal serum EPO levels, PRV-1 expression, and leukocyte alkaline phosphatase score, and a typical WHO ET bone marrow picture. The clinical and pathological data on JAK2 V617F-positive MPD patients suggest that the JAK2 V617F mutation defines one disease entity with several sequential steps of ET, PV, and secondary myelofibrosis during long-term follow-up, and that the wild-type JAK2 MPDs may represent another distinct entity with a related but different molecular etiology. MPD-specific markers such as serum EPO, endogenous erythroid colony formation (EEC), and JAK2 V617F have high specificities, but the sensitivities are not high enough to detect the early stages of the MPDs, ET, PV, and prefibrotic CIMF. Bone marrow histopathology in addition to clinical, laboratory, biological, and molecular markers, including the JAK2 V617 PCR test, serum EPO, PRV-1, EEC, LAP score, peripheral blood parameters, and spleen size on echogram will detect the early stages of MPD and allows diagnostic differentiation of the three primary MPDs (ET, PV, and CIMF) in both JAK2 V617F-positive and JAK2 wild-type MPD patients.

Myeloproliferative neoplasms (MPN) are hematologic malignancies characterized by cellular proliferation of one or more hematopoietic cell lines. Management has been focused on blood count control but addressing relief from symptoms and providing a better quality of life (QOL) are equally important in the care of these patients. The MPN Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS) is used to determine symptoms at baseline and during treatment. Understanding the symptom burden is important in developing a holistic management plan for MPN. Hence, this study aimed to determine the symptom burden and QOL of Filipino patients with MPN. Using a validated Filipino version of the MPN-SAF-TSS questionnaire and the University of the Philippines-Department of Health QOL (UP-DOH QOL) questionnaire, a cross-sectional survey of consecutive patients with MPN from two public and two private tertiary hospitals was conducted. We purposively sampled adults, newly diagnosed or previously diagnosed with polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF). The mean scores were compared with the type of MPN using analysis of variance. Linear regression was done to determine the association of patients' characteristics to the mean symptom burden and QOL scores, while logistic regression was used to determine the association of patient and disease characteristics with the level of symptom severity and QOL. A total of 167 (63 PV, 66 ET, and 38 MF) patients were surveyed from four centers. The mean overall symptom burden score was 24.41 (standard deviation [SD]=18.91) with MF having the highest score at 28.53, followed by PV at 23.75 and ET at 22.67. The majority (80.24%) had a high QOL with a mean global QoL score of 84.92 (SD=16.75). Comparison of individual scores showed bone pain and weight loss were significantly higher in patients with MF compared to PV (p=0.0002) and ET (p=0.032); while pruritus was significantly higher in PV compared to ET and MF (p=0.043). Logistic regression analysis showed female sex and being newly diagnosed (adjusted odds ratio [aOR] 11.22, 95% confidence interval [CI] 2.32-54.25) were associated with high symptom burden while having a controlled blood count (aOR 0.26, 95% CI 0.10-0.71) was associated with low symptom burden and high QOL. The majority of the participants were symptomatic with moderate to severe symptom burden. While no statistically significant difference was seen among the three types of MPN in terms of overall mean symptom score, patients with MF were more likely to have a severe symptom burden while patients with ET had the least symptoms. Despite having symptoms, QOL was regarded as high. QoL was significantly higher among those with PV or ET than those with MF. Our study highlighted the utility of a validated symptom scoring system in determining the symptom burden and who would benefit from pharmacologic/non-pharmacologic symptom management. Results emphasized incorporating symptom scoring in clinical practice and going beyond blood counts in caring for our patients with MPN.

Phenotypic variability within the JAK2 V617F-positive MPD: Roles of progenitor cell and neutrophil allele burdens